Whitehawk Therapeutics, Inc. (WHWK) Earnings Call Transcript & Summary

Hello. I'm Robert Burns, Managing Director and Senior Biotech Analyst at H.C. Wainwright. And I'm joined today by Dave Lennon and Dave Dornan, President and CSO of -- respectively, of Whitehawk Therapeutics. Dave and Dave, thank you for joining us today.

Thanks, Robert. Thanks for having us.

Awesome. Why don't we just dive in. So for those who may be unfamiliar with Whitehawk, can you please provide a brief overview of the company, its pipeline and its platform more importantly?

Yes, happy to do so, Rob. And to do that, I'll share a couple of slides on Whitehawk today. So we are -- well, I'll start by saying there's some forward-looking statements here, so normal disclosures associated with that. Just to reorient everyone, we previously were known as Aadi Bioscience and went through a transformation that we completed at the end of quarter 1 this year into Whitehawk Therapeutics. Aadi Biosciences had been a small commercial stage company that was working on an mTOR inhibitor. That product was actually sold to a Japanese pharmaceutical company along with the Aadi Biosciences name and brand and is now a wholly owned subsidiary of Kaken Pharmaceuticals. That transaction net us $100 million, which we then, along with a pipe raised for an additional $100 million funded the acquisition and now development of an advanced ADC portfolio. So we're working in antibody drug conjugates against a broad tumor populations with significant unmet need. And we have a 3-asset portfolio that we're rapidly bringing into the clinic over the course of this year -- by the end of this 2025 and early 2026. Whitehawk Therapeutics as an ADC company is very much focused on what we call established tumor biology. So we have utilized tumor markers that are clinically validated and broadly overexpressed and thereby reducing the tumor target risk in our ADC portfolio. Second, we're focused on high potential cancer indications. And so we think we have a broad opportunity to address a whole range of different types of cancers, including lung and ovarian cancer and other gynecological cancers as well as a broad range of GI and other cancers ultimately with this portfolio. And we do really think that this allows us to target broad patient populations that have significant commercial value. We are utilizing in our ADC portfolio a common ADC platform technology, so-called linker payload technology. And this technology has really been engineered for greater stability, which allows for minimal off-target toxicity and an improved therapeutic index, hopefully building on what we've seen in this ADC field already and with the opportunity to deliver best-in-class efficacy in the indications of interest. And I mentioned that all 3 of our programs are currently preclinical, but we anticipate filing INDs for all 3 by mid-2026. So to talk a little more deeply about the portfolio itself. So we utilize, as I mentioned, validated clinical targets. So these are targets where there has been precedent data before. And the first one of those is protein tyrosine kinase 7 or PTK7. This is an oncofetal pseudokinase with broad tumor overexpression, meaning that it's expressed early in embryonic development and then downregulated, but then co-opted by tumors to be overexpressed and utilize that growth and direction that is normally reserved for fetal development in the course of tumor progression. Ultimately, this is a broadly expressed tumor target that had a precedent data from a Pfizer/AbbVie collaborative program called cofetuzumab pelidotin. That showed some really promising efficacy signal, but the platform utilized being first generation had some limitations in terms of toxicity and that program was discontinued. But we look at this target as clinically validated with the opportunity now to come with the next-generation platform, which I'll talk about in a second. The second program is against Mucin 16. Mucin 16 is a really interesting tumor target because it's overexpressed in cancers of female origin. And it is also then cleaved into the circulating biomarker called CA125. So MUC16 is the originating molecule for the circulating biomarker CA125, which in gynecological cancers is a really important marker for clinical progression, widely utilized within the gynecological community to monitor cancer in those settings. We have a really interesting approach in targeting this molecule and also building upon precedent data the same way we are for HWK-007. With HWK-016, there was a Genentech program that showed some really promising efficacy signals in ovarian cancer. But again, that program was discontinued due to side effects associated with first-generation molecules. And moving to our advanced platform, we think we can build on that efficacy signal and modify the safety profile for this target. Then our third program is seizure protein 6 or SEZ6. SEZ6 is a CNS limited protein that is often upregulated in cancers