Right. Right. Welcome, everyone, to Jefferies 2025 Global Healthcare Conference. My name is Roger Song, one of the senior analysts covering MedTech Biotech in the U.S. It's my pleasure to have to introduce our next presenting company, Whitehawk Therapeutics, and then CEO Dave. And then it will be a presentation, and if we have some time to do a Q&A, we'll save that toward the end. Dave.
Thank you, Roger, for the introduction. It's always great to be here at the Jefferies Conference, and thank you for inviting us. I'm Dave Lennon. I'm the CEO of Whitehawk Therapeutics. I'm really proud of the team at Whitehawk, where we're combining breakthroughs in tumor targeting, leading ADC technologies, and a focused clinical strategy that's intended to efficiently deliver improved ADC therapies. I'm excited to talk to you more about that today. Slide two. Oh, do I advance it? Sorry. All right. Just as a reminder, the statements made on today's call will include forward-looking statements representing our views only as of today, June 4, 2025. I'd like to provide a brief reminder about our evolution from our prior company, Aadi Bioscience.
Back in December, we announced a series of strategic transactions, including the in-licensing of three ADCs from WuXi Biologics, the divestiture of FYARRO to Kaken Pharmaceuticals, and $100 million pipe financing. We have substantially closed the transaction with Kaken, at which time Aadi became a subsidiary of Kaken, and Kaken assumed ownership of the Aadi name, trademark, and the FYARRO business. In March, we then relaunched as Whitehawk Therapeutics, focused on rapidly progressing a multi-asset portfolio of advanced ADC therapeutics with the potential to make a meaningful difference in a large number of different cancer populations. Whitehawk is led by a seasoned management team with deep ADC experience and a track record that reflects successful operational execution, but also deal-making success. I'm proud of the top-tier investors who have supported our transition to Whitehawk, including Avoro Capital, Ally Bridge, OrbiMed, Suvretta, Acuta, QVT, and others.
Now, turning to the next slide, as Whitehawk, we've developed a framework that establishes a clear value proposition that's differentiated in the ADC field. Firstly, we're building on the foundation of established tumor biology. We were deliberate in identifying promising tumor targets that are both clinically validated through precedent programs and broadly overexpressed across a wide range of cancers. By leveraging clinical validation, we know we have druggable tumor targets, and because these targets are broadly overexpressed, we can apply them to high-potential cancer indications with significant patient populations. While first-generation ADCs have led to significant advances in cancer treatment, we know these ADC platforms are hindered by limitations of payload, targeting approaches, linker instability, PK, and toxicity profiles. These are all contributing to what we like to put together as a limited therapeutic window.
To overcome these challenges, we're applying an advanced ADC platform technology that is engineered for minimal off-target toxicity, greater stability, and a larger therapeutic index compared to first-generation predecessors. Importantly, we're hyper-focused on speed and efficiency to major data inflections since we believe the proof is in the clinical pudding. We are rapidly advancing our portfolio to clinic with INDs for all three candidates anticipated by mid-2026. After completion of the transaction-related payments recently, including payments for upfront licensing fees to WuXi for the ADCs we in-licensed, we expect to have cash and cash equivalents of approximately $185 million to prosecute our ADC portfolio. We anticipate this will fund operations into 2028 based on current plans, including anticipated key clinical data from our phase ones across the portfolio. Let's dive into the portfolio a little bit.
Our portfolio consists of three assets, which I like to say are focused on validated but not inundated tumor targets, meaning we have identified tumor targets where the target itself has been validated by a prior, mostly large pharma ADC programs, but were discontinued due to toxicity concerns of first-generation ADC platforms. All of the targets that we have here have the potential to be first; we have the potential to be first or second into the clinic with a next-generation version against these targets. We believe our targets, PTK7, MUC16, and SEZ6, are highly compelling for their tumor-specific expression and limited normal tissue distribution, offering the potential for selective tumor killing with reduced off-target toxicity. HWK-007 targets protein tyrosine kinase 7, or PTK7, which is an oncofetal pseudokinase that drives early embryonic development.
