Welcome to our last fireside chat for the day. My name is Robert Burns, I'm Managing Director and Senior Biotech Analyst at H.C. Wainwright. I'm joined here by the CEO of Whitehawk Therapeutics. Thank you for joining us today.
Thanks.
Why don't we just dive in? For those who may be unfamiliar with Whitehawk, could you provide a brief overview of the company and its pipeline?
Sure. I'm Dave Lennon, I'm the CEO of Whitehawk Therapeutics. We are an ADC company. We recently relaunched from a predecessor company called Addy Biosciences. This is a transformation where we en-licensed an ADC portfolio from WuXi Biologics. That ADC portfolio targets some really interesting tumor targets that we like to say are validated but not inundated, meaning they have a clear clinical precedent in terms of demonstrating efficacy and their validity as a tumor target, but are not yet so crowded that you can't see a forest for the trees, so to speak. We are moving that pipeline forward. We have three assets in total. Two of them have IND filings in Q4 of this year. The third one with an IND filing in the middle of 2026, which means this time next year we'll be a three-clinical asset company moving forward to data in early 2027.
Okay. Why don't we focus on your lead asset, HWK-007, which is a PCK7-targeted ADC? How should investors be thinking about the potential of this market just broadly?
Yeah, for sure. First, I like to say that, you know, we like the James Bond version, which is HWK-007, for the asset. It is, PCK7 is one of these really exciting tumor targets because it's actually the most broadly expressing tumor target that has really yet to be exploited in the ADC field. It's expressed in a whole variety of cancers, including lung cancer, gynecological cancers, all cancers that emanate from the GI tract. We can treat potentially hundreds of thousands of patients with a therapy targeting this tumor target. This is a target that's really heating up right now in the field, and we're really excited to see ourselves, but a number of other companies launch into the ADC space with a PCK7 directed antibody.
Yeah. You know, some of the preclinical data that you've shown, you know, appears to indicate that HWK-007 shows that it has superior activity relative to the first-generation Pfizer compound.
Yeah.
I note that there are a few other competitors in this space. There are also early stage like you. Xencor is one of them. Day One is another. They're advancing these next-generation ADCs against the targets. I wanted to get your thoughts on those competitor compounds and how HWK-007 is differentiated relative to them.
Yeah. We were very specific about the technology that we en-license. All of our assets are built off of the same technology. While everyone's targeting PCK7, there will be differences out there. The first move is that everyone's moving from the Pfizer precedent molecule, which was an ME or tubulin inhibitor-based ADC. Everyone's really shifting over to the topoisomerase inhibitor-based ADC. All the competition, mainly except for a company called Genmab, is on that topoisomerase-based platform. The reality is that a lot of people think these linkers and payloads are all the same, but there's some really different chemistry that they each utilize to conjugate the topo-1 inhibitor to the antibody. That conjugation process, as well as the chemical structure of the linker itself, can lead to some significant differentiation.
Specifically, one of the folks you mentioned was Day One, who has the MTX13 or Day 301 program now that they have in the clinic. That's built off of a platform from Multitude Therapeutics called the T1000 platform. What we're seeing is now some early data in not that program, but a similar program, a CDH6-directed ADC that's also on the T1000 platform from a company called Omkust. They just reported data in ASCO this year, and you can already start to see how that profile is developing. In that initial data, they showed dose escalation up between 4 to 5 mg/kg. They had some struggles to get beyond that and had to introduce prophylactic GCSF due to high neutropenia rates. That is a severe limitation of that platform overall. We expect to see the same things with Day One.
We've taken our approach to try to design around a lot of those elements to develop really what we think is core to linker technology, which is greater stability of the linker-payload system when it's conjugated to the antibody. That stability is unique to us in terms of what we do. We have best-in-class stability in terms of our free payload release into the circulation, which should limit the type of toxicity you're seeing with the T1000 platform.
Yeah. I know that HWK-007, the IND is supposed to be filed by the end of this year, probably a clinical start first quarter of next year.
Yep.
When we think about the expression profile of PCK7, can you talk about the trial design? Are there any high-yield indications where you think that this approach will be most amenable to your asset? Talk to me a little bit about your overall biomarker strategy as well.