of neuroendocrine origin. These are cancers like small cell lung cancer and neuroendocrine neoplasias. So HWK-206 is a targeted molecule, which is -- can specifically target these types of tumors and potentially lead to better efficacy for these patients. There's currently an AbbVie program, which also targeted to this molecule, which is showing some promising early efficacy signals in small cell and neuroendocrine tumors, and we think we have an improved approach to build upon that initial data with a best-in-class profile for this target. Ultimately, all 3 programs are built off of the same linker payload platform, what we call the CPT113 platform. This was part of our in-licensing strategy for this platform and has a unique architecture that provides for high linker payload stability and allows us to deliver a novel TOPO1 isomerase inhibitor payload, so-called advanced payload opportunity with -- for each of these targets. Importantly, this platform has been tested in humans with 2 programs developed by our partner in China, DXC006 and DXC1002. And these are platforms that are -- sorry, these are programs that are currently in Phase I dose escalation in China and demonstrating some early positive signals in efficacy and safety. Ultimately, our approach with our platform is really to engineer an improved therapeutic index for the ADC class. We have a proprietary TOPO1 inhibitor payload, which really minimizes off-target effects and supports that higher therapeutic index that we're trying to generate with this next-generation approach. It's a highly stable but still cleavable linker system. And I think that's really important to note is that this kind of linker construct allows for low free payload release in circulation and really target release at the site of tumors and accumulation of the cytotoxic agent at the site of tumors. And ultimately, there are some tricks in chemistry that we haven't fully disclosed yet, but really allow us to optimize the DAR ratio for these molecules and enhance the PK profile, which supports longer half-life of the ADC and ultimately optimal dosing for patients. Altogether, these effects we're trying -- what we're trying to do is drive that improved therapeutic index, which is shown on the right. So first-generation ADCs have been really promising in their delivery of efficacy, but have -- multiple of them have faced many limitations due to this concept of low therapeutic index, meaning that their minimally effective dose is very close to their maximally tolerated dose and thereby, patients develop too many side effects for these molecules to be utilized regularly in patients. Ultimately, what we're trying to do with next-generation linker payload constructs is widen that therapeutic index, lower the minimally effective dose, so more potent molecules while increasing the maximum tolerated dose, meaning that we have a higher safety threshold. And that's the promise of our CPT113 platform and each of the molecules that Whitehawk is trying to develop. As I mentioned, we have 3 programs that are targeting -- that are currently in preclinical stage against each of these targets. And we plan to deliver the first program, HWK-007 into IND in Q4 of this year. Shortly following that by the end of the year is HWK-016 and then by mid-2026, HWK-206. So we really have 3 shots on goal here quickly into the clinic over the course of the next 12 months. As I mentioned, each of these molecules has precedent data being generated or that has been generated by prior molecules in various indications. But each of these markers is also expressed in other tumors that haven't been tested yet, giving each of these programs a broad expansion opportunity to address a range of indications where there's still significant unmet need for an advanced ADC program. Ultimately, we believe we have a great value proposition to make a transformative impact for patients. As mentioned, we have clinically validated broadly overexpressed tumor targets that we're coupling with an advanced ADC linker payload technology that really improves that therapeutic index opportunity. These are all high potential indications, and we believe we have the opportunity to be first or second to market in each of these spaces with a high ability to compete from a differentiation perspective. And I'm sure we'll talk more about that today. We mentioned where we're targeting our IND submissions already, and we have the team to execute upon that folks like David Dornan, who joins me today as our CSO, with a deep ADC experience and multiple IND and clinical filings to date. And ultimately, we -- sorry, ultimately, we anticipate our capital position to allow us to execute into 2028, which gives us sufficient runway to generate early clinical data from each of these programs through dose escalation and early expansion in our Phase I trials. So that's where we are today, Rob, at the high level and happy to kind of go deeper and talk about questions you may have.

