Hello, everyone. Welcome to the Jefferies Global Healthcare Conference. It's a pleasure to be here with Dave from Whitehawk Therapeutics. Hi, Dave. Could you introduce yourself and your company? Yeah, for sure. Hi, everyone. Dave Lennon. I am the Chief Executive Officer of Whitehawk Therapeutics. We're an ADC-focused company currently developing three ADCs with two that have entered the clinic earlier this year. We recently announced a financing of $87.5 million that extends our runway into 2028 as we pursue each of those programs through dose escalation findings in phase I. We have our third program going into the clinic in Q3 this year, and we look forward to provide data updates in the first half of 2027. Awesome. Thank you, Dave. You have an exciting pipeline, three ADCs, two that are going to have data in the first half of 2027. Now when we think about those two, the HWK-007 and the MUC16, we get questions and we're curious about what do you think, say the day after the data, what would get you excited about what kind of signals you'd like to see from here? What matters most to investors? Right. We had two programs. HWK-007 is a PTK7-directed ADC, and HWK-016, which is a MUC16-directed ADC. Each of these ADCs is based on the same linker payload technology, which is based on a linker payload called CPT113 and a bioconjugation process called Carbon Bridge Cysteine Re-pairing. It's quite a unique platform for an ADC. It provides ultra-high stability for each of our ADCs, which we think will translate into greater potency and importantly, greater tolerability due to both the stability I mentioned, as well as the nature of our TOP1 inhibitor payload. For each of the programs, there's different indications that we're pursuing. In HWK-007, we're pursuing non-small cell ovarian cancer and endometrial cancer. It's actually a focused phase I dose escalation program that really targets our ability to show differentiation versus other ADCs that are competitive in this field in those indications. When we think about data that gets us excited or our hypothesis is that we can achieve the high levels of efficacy, particularly on ORR rates initially in dose escalation that ADCs have been achieving to date, while improving the overall tolerability of our ADCs, and we would plan to demonstrate with that within the dose escalation. We've enrolled already a two-milligram cohort, which is a relatively high starting dose for HWK-007 and are enrolling a four-milligram cohort today. Ultimately, we see an efficacy bar in lung cancer of about 40% ORR and 50% ORR in gynecological cancers as an efficacy bar, and we anticipate tolerability, particularly heme-sparing effects of our payload to come through with relatively low Grade 3 based AE events with this program. That's what I think gets investors excited around this core program. MUC16 is similar in its construct and what we're trying to achieve, and that program focuses on ovarian cancer and endometrial cancer with the same expectations for benchmarks of what we potentially can achieve. Thank you for that overview. You mentioned again a little bit on the differentiating safety profile. I was wondering if you'd walk us through a little bit more how you have preclinical data? de-risking, indicating that you've built around stability, this low free payload, and the tolerability you've shown in NHP studies. Again, what should we think about in terms of when we start your dose escalating and what would be a dose limitation or something signal to watch for? Sure. As you mentioned, we had preclinical data at AACR this year where we showed HNSTD for all three of our ADCs off of this platform that achieved 60 mg/kg, which is relatively high in the ADC field. That gives us confidence about the potential therapeutic index that we can achieve with this and the relative tolerability that we're seeing, not only for that absolute number, but the types of events which were relatively minor that we saw within our cyno tox studies. Importantly, there is a parallel program that's being developed by our partner in China where one of the folks who originated the CPT113 linker payload. They reported some data on a CD56-directed ADC at ASCO this week. We can see in about 100 patients' worth of safety data there, the hematological heme-sparing effects that I talked about before, where they had zero Grade 3 neutropenia, very low rates of thrombocytopenia, and about 18% Grade 3 anemia, which is considered really low for the context of a Top1-based inhibitor, and that's while showing very promising efficacy signal in small cell and non-small cell patients in that trial. That was all China data. It's not our programs directly. There are some small modifications that we made in development of our ADCs, which moved from their program, which is a DAR4 to a DAR6. There's some variability in the translation potential of that data. We think it provides some good clinical support along with our NHP data for a really clean tolerability profile, relatively speaking, for an ADC. What we'll be looking out for, of course, as we dose escalate, is those stochastic events that occur that can be due to injury within patients on different dimensions. I think in general, though, what you're seeing with ADCs these days, it's less about actual DLTs that get developed and more about the overall tolerability profile relative to the risk-benefit that you're seeing in efficacy. We