If you have any questions, please reach out to your Morgan Stanley sales representative. 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. As we get started, could you give us an overview of Whitehawk and your strategic focus across your three ADC candidates?
Sure. Whitehawk Therapeutics is an ADC company. We license the 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. There are 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. We believe we can be first or second to market in each of the tumor targets we're going after. We're going after a broad range of oncology indications, including 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 six to nine months. We look forward to this time next year when we are a fully running three-asset clinical stage company.
Yeah, 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 Biologics license agreement and that partnership and how these assets were evaluated, selected by your team? What specific features or target profiles you and your team were focused on?
That's a great question. At Whitehawk, we were actually formed as a predecessor company. We were Addy Biosciences, and we had a product that we were developing that had a failed trial. We ended up selling that asset. It had some inline 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. We centered on ADCs for a couple of reasons. I think one is they easily translate into therapeutic modalities. We were very conscious of getting quickly into a clinical stage company again.
We were looking for really, as I mentioned before, targets that were validated but not inundated. We found, picked those targets. Ultimately, we really wanted to make sure we had the best linker payload technology that we could identify. 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 helped 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. We're really excited to be putting those forward now.
Great. Are there any other economic terms of the partnership or future commitments worth discussing?
On the commercial side, 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. That's the full commitment we have.
That's great. OK. Please walk us through what differentiates and excites you about each program, how you are prioritizing and sequencing the priority across all three of them.
Yeah. I probably should mention what the targets actually are for each of these. Our first program is 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 Trop-2 or a HER2 in terms of patient population you could potentially address who are PTK7 positive tumors. This is a really exciting target. That target, you know, again, has an opportunity within lung cancer, gynecological cancers. The entire GI tract generates PTK7 positive tumors, multiple opportunities within that. We then have MUC16. HWK-016 is targeting MUC16, which is the most proliferative or largest tumor target within the gynecological space, super overexpressed.
I like to call it a super target, like a super expressed target. It's cleaved into the circulating biomarker 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. We're targeting a really exciting target within the gynecological space with that program. Our third program is a CNS-limited protein, SEZ6. HWK-206 is targeting a set of tumors in the neuroendocrine space, small cell lung cancer and neuroendocrine neoplasms. All of these programs sit on the platform of this really unique linker payload called CPT113. This is a highly stable linker payload. 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 high concentrations of ADC to the site of tumor while limiting free payload release in the circulation. 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 the 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. PTK7 was a target that has been identified, was actually originally identified as a colon cancer gene called CCR4. PTK7 is the more common name. It's a really exciting target because it's an oncoprotein tyrosine kinase, which means that it is highly expressed during early embryonic development and then really minimally expressed in adult tissues. Tumors co-opt this target and re-express it over the course very early in stages of development and persist throughout metastases. This is a target that is as prolific as HER2, Nectin-4, TROP2 in terms of its coverage of potential cancers. 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.
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. 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.
OK. 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 ADC?
Yeah. MUC16 is a target that every gynecologist will know because it is cleaved into the circulating biomarker CA125. Everyone's very familiar with it. It got a lot of attention initially because you can actually generate antibodies to it quite easily, high affinity antibodies to MUC16. Initially, Genentech ran two programs against this in the ADC space, which actually generated some really positive, early promising data. First-generation platform that ran into some problems on the safety side. Therefore, that program was ultimately discontinued by Genentech. Here, we've actually taken additionally an opportunity to rethink about how we're targeting this antigen. Originally, Genentech had targeted the circulating and tumor-associated portion of the molecule. That actually led to some issues in terms of generating antigen sink in the circulation.
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 discontinuation of the program. Here, we've redesigned our targeting approach for MUC16, and we're actually now targeting the part of MUC16 that remains on the surface of the cell after cleavage. That allows us to bypass all of that circulating CA125. We've coupled that with our advanced linker-payload platform. This is the most prolific target within gynecological cancers, four to five times higher expression than the highest expressing FR-alpha, HER2, or other types of cell tumor targets. We really think, therefore, really one of the most exciting opportunities to address gynecological cancers in the ADC field.
Yeah, you know, what's really exciting about both of these is they're expected to be in the clinic by the end of the year.
Yeah.
What do you expect to demonstrate from the initial clinical readouts? What would you like investors to focus on from these trials during 2026?
Yeah. Our view is that it's now incumbent upon ADC players to generate data that demonstrates differentiation early in phase one. I think everyone's 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 one. For us, that means we're translating this into a targeted phase one 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.
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 in initial phase one data. We expect to demonstrate that. In ovarian cancers, now we're seeing 50% overall response rate as the bar to be competitive. We expect to exceed that with our data.
We've covered, obviously, the two that are expected to be in the clinic this year. You also have SEZ6. Can you talk about that as a target and what excites you there?
Yeah. 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 50%, 60% range, but with some significant toxicities on the hem tox side and still a high rate of ILD. 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 one trial, but with a linker payload system that generates a lot of toxicity. We really think we can build upon that, both because we're taking an interesting approach to targeting. We're using a biparatopic antibody that allows us to bind multiple sites 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. We have our highly stable linker payload system, which should generate a better safety profile overall. We really think we can be best in class relative to AbbVie in the SEZ6 space. Right now, my view is that AbbVie is kind of leading the pack of the SCLC ADCs out there, including DLL3s, as well as the B7H3 class.
Got it. Given that it's expected to enter the clinic next year, do you expect readouts sometime in 2026 as well? What is the?
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. Hopefully, we'll also have that data early in 2027, certainly by mid-2027.
All right. To close out, I guess, could you help us with your broad overall pipeline? Focus on the most important aspects of Whitehawk Therapeutics that you'd 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.
Certainly, we want to deliver on the milestones of IND filings and starting up our clinical trials. 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've played that pretty close to the vest so far, just given how competitive the space is. You'll see some of that data within, of course, 2026. 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. We really have an opportunity for three shots on goal across multiple different indications in the course of the next 12 to 15 months.
Yeah, great. I mean, it's super exciting. That's all the questions I had. Should we take any questions from the field?
It's a small group, so we understand if you don't.
Thanks. No worries. That's all the questions we have. I'd like to thank everyone for joining us today and look forward to our future discussion.
Thanks, Frank.
Thanks, Dave.