Awesome. Thanks, Dave, for that overview. I guess before we get into your pipeline assets, one of the things that I find intriguing is that there are 2 of those hangs out DAC programs, DXC006 and DXC1002, they're already in Phase I development over there in China. And DXC006 is anti-CD56, CPT113 targeted ADC. But I think investors are paying attention more to 1002 because it's a TROP2 targeted ADC. And when we think about that landscape, obviously, you got Dato-DXd. And that initial data set, I think, can be extremely derisking for your own portfolio assets. So is there any color as to when we might see initial data for that compound from your partner in China?

Yes. It's a great question, Rob. And I would say that HANGZHOU DAC has been an excellent partner to us. They've been working for over a dozen years on various ADC platform technologies. This is the most advanced platform technology that they've developed. And certainly, that data from DXC006 or 1002 could be highly informative to how the platform performs overall, as you say. It is another company. It's not our programs, so I wouldn't comment on potential data release that they might have in plan. But certainly, we will look out for that, and that will be informative to what we might expect to see from our programs.

Okay. That's completely fair. Why don't we then focus on your lead asset, HWK-007, it's a PTK7 targeted ADC. From a broad high-level overview, how should investors be thinking about the market opportunity for this compound? Because it seems to be that PTK7 is widely expressed across a variety of solid tumors.

Yes. I think that's the real opportunity here with PTK7. What I would say, first and foremost, is it is one of the most broadly overexpressed tumor targets that's available. And so you can think about it very much in line with the commercial opportunity of like a TROP-2 or a nectin-4 or a HER2 in terms of its potential to impact a lot of patients because they do have expression of this marker on up to 60%, maybe 70% of all cancer patients at some point in their disease. The other point we really like to think about with PTK7 is that when it is expressed, it's often expressed at a moderate to high level. And that's really important because that consistency of moderate-to-high expression, we know can potentially or at least we know from other markers can potentially lead to a greater chance of response from patients. And that's another dimension of PTK7 we think is really important is that, that moderate-to-high expressing patient is one who will benefit potentially from a PTK7-directed ADC. So when we think about this, those are really 2 important aspects of the overall opportunity. In the short term, we do want to make sure, though, that we also say, well, where do we have data. And we have data in lung cancer, in ovarian cancer and in triple-negative breast cancer from Pfizer, AbbVie's prior program and that already establishes an opportunity and a huge opportunity from a commercial perspective, let alone where else we can go in terms of GI cancers and other cancers down the road.

Yes. So obviously, I would assume then that those are going to be the 3 high-yield indications that you're initially going to go after considering it's so derisked. And then there are some other high-level expression ones like prostate, head and neck. Those will be secondary, if I see what you're saying correctly.

Yes, I think that's right. I think we haven't decided exactly which indications will be a first focus. But we do believe that the clear opportunity here is to demonstrate the differentiation from the precedent molecules and the opportunity to build on those, which will allow us to translate the impact of our platform and extrapolate that into further indications. It's kind of a right to play kind of approach that we like to take, which is that we validate the potential of the molecule on those precedent indications like lung cancer and ovarian cancer, and then we build in the future into other high-expressing -- PTK7 high-expressing cancers.

Okay. That's completely fair. One of the other things that I noticed from the preclinical data that we've seen is that it appears to indicate that has superior activity relative to that first-generation Pfizer compound. But I also note that there are 2 other competitor compounds, one coming from Zymeworks and the other one from Day One Pharmaceuticals that they call next-generation ADCs. So I want to get your thoughts on those competitor compounds and how HWK-007 is differentiated from that?

Yes. The -- so HWK-007 has some, we think, some pretty great activities. And maybe I'll turn it over to David at this point to talk a little bit about the profile of HWK-007 from a potency and safety perspective and what we think the potential is there. And then I'll come back and comment a little bit on the competitive landscape.

Yes. No, happy to do that. So as Dave mentioned, right, the platform perspective, right, so we have this aspect called the carbon bridge site-specific conjugation. And Dave flashed up a figure that basically showed a carbon bond link in between 2 essentially -- they were just linkers to payloads, if you will. But what that essentially chemistry does is it enables the stability of the linkers to be conjugated on to the antibody. And importantly, there's other aspects to it that we haven't described publicly at this time, but there were things that we have done to improve hydrophilicity, which, of course, topoisomerase inhibitors are generally hydrophobic in nature. And so you have to do a few different chemistry plays to try and increase the hydrophilicity of it. And so we've done that. And then also, we have a cleavable peptide sequence that we believe is fairly novel for our field. So all in all, as Dave said, the goal of being able to optimize those 3 aspects. So basically the cleavability of the linker, the hydrophilicity as well as, of course, the stability of the conjugation using this carbon bridge, essentially, those 3 things are what are key to basically having an ideal PK profile, enhance the tolerability and importantly, efficacy because now you have more available ADC to get to the tumor. And then as we've mentioned before, right, it's all about how do you enhance the therapeutic index. But I will say that even so like bystander effect, which is, of course, the ability to kill target antigen negative cells that are nearby target antigen positive cells like in the tumor, that is also something that this platform has been optimized as well to accomplish. So that's why we believe our platform has the greatest potential. And then Dave, if you wish I can just allude a little bit on the competitor molecules if you want...