don't expect anything particular to hold us back as we dose escalate, but we will be testing how much efficacy gain do we get at each dose relative to the cumulative toxicity that we generate. Thank you, Dave. When we talk about ASCO, again, saw updates across the space, just regarding this asset, Hangzhou's DAC, again, similar, if you could just talk to us a little bit about that linker payload. Yeah. On top of that, you have some additional differentiation with, I believe, your conjugation, if you could just walk us through that. As I mentioned, we think we have a unique linker payload system that was developed by Hangzhou DAC, which is a Chinese-based company. If I step back for a second, the vast majority of ADCs today are made with what we call single-chain maleimide-based bioconjugation. It's maleimide cysteine-based bioconjugation, I should say. What happens in that process is that the disulfide bonds that exist between heavy and light chains of an antibody, and there are four of those within an antibody, are reduced to free up cysteines, whereby we then add the chemical linker payload structure onto those antibodies to produce ADCs. That can happen at four sites of disulfides or eight cysteines overall, and that's how you typically generate single-chain DAR8-based ADCs. The big difference for Hangzhou and our approach is that we actually use a paired linker system, whereby linkers are actually conjugated together and then added onto the antibody as a pair. It's quite a unique bioconjugation approach, or unique structure overall, and a unique bioconjugation approach. What it does is actually reestablish the disulfide bonds, or reestablish or replace the disulfide bonds that were typically there for the antibody and imparts a greater stability to the ADC overall, something that can't be replicated by single-chain-based bioconjugation with almost every other competitor uses. It's quite a unique platform and a unique chemistry that Hangzhou built. We improved upon that by moving from a DAR4 to a DAR6. That improves the overall potency of each ADC while maintaining tolerability in HNSTD, as I mentioned before. That, in addition to a couple other confidential steps in which we take technical know-how to improve stability of the ADC overall, gives us a version two of this platform for ADCs. We really look at that DXC006 data that I mentioned earlier from Hangzhou as the floor of what we may be able to achieve with this asset. That update at ASCO had overall response rates for that target, which were going into small cell and non-small cell, in the high 50s and high 40s ORR respectively for each of those indications, showing that the program and the platform is already very competitive in those spaces. Those are very stellar results given the tolerability that we're seeing with that platform. Thank you. Regarding PTK7, we do have some precedent for other ADCs in this space. How do you think about your asset and how differentiating it is? The great thing about PTK7 is that it's actually one of the most broadly expressed tumor targets that's really yet to be exploited in the ADC field. Yeah. It's present in up to about 70% of tumors. This is a really interesting target to go after. There was a Pfizer and AbbVie co-development program called Cofetuzumab pelidotin that looked to target PTK7 with a first-generation ADC based with an MMAE payload. That program actually was tested in non-small cell cancer, ovarian cancer, and triple-negative breast cancer, where it showed some initial efficacy signal anywhere from 20%-40% ORR in a small group of patients across those indications. Ultimately, the program was discontinued, probably because of the confluence of tolerability that was challenging with that MMAE-based payload, a lot of class toxicity associated with that, and the fact that it existed in a co-development between two large pharmas, which were headed in different directions at that time with their ADC commitments. That program was discontinued, but it provides the foundation of efficacy of the relatively limited potential on-target tox that could exist with PTK7 and really opened up the opportunity for people to go after this target. Now there are a couple of competitors that also now have switched over to the Top1-based ADC platforms, along with us going after PTK7. Lilly, Qilu Pharmaceutical, and Day One Biopharmaceuticals to name a few. Yeah. Thank you. We have your HWK-007 trial in a few indications, non-small cell, ovarian, endometrial. We did see, again, some other assets in that space as well. Feels like it's almost getting crowded. How do you think about the signals in that space? How do you rank the importance by indication of some of those tumors? If you could just share a little bit more, because again, the Top1 space, we saw 200 different assets there. If there's something that we should think about how HWK-007 improves that therapeutic index, potentially the linker stability, the Fc- Yeah Things like that. Thank you. Sure. The space is. I don't think it's almost getting crowded. It's definitely getting crowded. There's a lot of competition within our target, also within indications across different targets. We tend to think about really a couple generations of what's happened. I mentioned first-generation programs with MMAE payloads. A lot of people have switched over to the Top1 field. Generally, you're seeing that there's significant gains