Yeah, it's always the trick here of how to, you want to be able to go broadly with a lot of indications because that's where the opportunity is. Initially in phase one, our view is that strategically we need to demonstrate that the differentiation we're talking about, the stability of our platform, the ability to develop higher potency, better safety is actually pulled through. The way you do that is by evaluating the asset in a homogeneous population. Our phase one will be restricted to a few indications that we're looking to target. There's precedent data for PCK7 in non-small cell lung cancer and ovarian cancers. Those will be two indications in our phase one. The highest expressing histology in tumors is actually endometrial cancer. That'll be the third indication that we include in that.
Our approach is really to target all three of those high-profile PCK7 expressing tumors and develop the data sets around those in a reasonable patient population so that we know we can demonstrate the differentiation we're anticipating and really then earn the right to expand from that position.
Yeah. From a biomarker strategy, obviously when you look at the expression profile, you see this differential efficacy for these various ADCs across IC1, 2, and 3. Are you going to limit the population to just 2 and 3 initially and then maybe go after the low expressors later on, sort of like what INHER2 did in breast cancer?
Yeah, it's interesting. As we get more knowledge about how tumor markers express in different histologies, we think you need to tailor the strategy to the particular indication. When you look at gynecological cancers and PCK7, the expression is generally very high and relatively tight across an entire population. Stratifying won't get you much differences. In those two indications, we really have an all-comers approach. The same is not true in non-small cell lung cancer. We're actually going to get a more distributed PCK7 expression profile across different patients. What we're doing is setting a relatively low threshold for inclusion of those patients by biomarker design, such that we at least eliminate the very low expressors and null expressors of PCK7 in the NSCLC market, which is a huge market. We're cutting off maybe 15% of patients, but we still have 85% of the lung cancer market to go after.
Okay. Why don't we shift gears now to HWK-016?
Yeah, no James Bond name.
No James Bond one for that one. And that's a MUC16 targeted ADC. You know, obviously MUC16 has been gone after by a ton of different modalities, right? You got the bispecifics such as the Regeneron compound. You got cell therapies as well as ADCs. Talk to me about your thoughts around this competitive landscape. How do you see all of these various different modalities potentially being deployed? Let's say that they were to get approved. How do you see that landscape evolving?
Yeah. The reason people go after MUC16 is it's a super high target. It's like a super expressor in tumors, especially of gynecological origin. When you think about just absolute expression, MUC16 is expressed three to five times higher than any other tumor marker out there. It makes this great kind of target for those cancers. That's why so many people have tried to go after it with the modality. It's a bit of a challenging target to go after because of some of the biology around MUC16. MUC16 is actually cleaved and releases the circulating biomarker called CA-125, the most common biomarker utilized by gyn-oncs to measure progression in response to therapy. It's part of RECIST criteria even.
The challenge there has been that sometimes when a modality has been directed against that circulating CA-125 portion of the molecule, it actually gets gummed up in the circulation as opposed to getting to the tumors, and it has limited effectiveness against this target. In this case, like Regeneron actually, in their approach, we've actually targeted the membrane-bound portion of MUC16, so below the cleavage site, so we can bypass all the circulating MUC16 and get right to the site of tumor. That's the first aspect of that. When you talk about modalities, I don't worry so much about different modalities being successful because they all have a different value proposition. TCEs, CAR-T therapy, you're really talking about durability and utilizing the immune response to generate response versus ADCs, which are traditionally really replacing chemotherapy regimen. Both are important to properly treating patients, and we see room for both.
Importantly, there are no other ADCs against MUC16. We are kind of alone in that market and the ability to kind of lead for that position.
Do you see any potential for combinatorial therapies here, especially because you're avoiding the therapeutic sink?
Yeah.
Right. Talk to me a little bit about what sort of agents you think that you would like to combine with, such as the burgeoning PD-1 VEGF class.
Yeah, for sure.
Or even the T1000.
