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

All right. Good afternoon, everyone. My name is Frank Tang and I'm with the investment banking division at Morgan Stanley. Before we get started, I'd like to read a quick disclaimer. For important disclosures, please see the Morgan Stanley research disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. So thanks again, everyone, for joining us for the fireside chat with Whitehawk Therapeutics. I'm joined today by CEO, Dave Lennon. Dave, great to have you here. Before we get -- as we get started, could you give us an overview of Whitehawk and your strategic focus across your three ADC candidates?

Whitehawk is an ADC company. We in-licensed three ADCs from WuXi Biologics, who we continue to partner with for the further development of each of these assets. There are three clinical stage assets that are focused on various oncology indications. Each of the assets really targets a tumor antigen that has validation. So there's clinical programs that have been run against these targets in the past. But where they're not so competitive yet that there isn't room for us to play and win against these targets. And so we believe we can be first or second to market in each of the tumor targets we're going after. And we're going after a broad range of oncology indications. So lung cancer, gynecological cancers as well as a variety of other tumor types. Ultimately, each of our assets is going into the clinic over the course of the next 6 to 9 months. And we look forward to this time next year when we are fully running three-asset clinical stage company.

Yes, great. Looking -- we're all looking forward to that.

For those who haven't followed Whitehawk from the beginning, can you give us an overview of the WuXi license agreement and that partnership and how these assets were evaluated, so selected by your team. And then what specific features or target profiles you and your team were focused on?

That's a great question. We -- at Whitehawk, we were actually formed as a predecessor company. We were Aadi Biosciences. And we had a product that we were developing that had a failed trial, we ended up selling that asset, it had some in-line sales, to a Japanese pharmaceutical company. That raised $100 million for us. We had some cash on hand, and we went kind of hunting for ways to reinvigorate our pipeline. We spent a lot of time in China, on the ground in China. We had a number of partners we were working with to look for assets across modalities in the oncology space. And we centered on ADCs for a couple of reasons. I think one is they easily translate into therapeutic modalities. And we were very conscious of getting quickly into a clinical stage company again. And then we were looking for really, as I mentioned before, targets that were validated but not inundated. So we find -- picked those targets. And ultimately, we really wanted to make sure we have the best linker payload technology that we could identify. And so we searched through a lot of different platforms. We have tremendous depth of knowledge on the team as well as on our Board in the ADC space that help guide us towards this really unique collaboration between WuXi Biologics and a company called HANGZHOU DAC. Ultimately, they were developing a portfolio of assets in the ADC space. We picked the best three. We brought those into our company. And the licensing deal we did last year, we signed for $46 million upfront. We have about $90 million in development and approval milestones for each asset, and we're really excited to be bringing those forward now.

Great. And any other economic terms of the partnership or future commitments worth discussing?

On the commercial side, so that's pre-approval, the $90 million is pre-approval milestones for each asset that we have left. On the commercial side, it's single-digit royalties and some additional commercial milestones should those be necessary, but that's the full commitment [ we have ].

That's great. Okay. So I guess, please walk us through what differentiates and excites you about each program, how you are prioritizing and sequencing the priority across all three assets?

Yes. I probably should mention what the targets actually are for each of these. So our first program is HWK-007, HWK-007, which is a PTK7-directed ADC. PTK7, super exciting target, really starting to gain some momentum as there's a number of folks working on this target now. This is a target that's broadly overexpressed, probably the most broadly overexpressed tumor target that people don't recognize -- as that. Its scope is on the scale of a nectin-4 or TROP2 or HER2 in terms of patient population, you can potentially address who are PTK7 positive tumors. So this is a really exciting target. That target again has an opportunity within lung cancer, gynecological cancers. The entire GI tract generates PTK7 positive tumors, so multiple opportunities within that. We then have MUC16, so HWK-016 is targeting MUC16, which is the most proliferative or largest tumor target within the gynecological space, super overexpressed. So I'd call it a super target, like a super expressed target. And is cleaved into the circulating biomarker of CA125, just to give you a sense. CA125 is one of the most common gynecological blood-based biomarkers for measurement of progression and response to therapy. And so we're targeting a really exciting target within the gynecological space with that program. And our third program is a CNS-limited protein, SEZ6, HWK-016 (sic) [ HWK-206 ], which is targeting a set of tumors in the neuroendocrine space. So small cell lung cancer and neuroendocrine neoplasias. All of these programs sit on the platform of this really unique linker payload called CPT113. This is a highly stable linker payload. So we have some really unique chemistry that allows us to form paired linkage of bioconjugation of the linker to the antibody. It improves antibody stability and overall stability of the molecule. We think it's the most stable linker payload platform in the industry and should allow us to deliver highly -- high concentrations of ADC to the site of tumor while limiting free payload release in the circulation. And free payload release is what drives side effects within the ADC class, thereby allowing us to have a better risk benefit profile for patients.

Great. Thanks for that overview. Maybe if we focus in on PTK7. Can you go into that more as a target and what excites you about this target? And then why ADC as a modality for this target?

Sure. So PTK7 was a target that has been identified. It was actually originally identified as colon cancer gene called CCR4, PTK7 is more common name. It's a really exciting target because it's an oncofetal pseudokinase, which means that it is highly expressed during early embryonic development and then really minimally expressed in adult tissues. Tumors co-op this target and re-express it over the course, very early in stages of development and it persists throughout metastases. And again, this is a target that is as prolific as HER2, nectin-4, TROP2 in terms of its coverage of potential cancers, and we think a really exciting target. You don't just have to believe us. Pfizer and AbbVie had a program against PTK7 called cofetuzumab pelidotin. That program actually they ended up discontinuing largely due to the side effect profile of that program. But it generated positive data in triple-negative breast cancer, lung cancer and ovarian cancer with some really strong response rates. That was a first generation ADC program, and we really think now with next-generation TOPO-based, really best-in-class TOPO-linker payload platform, we can build on that early data and generate class-leading efficacy and safety.