in efficacy, improved tolerability when you switch over to Top1s. Not all Top1s are created the same. I think what we really spend a lot of time doing is optimizing each technical parameter to get the highest performance out of our ADCs. The first thing is the antibody itself. We use high-affinity antibodies against PTK7. It's a really strong internalizing antibody that can target PTK7 and outperforms on an antibody level, Cofetuzumab, pelidotin, and Pfizer. We benchmark that performance versus the prior generation product and improved upon that with our antibody design. In addition, we attenuate the Fc region of the antibody itself. Attenuation of Fc limits the uptake of the antibody and ultimately the ADC by Fc receptor-mediated endocytosis, which can occur in inflammatory cells and is actually in the topo field, thought to contribute to high rates of ILD that we've seen with topos. Abrogation of that binding of specific uptake by immune cells by limiting the Fc receptor, allows us hopefully to minimize the ILD impact that topos can have. I went through the conjugation chemistry and the linker stability elements that are now optimized. We actually generate the best-in-class stability within the field. We cannot find a program which produces better stability for us, and that allows us to really limit free payload release into the circulation and limit the payload-related toxicity, mainly in the hematological compartment. We also use PEG-based masking, which helps hydrophobicity of the antibody and hydrophilicity of the antibody, I should say, and avoiding the hydrophobicity of the payload and improve circulation in PK, which allows us to achieve very long half-life of our product. Very long half-life in an ADC is important because topoisomerase damage actually needs time to accumulate within cells to drive cell killing, as opposed to being directly cytotoxic. We've optimized that PK component to get really long exposure of ADC, and that's achievable because of the high stability and limited free payload release. If you have a high unstable linker payload, you need to go to shorter half-lives because you don't want to generate that exposure to the bone marrow, and you need that period of recovery. Finally, we use a proprietary cleavage and a payload system. It's a triple alanine-based cleavage system that results in a proprietary exatecan analog being released into the circulation, or sorry, into the tumor, I should say, not into the circulation, at the site of tumor. That payload is actually designed to be less heme toxic because it doesn't cross the cell membrane as easily and really stays retained within the tumors itself. allowing it to focus its effect at that point. When you go through the entire technology stack that accumulates as you build an ADC, we've optimized every component to really drive for potency, which we've seen within our animal models. We're active around one mg/kg in animal models, and we know that translates directly into about a human minimally effective dose. We have one mg/kg as our minimally effective dose in human. We already started our trials and are starting to clear doses at two and four mg/kg, which we think will be active for efficacy, so we're not spending a lot of time through dose escalation within the trial. We have that great HNSTD we're working with, high bar. We could potentially dose up to 8 milligrams per kg, 10 milligrams per kg, or 12 milligrams per kg in humans to generate a very large therapeutic index to explore and determine where our best dose will be. Dave, thank you. That was such a thoughtful walkthrough of some of the differentiating aspects of your pipeline. I'm just curious, through this learning process, and you have some other early pipeline that have Top1 plus ADCs assets, how do you see some of the learnings that you've gone through and the differentiating aspects of your assets reading through to other parts of the pipeline? Yeah, it's a great point. Obviously, we'll learn a lot about dose from our first program, and that can translate directly into the next two programs that we have. As part of our recent financing, we actually signed an extension deal with Hangzhou DAC for up to five additional ADCs that we can put into our pipeline. We're really thinking very thoughtfully about how we bring those programs forward. These will not be your traditional single target, single payload-based ADCs. We're looking consciously about which indications really have still opportunity, where it's not yet as competitive, or where we think there's unique solutions that ADCs can bring to particular indications in the field, and how do we do that by selecting the right target or the right targets in combination and by specific formats to improve upon the selectivity against the tumor relative to healthy tissue and side effects, as well as thinking about payload combinations. The Top1 CPT113 linker payload will be the backbone, which we utilize within any of our new ADCs, but we're also looking at how we combine that with orthogonal cytotoxic agents or other novel payloads to create the next generation of ADCs, which we think will be potentially even more impactful, and also overcome what will be a growing problem of resistance to the Top1-based ADCs that you mentioned. Yeah. Thank you. Going back to the PTK7 asset, again, you mentioned a little bit about what we might be able to see. Just going back there, and in