Yes, go ahead. You start and I'll add...

I'll start and you can then -- so like you mentioned Day One. So Day One uses essentially the Multitude platform, and they have -- their play is something called a T1000 moiety. And what there -- it's a self-immolative part of the linker, if you will. They essentially -- they're using it to try and overcome the hydrophobicity of exatecan. And it's a very, very smart chemistry play. Their platform uses regular cysteine conjugation. And so with that in mind, traditional cysteine conjugation does have limitations too. You can have, of course, deconjugation caused by retro-Michael reactions and things like that. So you may get some payload that could essentially fall off. But the reality is, sure, it's a smart platform. It's good what it is, as it says, it's advertised what it does. But from -- relative to our platform, we've got more -- we would say we have more optimization involved from end to end, from antibody all the way from linker to payload. And then the -- I think you mentioned Zymeworks. So Zymeworks, they actually were one of the few as well that actually tried to find their own exatecan-like molecule. And their payload itself is dialed back on potency. They're essentially enhancing hydrophilicity. And I think their idea was, of course, to just help improve PK, plasma stability and such like. But they -- from what we know from their molecule, which was the biparatopic, one was being proposed at AACR. And you know from -- obviously, we're big fans of biparatopics because of our SEZ6, and we believe that they potentially can enhance internalization. And that was seen in Zymeworks AACR poster. But just there was some curious data that they had at AACR that looked like it did not really enhance in vivo efficacy for whatever reason, it was very minor increase relative to like a monotopic antibody. But nonetheless, that's just hopefully a high-level comparison across the platforms.

Yes. I certainly agree to that.

Yes, Rob -- so David, I think that's right. The thing I would like to step back and say is PTK7 is a huge space. So there's multiple -- we're not competing for a single indication or a subset of patients. There's lots of opportunities for potentially multiple parties to be in this space. As David points out, we think there are limitations to the platforms that are involved as being somewhat just maybe earlier versions of that next-generation wave, not fully optimized in the right spaces. I think one of the things I would point out, right, is the T1000 platform from Multitude is actually being utilized across a number of programs. And I think we've seen the first clinical data off of that platform from OnCusp recently at ASCO. And so some of the things that we noted that are just questions in our mind is, I think, first is kind of maximally tolerated dose on that platform seem to be limited at around 5 mg per kg. And you also saw some intriguing safety cases of ILD in the ovarian population, which we thought was kind of unusual. Now maybe it's a one-off. It's only a couple of patients, but that was a little bit striking in that patient population. And so that may or may not carry through to other platforms, but it's -- there will be other data to read through on the Multitude T1000 platform. And then similarly on Zymeworks, they've had a couple of different shots with that Platform They've taken forward and later discontinued. I think there was a biparatopic HER2. I think there was a NaPi2b. And so there's probably learnings, I think, that folks could draw from kind of the progress of those prior molecules in the Zymeworks platform about where their therapeutic index may land in terms of the approach they take. And so overall, what I would say is that I think there's -- if you think about step changes in that therapeutic index opportunity, certainly, both of those molecules improve upon first generation, but we don't think they're fully optimized to take advantage of that really higher -- that real benefit of the risk-benefit opportunity that CPT113 platform that we've in-licensed provides.

Yes. No, no, that makes a lot of sense. And I'm definitely curious to see as to how the data sets are going to evolve over time. One of the other things that I wanted to sort of touch base on, obviously, when we looked at the first-generation PTK7 targeted agents data set, obviously, we saw this massive differential between the objective response rates in the moderate to high population and the low population. And we saw that as well in the first-generation folate receptor alpha program, right? Now as we look towards the second-generation folate receptor alpha programs that are coming about, some of these assets don't seem to have as much of a delta between objective response rate in moderate to high versus low. So I wanted to get your thoughts as to how HWK-007 will -- what it will demonstrate in that lower-expressing population. I don't know if you've ran that preclinical experiment, but I wanted to get your thoughts there as well.

