Whitehawk Therapeutics, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

All right. My name is Frank Tang, and I'm with the investment banking division at Morgan Stanley. Thank you all for joining us today for the fireside chat with Whitehawk Therapeutics. I am joined today by CFO Scott Giacobello and Chief Scientific Officer David Dornan. Welcome, and thank you for joining us today. Whitehawk is a substantially transformed company since the new shift and focus on ADCs. For investors new to the Whitehawk story, could you give us an overview of where the company sits today as a next-generation ADC platform, your pipelines, and your priorities?

Yeah, sure. First of all, Frank, thanks for having us here. We're happy to be here at the Morgan Stanley conference and to tell everybody a little bit more about Whitehawk Therapeutics. As you noted, yeah, we repositioned the company in early 2025. It was formerly known as Aadi Bioscience, and we are now an ADC company focused on developing next-generation ADCs against existing tumor biology. Paramount to that transition was the in-licensing of a three ADC portfolio from WuXi Biologics, and so our first program is called HWK-007, and that is targeting PTK7. The second program is HWK-016, which targets MUC16, and the third program is HWK-206, which targets SEZ6. The first two programs, so 007 and 016, entered the clinic in the first quarter of this year, and they're progressing through phase I dose escalation.

The third program, HWK-206, will be entering the clinic this quarter. From a near-term priorities perspective, obviously, the number one focus is continuing to execute the programs in the clinic. We will be sharing data on the first two programs, 007 and 016, in the first half of 2027. Lastly, we've done some selected expansion to our pipeline over the beginning of the year, and so that's where our priorities are focused.

Yeah. Great. As you mentioned, your three lead ADCs are in-licensed from WuXi, built on your CPT113 linker payload, plus your proprietary CBCR bioconjugation. What makes the platform-- There's some feedback?

Yeah. Okay. What makes the platform differentiated versus first-generation ADCs?

Yeah, I can take that one. Essentially, a couple of things about the ADCs that are important on the platform. The first is the actual bioconjugation itself. First-gen ADCs were always, I'd say, restricted by deconjugation events or a retro-Michael reaction, they're typically called in the field, where our technology differs in a couple of places. But the first is on the conjugation to cysteine. We use hydrolysis steps to stabilize that linkage, but the carbon bonds or the carbon bridge, that we call it, cysteine repairing, essentially, is replacing the disulfide bond that used to exist in the antibody now with a carbon bond, and it gives it much stronger biophysical properties than antibody, and that translates into stability for the antibody as well as the ADC itself.

And then in the linker payload system itself, what makes it different is we use some hydrophilicity plays using PEG masking. As well as we have our own unique triple alanine cleavage site, which is only processed by lysosomal enzymes, so only when it's internalized does the payload get released, and then it releases our own proprietary CPT113, which is our own topo-1 inhibitor, and really that's designed to minimize toxicity in the bone marrow by reducing forward permeability. So eventually, inhibiting, for the most part, uptake by those, essentially heme compartment. And we've shown this from many different ways in preclinical models. The ultimate results in a much more stable construct, highest HNSCC in cynos, and more importantly, we have very high, we'll say, sub mg per kg efficacy in preclinical models. So really just from bookend to bookend, we have much greater potency and much higher safety.

Excellent. So, moving into the focusing in on the clinical pipeline. Scott, as you said, HWK-007 and HWK-016 are both enrolling phase I dose escalation with your initial data expected due in the first half of 2027. Could you give us an overview of both programs, why the PTK7 and MUC16 are the exciting targets and the indications? And maybe you can guide us a little bit on what you think would be considered a compelling early signal out of each trial.

Sure. HWK-007, as I mentioned, targets PTK7, which is the most broadly expressed tumor target yet to be developed, and I think third overall from an expression perspective in cancer. The indications that we are looking toward are non-small cell lung cancer and specifically EGFR wild type on squamous. There is less competition there, that is one of the reasons we are looking there. Also platinum-resistant ovarian cancer and endometrial cancer. With PTK7, there has been some previous validation for this program, or for the target. It was a program called Cofetuzumab pelidotin, which was a Pfizer/AbbVie program, which showed some promising efficacy but had class-limiting toxicities as its MMAE-like payload.

What we are hoping is that with our differentiated antibody and linker payload platform, to be able to deliver improved results over those early ADCs. The second program, MUC16, or 016 targets MUC16, again, that is highly expressed in gynecological cancers. That program also has some previous validation. It is from the DMUC programs from Genentech. Again, those programs showed some promising efficacy, but were hampered by toxicity, and the main issue they had there was the molecule binding to circulating CA 125, which limited the ability to get enough drug to the tumor, and also resulted in increased toxicity. Our program is a little different in that we target the membrane-bound portion of MUC16 or the non-shed portion, which we believe bypasses the circulating 125 issue, and hopefully will lead to more promising efficacy and safety in that program.

As far as data, in the first half of 2027, we have said that we would like to have 20 to 30 patients per program, so for 007 and 016. From a bar perspective for non-small cell lung, we are thinking 35%-40%. It is kind of our internal benchmark. For the gynecological indications, you are looking at 50%. Then in both cases, a tolerable or manageable safety profile.

That is great to hear. Moving on to HWK-206 in small cell lung cancer and neuroendocrine tumors. That is on track to start phase I this quarter, and your ASCO analysis positioned SEZ6 as a highly expressed targeted correlated with DLL3. How does that de-risk the program and open up combination potential?

Yeah, I think it is the former more than the latter. With respect to de-risking, I think it is the best de-risker, honestly, is the AbbVie molecule, ABBV-706. That is what we will call a monoclonal single epitope binding ADC, in contrast or biparatopic. We have compared that, of course, to our own molecules and had posters at AACR highlighting the biparatopic has much greater internalization, especially when the target is lower, and resulting in greater cell killing and efficacy. I think really that analysis at ASCO, it really just helped, given DLL3 is a validated target on its own, for a TCE as well as ADCs. I think it really just does give that opportunity, as you are alluding to, the potential combinations down the line, whether that is with TCEs or whether that is with another ADC or other DLL3 target agents.

It just really backs up the concept that two highly expressed targets in small cell have potential combination impact.