those indications, is there any thoughts on what would signal going into a particular one of those indications from that early data? Yeah. You mentioned how crowded it is- Yeah We look at each indication independently. Yeah across the entirety of what is there. When we focused on non-small cell, we actually picked a subset of that, which is EGFR wild type adenocarcinoma. The reason we did that is twofold. I think one is we wanted as homogeneous a population as possible, so as we accumulated patients, there was real clarity about what we were achieving within a population. Secondly, that we thought that's where the main opportunity lies within the non-small cell space, where ADCs up until this point have really topped out around 30% ORR, typically in these types of patients, and where we already saw 20%-30% with Cofe-P. Now, if we can build upon that, generally in these transitions from MMAE to Top1, you gain anywhere from 15 points-30 points of ORR. That puts us in that 35%-50% range, which we think could be really impactful for patients. We know that's what KOLs are looking for in terms of achieving differentiation on efficacy in the small cell EGFR wild type population. That's our bar and what we expect to hold ourselves to as we accumulate patients in dose escalation and backfill cohorts that we are utilizing early in our program to generate that bolus of patients. Along with that, we are actually requiring tissue in our non-small cell lung cancer patients and screening those for PTK7 expression, so that we can retroactively look and stratify potentially results by PTK7 expression. Importantly here, if we want to achieve some of these high ORR rates, it may be a requirement that we actually have selected patients down the road. Of course, we'll let the data drive whether or not that's actually the case. Yeah. Thank you. ASCO, we saw a couple of these MUC targets as well. Could you just, again, just introduce us a little bit more to the MUC16 for those that are new to the story and how we see that in endometrial and ovarian cancer, compared to some other targets, FOLR1, and some of the B7 stuff? Yeah. Right. The ovarian and endometrial cancer group is a smaller set of patient numbers than what you see with non-small cell. It's also a more homogeneous population across each of those indications, although there is stratification of different resistance mechanisms and mutation patterns within each of those patients. With all of that said, there are also a lot of targets which can be very specifically addressed within the ovarian space, which are upregulated uniquely within gynecological cancers, like you mentioned, FRα and others. MUC16, we think, is probably the best target to go after for ovarian cancer and endometrial cancer because it is so highly expressed. We know this because MUC16 is actually cleaved into the circulating biomarker called CA125. CA125 is the most common blood-based biomarker utilized by gynecological oncologists to monitor progression and response to therapy for endometrial and ovarian cancer. MUC16 is the originating molecule for that, and it actually gets cleaved at the surface of the cell and releases CA125 into the blood. It does so at such high levels that it's often used as a measure of disease progression, as I mentioned. The challenge has always been with targeting MUC16, is that circulating CA125 creates a huge antigen sink in the circulation for patients. If you target MUC16, particularly epitopes in that CA125 region, you have to dose really high to overcome the circulating epitope that exists within the blood to actually get your ADC or monoclonal antibody or TCE to the site of the tumor. Recently, we've been taking a strategy along with a couple others to actually target only epitopes that are not part of that cleaved portion, so they are actually below the cleavage site in the juxtamembrane region of the molecule, and they bypass that circulating CA125 antigen. Well, why go through all this work if this antigen is such a difficult one? Well, it's because it's so highly expressed. MUC16 is often three to 10 times more highly expressed than common markers, like you mentioned, FRα, CDH6, B7H4, NaPi2b, some of the things that have gotten a lot of attention recently. We think as a starting point, MUC16 is probably the best target we can go after. We've developed a clever way to get around the circulating CA125 issue that has plagued this, and then we bring along all of the benefits I mentioned with HWK-007 for our linker payload system, high potency, high stability, and high tolerability. Yeah. Thank you. We have another story that we want to share on the SEZ6, and you are going to clinical entry next quarter. You recently shared at ASCO some of the real-world characterization of this particular target, and I was wondering if you could just walk through some of that and why this is a relevant target? Yeah to look at. Yeah. The SEZ6, seizure protein six, is a protein that's expressed in certain neuronal cells and massively upregulated in neuroendocrine tumors like small cell lung cancer and other neuroendocrine neoplasias. SEZ6, you may get the story now, we spend a lot of time thinking about what's the best target for a particular indication, and with SEZ6, it's really the highest expressed target in this somewhat smaller category of neuroendocrine tumors. The prototypic one so far has been DLL3, and SEZ6 is expressed at least