It's a great question, Robert. I think there's a couple things. Biomarker expression is actually much more complicated than we make it out to be, especially since often what we're measuring is IHC-based analytical methods, which have a lot of variation and are quite -- and are uniquely tuned for each tumor target, which -- what that means is a high-expressing PTK7 population versus a high expressing MUC16 population may be very different in terms of the absolute expression of the marker because they're all graded on a relative scale. And the IHC is tuned to generate kind of that differentiation. And so you can have markers that say they're high, medium and low, but the actual variation may be very small. You can have markers that are high, medium, low and the variation is very high. And you can also have them at different levels of expression, right, in terms of absolute expression overall. So I think it's very hard often to compare from marker to marker without kind of normalizing for all of those factors of that. Now with all that said, getting off the soapbox of why IHC might not be the best way to think about this. It is the situation we have today. And certainly, for PTK7, we do see that gradation across expression, at least in the early program. We'll see in the clinic what that means for our molecule. We do believe that our antibody starts with higher affinity or really a slower off rate, which should improve internalization and particularly also in low expressing cells, which may be beneficial ultimately to the efficacy that we see in those low-expressing patients, but that's still to be proven. I think what is important here is also to think about the long-term prospects of how we think about expression. And ultimately, my belief is that doctors and our belief at Whitehawk is that doctors are going to want to find the drug that is most likely to give their patients a response. And so expression profiling for tumor markers will start to become standard practice in the future as more ADCs and other modalities that utilize tumor markers become more prevalent in the regimens of choice for different indications. And we think that will drive is a situation where doctors are going to select the molecule they use not based on whether it's broadly applicable but whether it's specifically applicable for that patient. And so we do think that biomarker expression and characterization of biomarker expression throughout a clinical development program is really important and that molecules that try to go for all comers and dilute their efficacy on their low expressers actually are hurting themselves in terms of their development profile overall. That's our view. And I think one also held by just common sense, but also physicians who say, "Hey, I want to give my patient the best chance." And if you're a high PTK7 expresser, you're more likely to respond to a PTK7 ADC.

Yes. No, that's completely understandable. And since 007 is going to be in the clinic later this year, talk to me a little bit about the trial design, whether you're going to eliminate that low expressing population, whether it's going to be going to be the moderate to high. And what are the sort of go/no-go signals you're going to be looking for to advance that program into later phase development?

Yes. So at Whitehawk, we're very disciplined about our capital allocation, but also about how we think about moving programs through milestones. Our approach, as I mentioned, is one where we think the best thing we can do to generate differentiation is show that our molecule performs better in indications where we have precedent data and where there are clear competitors. And so our initial Phase I trial for PTK7 is likely to be focused in lung cancer and other gynecological -- ovarian being one area of cancer where we have data already and where we have a number of competitors to demonstrate kind of the therapeutic bar that we expect to see. Typically, when we look at lung cancer today in biomarker-positive patients, we're seeing kind of 40% as the minimal bar for differentiation. We believe that's achievable with PTK7-directed approach. And in ovarian cancer, that's often 50% now or higher overall response rate and some of that initial data. And so in terms of our Phase I design, we will be very focused on generating information in those patient populations that prove out that hypothesis and demonstrate an ability to kind of beat the bar from an efficacy perspective and be competitive. And if we don't achieve that, then we need to pivot and move on to other things. I think biomarker expression will be part of that strategy for sure. I think there's still -- we're still working through a view on the data available to say what the right cutoff might be for that. And that may be something we do retrospectively in the context of a Phase I trial, where we're still exploring exactly where this can be -- the product can be most effective at and at what expression level that happens.

Okay. Last question for me on 007. I don't know if you've disclosed this already, but what is the DAR for that compound?

David, do you want to talk about our DAR approach?

Yes, sure. So the DAR of that molecule is 6, so that's what we optimize just based upon numerous parameters preclinically as well as manufacturing. And DAR optimization is always an interesting topic that we can probably talk about, but I know you have other questions. But certainly to say that methodical methods were put in place and criteria to select the optimal DAR for the target.

Okay. All right. Why don't we shift gears now to 016. Obviously, MUC16 is -- it's a highly sought after target. Several different approaches have been advanced, including bispecifics, cell therapy, other ADCs, even monoclonal antibodies. So I wanted to get your sense as to how you view this competitive landscape with all of the different modalities that are going after this target.