Okay. No, that's super exciting. Moving on to MUC16 as a target. Could you go into more about this target, what excites you? And then why ADCs...

Well, Mucin 16 is a target that every gyn-onc will know because it is cleaved into the circulating biomarker CA125. And so everyone is very familiar with it. It gets -- it got a lot of attention initially because it also is highly -- you can actually generate antibodies to it quite easily, high affinity antibodies to MUC16. And initially, Genentech ran two programs against this in the ADC space, which actually generated some really positive early promising data. Again, first-generation platform that ran into some problems on the safety side. And therefore, that program was ultimately discontinued by Genentech. And here, we've actually taken additionally an opportunity to rethink about how we're targeting this antigen, excuse me. Originally, Genentech had targeted the circulating and tumor-associated portion of the molecule. And that actually led to some issues in terms of generating antigen sink in the circulation. So their program would actually be cleared from the circulation before it reached the tumor, and they had to dose quite high to generate the effect at the site of the tumor. This led to a lot of side effects and ultimately a discontinuation of the program. Here, we've redesigned our targeting approach for MUC16. And we're actually now targeting the part of MUC16 that is cleaved that is -- sorry, that remains on the surface of the cell after cleavage. And that allows us to bypass all of that circulating CA125. We've coupled that with our advanced linker payload platform. And again, this is the most prolific target within gynecological cancers, 4 to 5x higher expression than the highest expressing FR-alpha, HER2 or other types of cell tumor targets. And we really think, therefore, really one of the most exciting opportunities to address gynecological cancers in the ADC field.

Yes. And what's really exciting about both of these is they're expected to be in the clinic by the end of the year.

Yes.

So what do you expect to demonstrate from the initial clinical readouts and what would you like investors to focus on from these trials during 2026?

Yes. Our view is that it's now incumbent upon ADC players to generate data that demonstrates differentiation early in Phase I. I think everyone is starting to understand that these molecules will work to some degree or not, and that the key issue is what's the therapeutic index of the molecules and how differentiated are they on an efficacy and safety perspective at relevant doses within your Phase I. For us, that means we're translating this into a targeted Phase I strategy that goes after a subset of indications and thereby allows us to generate a sufficient homogeneous population to compare to other ADCs either on the same target or within the same indication. This will allow us to really demonstrate that we have efficacy signals and safety signals that are better or best-in-class. And so our goal is to generate, let's say, for PTK7, initial data in non-small cell lung cancer and gynecological cancers, ovarian and endometrial that can be compared to the FR-alpha classes or the other prior cofetuzumab data. Our belief is that in non-small cell lung cancer, the current bar is 40% or better overall response rate, initial Phase I data. We expect to demonstrate that. And then in ovarian cancers, now we're seeing 50% overall response rate as the bar to be competitive. Again, we expect to exceed that in our -- with our data.

Okay. And then we've covered, obviously, the two that are expected to be in the clinic this year, but you also have SEZ6. Can you talk about that as a target? And what excites you there?

SEZ6 is exciting. You would have seen data yesterday if you're following AbbVie's SEZ6 ADC at World Lung Conference showing initial efficacy in their dose expansion study for small cell lung cancer. Really promising overall response rate in the high 50s, 60% range, but with some significant toxicities on the heme tox side and still a high rate of ILD. So this is a program that really validates SEZ6 as a really promising target for small cell patients. They presented neuroendocrine data at ASCO this year from their Phase I trial. But with a linker payload system that generates a lot of toxicity. And so we really think we can build upon that, both because we're taking an interesting approach to targeting, so we're using a biparatopic antibody that allows us to find multiple sites with on the surface of the cell and recognize and cluster antigen together. That leads to actually better internalization, which should be an advantage for the ADC. And then we have our highly stable linker payload system, which should generate a better safety profile overall. So we really think we can be best-in-class relative to AbbVie in the SEZ6 space. And right now, my view is that AbbVie is kind of leading the pack of the -- sorry, of the SCLC ADCs out there, including DLL3 as well as the B7-H3 class.

Got it. Given that it's expected to enter the clinic next year, do you expect to readout sometime in '26 as well? Or what is the...

Yes. There, we have a much tighter patient population that we're looking at. It's really going to be focused on small cell lung cancer, and our ability to accumulate patients there should go relatively quickly. And so hopefully, we'll also have that data early in 2027, certainly by mid-2027.

Great. All right. To close out, I guess, could you help us with your broad overall pipeline, focus on the most important aspects of Whitehawk that you like investors to keep in mind and focus on for the remainder of this year and into 2026, given all the things you're working on?

Well, certainly, we want to deliver on the milestones of IND filings and starting up our clinical trials, and that should be something that folks pay attention to. I think really exciting in 2026, we'll preview a lot of our preclinical data, which will help give the foundation for a lot of what I'm talking about here. We played that pretty close to the vest so far, just given how competitive the space is, but you'll see some of that data within the course of 2026 and then really getting ready for those data releases in 2027. What I want investors to remember is that we have a best-in-class platform that's going after targets that are validated but not yet inundated, and we really have an opportunity for three shots on goal across multiple different indications in the course of the next 12 to 15 months.

Yes. Great. I mean, it's super exciting, and that's all the questions I had. Any -- should we take any questions from the field?

It's a small group, so we understand if you don't.

No worries. If that's all the questions we have. I'd like to thank everyone for joining us today and look forward to our future discussions.

Thanks.

Thanks, Dave.