I think one of the interesting things about the profile we have for our linker-payload is we actually do believe there'll be a safety advantage overall. Our payload is not super potent in a way that a pure exatecan payload does, which drives a lot of heme toxicity. That should allow us to think about combinations with chemotherapeutic regimens. We also have attenuated the antibody so that we don't generate things like ILD, which should help us in combination with IO-based therapies. Certainly, as we develop a better understanding of the VEGF, and certainly VEGF as a combination is an interesting combination, particularly in gynecological cancers. Ultimately, we'll see where the VEGF PD-1 bispecifics go, but that'll be obviously an interesting combination agent.
Our goal really is to generate a platform that can really have the safety profile that allows for combination with, you know, what generally in cancer are still relatively toxic regimens overall.
Yeah. I guess let's shift to your last asset, the HWK-206.
Yep.
Talk to me a little bit about the design of this asset, as well as its potential advantages relative to the AbbVie compound 706, which we recently saw clinical data for at ASCO.
Yeah, AbbVie 706, we're really excited about because it's showing some really positive data against SCD6 as a target. 60% response rate in small cell lung cancer, mid-30% in neuroendocrine tumors. Really a great profile for this target in helping treat those patients. We think we have a differentiated approach relative to AbbVie because first on the targeting side of the equation, we use a biparatopic antibody. Biparatopics, you know, haven't been utilized everywhere, but we really think have an advantage in the ADC field by improving specificity of targeting, internalization of the ADC, and hopefully potency overall. That combined with our linker-payload, which we do think has that kind of safer, still potent profile, should allow us to overcome some of the limitations of the AbbVie program, which does have high grade 3 heme toxicity, which could be limiting, particularly in combination.
Yeah.
We really think it's a great target to go after for this subset of neuroendocrine-based tumors, and we think we can have a best-in-class profile.
Given the data set that we saw in SCLC from the 706 program, as well as the slew of ADC data that we saw at WCLC this past weekend, how do you see, when we think about the therapeutic sequencing here, let's say someone were to get the Merck B783 ADC and then the AbbVie compound, where do you see the niche role for your compound? Where do you see it fitting in in that paradigm? There will be a lead time for those agents.
Yeah, for sure. I think the question is twofold. I think one is there's still a lot to understand about can you use topo after topo in some of these conditions and what does that actually look like as you generate slight differences in payload and structure, et cetera. That's one aspect that I think we have to address and understand if there's an opportunity there. More importantly, ultimately treating these patients with more aggressive combination therapy early will be the way that we want to win. I think that we have the best profile to go do that kind of combination work, which will move us ahead, kind of leapfrog, you know, so to speak, in the regimen to get into that earlier second line, first line statements.
Okay, you know, obviously there's going to be a certain cadence of INDs coming up here.
Yeah.
I've been foaming at the mouth.
The team feels like it's all at the same time, but yes, there is a cadence.
I've been foaming at the mouth trying to get more preclinical data from you guys, but I know it's going to be coming after the INDs are filed. Talk to me about the cadence of IND filings here.
Yeah. We have HWK-007 as our first program that'll be in Q4, and then a few weeks later, within Q4, we will be filing the HWK-016 program. Both of those will come before the end of the year. The third program is really mid-2026, a little further behind the other two. We anticipate that we'll start talking about preclinical data over the course of Q1, Q2, first half of next year, really, once we have those studies up and running. We really want to talk about the opportunity for differentiation both from a linker-payload chemistry perspective and from the individual asset perspective.
Okay, that's completely fair, especially given, you know, all the competitive.
It is a competitive area.
I guess my last question is, you know, what is your war chest as of Q2 and what sort of operational runway does that provide?
Yeah, it's a great question. When we set up the company, we really recognized that we needed to get to reasonable phase one enrollment and release of data before we would be able to raise money again in a realistic way. That's really the value inflection point for ADCs. We set up the company with sufficient runway to do that. We have $178 million as we close Q2 to start this quarter. That gives us runway into early 2028. With data in early 2027, we still have a full year of runway ahead of what we think will be some pretty significant data sets.
It is great to hear that you have no near-term cash crunch coming.
Yeah, that's it.
I really look forward to the data coming from you guys. Dave, thank you for being here today.
If there are any questions from the audience, please raise your hand and we'll get you a mic.
Otherwise, we go see George Bush.
All right, thank you so much. Thanks, guys.
Thanks, Matt. Always.