Yes. It's a great question. I think that MUC16 is one of those targets because it was a circulating biomarker in the blood, CA 125, has been around for quite a long time, and people have thought about how to utilize it as a therapeutic moiety or target. When we think about oncology modalities, I do think that there's plenty of opportunity for competitors when we think about immunology-directed approaches like a CAR-T or bispecific versus cytotoxic-driven express -- approaches like ADCs versus potential other kind of combinations in the future. And there's clearly play for both. And certainly, often immunologically based approaches provide that opportunity for durable responses that all patients would like to achieve. But the immune system doesn't always cooperate in terms of generation of that. And then you do need cytotoxic agents. And I think one of the wonderful things about ADCs is that opportunity to replace systemic dumping of chemotherapy into a patient's blood for treatment of their cancer with like highly targeted and postal ZIP code directed cytotoxic therapy to their tumor. And the reality is that chemotherapy is still the most utilized form of treatment for patients with cancer. And so ADCs have a huge opportunity to replace that regardless of what happens with other areas and different modalities that might target the same moiety in this case, MUC16. So that's the first point I would make. I think there's plenty of opportunity between modalities. I think the second thing I would say about MUC16 is that the problem with a lot of MUC16 approaches in the past has been that they targeted that CA 125 circulating portion, which made actually the execution against this target more complicated than it needed to be because biological molecules, you kind of can get your molecule stuck in the blood and not get to the tumor, which happened, we think, with the prior Genentech program in the ADC field. Our approach is a targeted one. It's one being utilized by a couple of other players, not in the ADC field, but it is an approach which targets the membrane-bound portion of MUC16. So it's smartly designed to find an epitope that is below the cleavage site of the protein on the surface of the cell, thereby bypassing all of that circulating MUC16 or CA125 and getting -- still getting to the tumor onto an epitope that is highly present there. So we think this approach bypasses a lot of -- or has been developed based on an understanding of a lot of precedent data for this target and it's really promising because now we can combine that biomarker circulating in the blood to identify patients who are enriched for MUC16 expression on the site of their tumor, but bypass the circulating CA125 to get our drug to the site of the tumor. Interesting thing about MUC16 is for some patients, it's the most highly -- when we talk about absolute expression, it's actually one of the most highly expressed tumor targets that is out there, higher than HER2, which is also a highly expressed tumor target in certain types of cancers and really has that potential then to be a very effective target for a lot of patients.

Yes. I completely get what you're saying there. I guess one of the things I'm sort of curious about as well is the data that we saw from the Regeneron compound 4018, obviously, it's being evaluated in Phase II in combination -- either as monotherapy or in combination with an anti-PD-1. So I want to get your thoughts on that program specifically. But also, how do you -- let's assume that the Regeneron compound comes to market, how do you see the potential sequencing? Do you think that you could give a MUC16 targeted ADC post this MUC16 bispecific. I wanted to get your thoughts as to how you see that landscape specifically playing out.

Yes. I think the question that comes up, and David may have also had some comments on this, is what is the mechanism of progression on a certain -- on these tumor-targeted therapies. Generally, the data that we're seeing consistently shows that it is not loss of tumor marker that drives progression, it is loss of or ineffectiveness of the relevant payload or relevant modality. So in the case of Regeneron, if their T cell target -- T cell engager moiety progresses or doesn't work in that situation, we wouldn't expect that to lead to downregulation of MUC16. So certainly, MUC16 targeted agent like ADC could still come after that and be effective, at least in theory, that obviously has to be borne out in practice. But that's -- consistently what we're seeing so far is that patients progress mechanistically against the modality, not necessarily due to loss of target. But David probably has more experience with this than I do. So any comments, David?

Yes. I mean I do think that like I view them like their orthogonal mechanisms, right? So obviously, Regeneron molecule is bringing in obviously CD8 T cells in theory to the tumor microenvironment to try and obviously kill the tumor. And if you -- even when you think about sequencing them or how you could do it, the fact that they're orthogonal, you could consider them, well, you don't have to be too far apart to give alternative different treatment options. And so like coming in with, we'll say, like a TOPO inhibitor in any other IO right now, like a PD-1, for example, with Regeneron was combining with PD-1, then there's data to support that there's a synergy there with immunogenic cell death caused by obviously, the topoisomerase inhibitor from the ADC. So I think all options are on the table there when it comes to being able to combine potentially down the line, obviously, not at the same time, but certainly, as you said, sequencing, certainly on topic given the orthogonal mechanism.

Yes. So one of the things that you mentioned before with regard to 016 or MUC16 in general is this potential for an antigen sink. How exactly does 016 actually mitigate that? How do you get around that problem for that cleaved MUC16 that's in the blood?

