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

All right. My name is Frank Tang, and I'm with the investment banking division of 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 White Hawk story, could you give us an overview of where the company sits today as a next-generation ADC platform, your pipelines and your priority?

Yes, 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. So as you noted, yes, we repositioned the company in early 2025. What's formerly known as Adi Bioscience. And we are now an ADC company focused on developing next-generation ADCs against kind of existing tumor biology. Paramount to that transition was the in-licensing of 3 ADC portfolio from WuXi Biologics. And so our first program is called Hawk007 and that is targeting PTK7. The second program is HAWK016, which targets MUC16. And the third program is HAWK206 which targets SEZ6. The first 2 programs, so '07 and '016, entered the clinic in the first quarter of this year, and they are progressing through Phase I dose escalation. And then the third program, HAWK206, will be entering the clinic this quarter. And kind of from a near-term priorities perspective, obviously, the #1 focus is continuing to execute the programs in the clinic. We will be sharing data on the first 2 programs, 007 and 016 in the first half of 2027. And then lastly, we've done some selective expansion to our pipeline over the beginning of the year. And so that's where our priorities are focused.

Yes. Great. As you mentioned, your 3 lead ADCs are in-licensed on WuXi built on your CPT 113 linker payload plus your proprietary plus your proprietary CBCR bioconjugation. What makes the platform -- there's some feedback. Okay. What makes the platform differentiated versus first-generation ADC?

Yes, I can take that one. So essentially, there's a couple of things about the ADCs that are important in the platform. The first is like the actual bioconjugation itself. So the first on ADCs were always, I'd say, restricted by deconjugation events or a retro Michaels reaction that typically called in the field, where our technology differs in a couple of places. But the first is on the conjugation to cystine. We use hydrolysis steps to stabilize that linkage but the carbon bonds or the carbon bridge that we call it system repairing, essentially, it's replacing the dicesulpide bond that used to exist in the antibody now for carbon bond and it gives it a much stronger biophysical properties than anybody, and that translates into stability for the antibody as well as the ADC itself. And then on the linker payload system itself, right, what makes it different is we use some hydrophilicity place using peg masking as well as we have our own unique triple alanine cleavage site for which is only processed by lysosomal enzymes. So only when it's some tarnishes the payload get released and then releases are on proprietary CPT 116, which is our own top 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 HNSTD and cynos. And more importantly, we have like very high, we'll say, submit efficacy in preclinical model. So really just from Bueno Beken, we have much greater potency and much higher safety.

Excellent. Yes. So I mean moving into the -- focusing on the clinical pipeline Scott, as you said, Hawk007 and Hawk016 or both enrolling Phase I dose escalation with the initial data expected still in the first half of '27. Could you give us an overview of both programs why the PTK7 and MUC-16 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 of these trials?

Sure. So 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're looking toward are non-small cell lung cancer and specifically EGFR wild type on squamous -- there's less competition there. That's 1 of the reasons we're looking there. And then also platinum-resistant ovarian cancer and endometrial cancer. And with PTK7, there has been some previous validation of this program or for the target, it was a program called cofituzumab peladotin, which was a Pfizer AbbVie program, which showed some promising efficacy but had class lending toxicities as AE like payload. And so what we're hoping is that with our differentiated antibody and liquor play platform, to be able to deliver improved results over those early ADCs. The second program, MUC16, our 016 targets M16. Again, that's highly expressed in gynecological cancers. And that program also has some previous validation is from the DMUC programs from Genentech. Again, those programs showed some promising efficacy, but were hampered by toxicity. And the main issue that you had there was the molecule binding to circulating CA125, 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 MUC16 or the nonshed 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've said that we'd like to have 20 to 30 patients per program. So for 007 and 016. And from a bar perspective, for non-small cell lung, we're thinking 35% to 40%. It's kind of our internal benchmark. And for the gynecological indications, we're looking at 50% -- and then in both cases, a tolerable or a manageable safety profile.

It's great to hear. Moving on to HWK-206 in small cell lung cancer and neuroendocrine tumors, that's on track to start Phase I this quarter and your ASCO analysis positioned SV6 as a highly expressed target or correlated with -- how would that -- how does that derisk the program and open up combination potential?

Yes. I think it's the former more than the later with respect to like derisking, I think it's the best derisker, honestly, is the AbbVie molecule AbV706. That's let's call it like a monoclonal single epitope binding ADC in contrast or biparatopic. We've compared that, of course, to our own molecules and had posters at AACR, highlighting the bypower topic has much greater internalization, especially when the target is lower and resulting in greater cell killing and efficacy. So I think really that analysis at ASCO, I mean it really just helped given DLL 3 years of validated target on its own for a TCE as well as ADCs I think it really just does give that opportunity as you're alluding to the potential combinations down the line, whether that's with TCEs or whether that's with another ADC or other DLL-3 target agents, it just really just backs up the concept to highly expressed targets on small cell have potential combination impact.

That's good to hear, given that, that would be the next asset in clinic. Maybe digging a bit more around the platform and your strategy with you guys having done this collaboration with WuXi. Now that you've expanded the platform with HANGZHOUHunza, the options for CPC 113 across 5 additional programs and biocylogen collaboration for bispecifics and bispecific ADCs, and we know you have ambitions to find more INDs and push more assets into the clinic in the next 12 to 24 months. What makes you excited about the expansion? How do you balance it around kind of what your existing have in the 3 assets versus what else you can expand into?

Yes. Maybe I'll start and then turn it over to David for some comments. I think the first thing I would mention is our main priority is the advancement of the first 3 programs through clinical development. And so there's not really any, I would say, investment trade-offs or anything like that related to these new collaborations. These are option agreements that I think make a lot of sense for us the Hangzhou DAC collaboration, in particular, right, it's 4, 5 more -- potential for 5 more ADCs using the CPT 113 linker payload platform. And that made a lot of sense for us based on what we've seen from our preclinical data, but also from the data that Hangzhou DAC shared for their own program, DXC006 at ASCO last year. That's their CD56 targeted program. And so I think based on that, we like what we see there in sort of kind of doubling down, if you will, on that platform. And then for biocytogen, I think just kind of thinking about how we move forward and I'll let David talk about that more in a second. And then the last comment I would make is from an investment perspective, these are option agreements. So essentially, low -- the investment is pretty low until we would get the IND readiness. So David, do you want to talk about excitement around the programs?

Yes. I think really like with these license deals, it really just gives us the opportunity to stay at the leading edge of an ADC company. The base agent agreement, I mean, it gives us access to bispecific antibodies that are choosing and allows us to target the white space, if you will, where there's still opportunities for basically antibody drug conjugates to have an impact. As Scott said, the license agreement extension, if you will, with HANGZHOU DAC, really -- we see our platform is like the basis of our company, but -- we also are well aware and are exploring other combinations for multiple payloads to be loaded on to ADCs. So really is the goal, again, is about generating, obviously, the next next gen, if you will, of ADCs, but more importantly, addressing populations of patients where still the current ADCs that we see are not addressing. And so that's why we're basically reselling to do our own pipeline.