as high as DLL3, if not higher, and therefore forms a foundation of a great target to go after for this class of molecules and can potentially be combined with DLL3 therapies. We did some work to show that across subsets of small cell lung cancer, across progression of lung cancer, so SEZ6 is very stably expressed regardless of stage of disease and metastatic potential. We think really establishes SEZ6 as a great target to go after. It is validated because of the program ahead of us from AbbVie, which forms the foundation then of this being a highly expressed and clinically validated target to go after with an ADC. Yeah, thank you. We saw some data also at ASCO in endocrine and then, sorry, neuroendocrine small cell lung cancer. from the 706 asset. Any thoughts on how we should interpret any read-throughs from that to your asset? Yeah. ABBV-706 is the SEZ6-targeting ADC that they've developed, showing some really promising efficacy signal, greater than 50% ORR in small cell lung cancer. I think what's interesting with that program, AbbVie has built a platform on a payload called the exatecan. Exatecan is a super potent payload, so it really does very well in driving efficacy of ADCs. The challenge is it also comes along with a lot of toxicity, particularly heme toxicity. As an example, in their expansion dose within small cell, they generated 40% Grade 3 anemia in that program, which is really difficult for patients to deal with overall. Very potent molecule, validates the target, but we would think really a lot of opportunities to improve tolerability for patients with that. By improving tolerability, we can actually increase dose intensity, which should allow us to achieve even greater efficacy than the AbbVie program. We use a very unique antibody here. We use a biparatopic antibody against this target, and we know this antibody is actually about 2x-3x more potent in terms of internalization and cell killing than the AbbVie antibody. Again, we've taken every step to design a molecule that really can be best in class against the SEZ6 target. Thank you. As we prepare for the clinical entry of this, could you walk us through some of the design and how you've thought about the best way to show some early signal here, and what we expect to see? Yeah. Yeah. This program will go in the clinic in Q3 of this year. I just want to reiterate, that's three clinical shots on goal over the next 12 months to look out for, and really an opportunity for us to hit on any one of those being a major value inflection, if not all three. The SEZ6 program will target small cell lung cancer initially, and we expect to see data in the second half of next year from that program in dose escalation. We will limit that program initially to small cell lung cancer, and then look for expansion in neuroendocrine tumors and other places as we go forward. Again, with the demonstration that we really have a best-in-class asset driving that decision to bring the program and expand the program further. Thank you. As we continue to get more data, and congrats on the three shots. I remember last year in November we were talking, and we're here, and it's been great to see the execution there. Regarding just the PK and biomarker readouts, the way that we should think about the PK package for some of your platform, what are maybe some things we should expect to see regarding just some of the PK metrics, like your ADC, your total antibody, things like that. Yeah Exposure response? Yeah. Yeah. We'll really be looking at the half-life that we see and replicating half-life initially of this. We saw a very long half-life within monkey studies. We'll be looking for that in our human studies in PK. From a stability profile, we always look at what is that free payload that's being released, and we benchmark that stability in our human PK data overall. Ultimately, what we expect to see is half-lives that extend beyond a week to 10 days for each of our programs, and that stability profile that keeps free payload release under the therapeutic limit of our payload, which is a couple nanograms per mil. Thank you. One more question on, you have optionality for five additional CPT113 ADC programs. How do you think about that optionality, and then how do you think about partnering also, if I can ask a combined question there? Sure. Sure. That's two ends of the spectrum in terms of how we bring new assets in and how we might develop assets going forward. In terms of bringing new assets in, we're really selective about what we want to bring in. We're not trying to fill the pipeline to fill the pipeline. We're really looking for unique value-creating opportunities that add to what we're doing versus our three assets that we already have, which is already a good foundation to build on from a value perspective. You'll see us make very deliberate decisions about new programs that we initiate. Our expectation is those programs would come in the second half of 2027. Also would come after data release on our first two programs and would be also somewhat momentum-driven at that point in time based on our learnings from those programs. In terms of partnering, I think right now what we're focused on is execution of our programs, and getting to those clinical inflection points. Yes. We'll tackle partnering after we have data. Got it. Thank you, Dave. That was fantastic. Thank you everyone for joining us. Thanks, Shepard. Thanks.