Yes. It's a great question. One of the things that was seen in the Genentech program or hypothesized in the output of that program. So what happened with that program is you really saw -- it was an MME-based payload. And what you saw is a lot of -- a highly effective molecule at about 5.2 mg per kg which for an MME-based payload is actually a very high dose. Typically, doses are utilized are lower than that. And so one of the hypotheses that Genentech had was that actually, they had to go to higher dose because so much was getting cleared in the blood, like half of that amount was getting cleared in the blood. And really, their effective dose was closer to [indiscernible] 2.4 or 3 mg per kg when you think about what was getting potentially cleared through circulating CA125 because there is a lot within the [ blood ]. So what we've done with the HWK-016 molecule is actually pick an epitope, which is below the cleavage site of the molecule. And so if you think about the [indiscernible] sticking out of the cell, it gets cleaved at some point along that on the extracellular side of the cell, and our epitope is below that cleavage site. And so the -- and we've shown this in vitro and in vivo in animal models, there is no binding of HWK-016 to the CA125 portion of MUC16. And so that allows us to bypass circulating CA125. And when we've tested that in animals that have been implanted with high shedding tumors, we can demonstrate that the MUC16 antibody doesn't work, and we can demonstrate that our antibody works both in the context of our CPT113 platform, but also using the Genentech -- prior Genentech platform. And so there's really an opportunity here to -- for the antibody just to be much more targeted to the site of tumor and be much more effective in those patients who are having high circulating CA125, which is the vast majority of ovarian -- progressive ovarian cancer patients and a lot of other gynecological cancers.

Okay. So this Phase I program that you're going to initiate by the year-end, I'm assuming it's going to be targeted solely at the gynecological cancers. Any thoughts as to targeting other MUC16 target tumors because it's not just ovarian and other gynecological cancers that you could go after with this target. So I want to get your thoughts there.

Yes. MUC16 is a really interesting molecule. It is overexpressed in a number of other cancers, particularly pancreatic cancer and some non-small cell lung cancers. There's large portions of patients who have that. I think given that -- but at the same time, a lot of those patients don't express high-circulating CA125 and that may be tumor dynamics, et cetera. And so part of our strategy here is to prove out the molecule is highly potent in those gynecological cancers to demonstrate that we have that before we take on the risk of going into these other unproven spaces and difficult-to-treat pancreatic cancer being a very difficult cancer to treat. So it will be a second step in our program, but clearly an excellent expansion potential for those patients who have MUC16 positive cancers.

Okay. Why don't we shift to the last asset within your portfolio, at least the last asset that we know of within your portfolio and this is a biparatopic. This is your first biparatopic compound that you're actually going -- that you're actually developing. So I want to get your thoughts as to the biparatopic approach in general, whether we could potentially see more biparatopics in your portfolio. Where do you think a biparatopic is best suited versus the monotopic ADCs?

Yes. It's a great question. There's a lot of science behind this. So maybe I'll turn it over to Dave to talk a little bit about his thoughts on this approach. It's definitely one of his favorites so.

Most things in science, right, should be designed on like fit for purpose, right? Why do you need one tool versus another, right? And so biparatopic versus monoparatopics fit in that kind of category, right? So ultimately, it just depends upon -- a lot of it depends on your target antigen, right? Because sometimes binding one site on a receptor is more than sufficient to drive internalization. And sometimes when you add another binding site, it actually doesn't increase much. Whereas in our case for SEZ6, this is a case where actually when you do bind 2 binding sites with 1 antibody then you actually result in significantly enhanced internalization. So I think like everything else in biology, as long as you are designing it for what the intended purpose was and what you're trying to achieve, so in this particular case, as I said, for SEZ6, we identified that if you bind 2 independent sites on the molecule, you get greater internalization. But that's not the same for every target. Every target behaves differently. So that's why you just got to design what you're trying to do.

Yes. No, I completely agree with you there.

And I think to build on that, what we've seen is that, that translate -- that needs to translate into better efficacy. And the first step of that is showing that in vivo. And what we can consistently see is this antibody performs better than the AbbVie antibody in the preclinical setting when conjugated to the same payload structure. And so we think it is at least in the initial step demonstrating that advantage. And now we'll look for that to translate either into better efficacy for patients in the clinic or better safety because there is also that potential to be a safer drug with a biparatopic approach utilizing lower doses.

So obviously, we saw the ABBV-706 data at ASCO. So I wanted to get your thoughts on it, both from a small cell lung cancer perspective but also a neuroendocrine tumor perspective.

Yes. I think both are just super exciting. I mean the small cell data initially they showed was 60% ORR in that initial data, very highly potent molecule or tumor target in a very high unmet need indication. And so that, we think, is very exciting to validate this tumor target and provide a starting point, we think, for where we can build on and improve the overall therapeutic profile for those patients. And then recently, the neuroendocrine data, I mean there's really nothing for neuroendocrine patients.

Other than radiation therapy...

Yes. I mean -- and that's if you can find their tumor, right?

Yes.

So this is really an opportunity, we think, to -- there was a 40%-ish response rate that you saw with that, which is really a great response for those patients. And again, we think data that we can build on with our approach -- with an improved approach in terms of targeting and the platform approach we have, which we think has certain advantages.

So I've seen the in vivo preclinical data where you show greater binding as well as internalization relative to the AbbVie compound. I didn't see any efficacy data there, however. So have you ran that head-to-head experiment against ABBV-706 from an efficacy in vivo perspective in xenograft models?

What I can say is what I said before is that when we conjugate the -- we really look at antibody performance as kind of the first differentiator. And certainly, when we look at antibody performance when conjugated to the same payload, we see greater efficacy in the approach that we've generated. Ultimately, AbbVie has -- 706 has a proprietary linker construct and novel payload, which is utilized both for their 706 molecule, but also their 400 molecule, which just recently was approved in c-MET-driven cancer. And certainly -- so we can't compare those head-to-head per se. But we're really confident, at least in our targeting approach being of improved -- an improvement upon that molecule. And ultimately, we'll see where the clinical data sets out when we compare across platforms.

Okay. When we look ahead, obviously, we got these INDs sort of coming back to back to back, right? First one is going to be 007, then 016 and then obviously, 206. So by middle of next year, pretty much all your programs are going to be in the clinic, right? So talk to me a little bit about your war chest and what sort of operational runway that provides as well as when can we expect to see additional preclinical data for these agents?

Yes, it's a great question. Rob, we've played things pretty close to the vest in terms of releasing data publicly. It is a hypercompetitive space, and we know people would love to see all the data all the time. But our first goal is to get these programs into the clinic, get cleared with the FDA to start running our clinical trials. And then we will disclose more data. And so you can expect to see more data coming in 2026 from a preclinical perspective and details on our plans -- for more detailed plans around our clinical trials and biomarker strategy, et cetera. So that's the kind of the timing when you'll see that information coming. I think stepping back to the war chest question, the company started Q2 with approximately $185 million in pro forma cash in the bank to prosecute against -- specifically against these assets after we completed all of the transactions to sell our prior asset and in-license this portfolio. We believe that gives us runway into early 2028. And our goal is really to generate a bolus of data that gives clarity around the potential differentiation and performance of each of our molecules before we go back to the market for additional monies to think about further development. We do believe that's probably an early 2027 event that we would think about release of data. But because we don't want to drip data out per se, we want a clear kind of view on what these products can do in a reasonably sized patient cohort.

I think that's an extremely judicial measure, especially because we've seen time and time again smaller biotech companies leak data out in increments and then they get hammered on the market, right? Just because there is so many ...

It always seems to get worse somehow, right? The first one is great and the next ones aren't so great. So we'll just come with the answer, hopefully.

No, I hear you. Last question for me before I let you guys go. Obviously, it seems like there's a lot of potential behind this platform, right? And there's a lot of viable targets that you could go after. So is there anything else under the hood that we might not know about yet? And when could we potentially find out?

Well, Rob, that's not a question I'm going to answer today, unfortunately. Just to say, we -- it's a highly competent and capable team. We have a great group of investors behind the company, and we're continuing to think about how we can augment our approach while being judicious and focused on the execution that we have in front of us. Importantly, any one of these molecules shows positive efficacy, and it's really a positive for us, and we have 3 opportunities to do that. Do we need more? Maybe, maybe not. We'll come to that bridge when we cross it -- cross that bridge when we'll come to it I guess is what I should say...

Well, I certainly appreciate you guys taking the time with me today and for everyone else who's watching this. So Dave and Dave, thank you again.

Rob, thank you so much, and appreciate Wainwright hosting the call today.

Awesome. Sounds good, gentlemen. Thank you so much.