Subsequently, it is downregulated after birth and becomes activated by tumors and is highly overexpressed in a broad range of tumors as they arise. There are no approved PTK7 ADCs, but based on promising efficacy seen in clinical trials from Pfizer-AbbVie's ADC, cofetuzumab pelidotin, or COFI-P, it is becoming a very popular target for research. Our second target, HWK-016, is the only known ADC that targets the membrane-bound portion of MUC16, a glycoprotein with low-level expression in normal adult tissues, but often overexpressed and shed in tumors of female origin, including ovarian, cervical, and endometrial cancers. Shed MUC16 is actually better known as CA125, the common blood-based biomarker used by gynecologists everywhere for cancer screening and disease monitoring, especially in ovarian cancer. It makes MUC16 a very widely utilized and clinically validated target in gynecological cancers and was previously studied by Genentech, who had a MUC16 program against this target.
Finally, we have HWK-206, which is designed to address the neuronal target SEZ6. SEZ6 is a CNS-limited protein overexpressed in tumors of neuroendocrine origin, most prominent example of this being small cell lung cancer. This is an aggressive high-grade neuroendocrine carcinoma for which limited treatments exist today, and overall class competition is limited. AbbVie is demonstrating meaningful phase I responses for this target in small cell, as well as some recent data in neuroendocrine tumors at ASCO last week. We believe we have an approach that can build on and surpass the early data from that program. Underlying each of these programs is the advanced ADC technology platform developed by Hangzhou DAC, which is called CPT113. This ADC architecture is based on a novel topo-1 inhibitor payload and a highly stable linker chemistry.
Through detailed development of ADC technology over the last dozen years, Hangzhou DAC has invented a series of novel characteristics in this linker payload to impart leading stability, PK, payload delivery, and payload delivery that is the foundation of what we believe can be a best-in-class series of ADCs. Importantly, though not part of our portfolio, Hangzhou DAC has two internally developed programs that are utilizing the same platform, and these have reached successful INDs in China and are currently in dose-escalating phase one clinical trials. Let's get more details into our platform and how it translates into clinical benefit. As context, first-generation ADCs were challenged by high-free payload release in circulation, limiting their therapeutic window as high-free payload can generate significant off-target side effects and limit dose escalation. CPT113 is an advanced ADC platform that improves upon those limitations of first-generation platforms by engineering three critical components.
Payload, we use a proprietary topo inhibitor payload that minimizes off-target effects. Linker design, we have a highly stable, cleavable linker that supports low-free payload release in circulation and focuses target at the site of tumor. Then pharmacokinetics profile, and that's the ability to deliver high DAR with enhanced PK and half-life stability that enables optimal dosing for patients. The right-hand side of this slide generalizes that concept of therapeutic index improvement that we are expecting from the implementation of next-generation ADC platforms, increasing the potential for dose intensity for patients. As an example of how this is manifest in actual advances for patients, you can see here a series of examples that look at individual targets where first-generation platforms have subsequently been challenged by next-generation, more stable topo-based platforms.
In comparison to largely tubulin inhibitor-based platforms at the outset in the first generation, more stable topo-based platforms are generating efficacy gains in the 16-45 percentage point range with an average of more than 30 percentage points in overall response rate amongst patients. This also coincides with improvements in durability of response and overall more tolerability from a side effect profile. If we take this example of gains that we are seeing in the movement from first-generation to next-generation platforms, on slide eight, what we have done is then given the theoretical concept of what we think we might be able to do with our own internal programs like HWK-007. That was HWK-007's precedent molecule, which was a Pfizer program I mentioned earlier, cofetuzumab pelidotin, which provided proof of concept for PTK7 in ovarian cancer and non-small cell lung cancer, as shown here.
The range of responses is shown in the light green bars, and already those programs were performing at the relative level relative to standard of care with responses seen across a range of tumor types. Despite encouraging signals here, COFI-P was limited due to reduced dose intensity and a narrow therapeutic index driven by toxicities consistent with the class effect of first-generation MME-based payloads. What happens if we apply the advanced ADC platform that we're looking at, CPT, and some of the benchmarks that we saw before? It is a huge gain in efficacy potential. What these graphs represent is placement of the phase one COFI-P data and the addition of that switch to a new payload.
In switching to a new payload with HWK-007, we're extrapolating from prior examples that we may expect to generate efficacy gains on average of 15%-30% or more in objective response rate over cofetuzumab pelidotin, and this level of improvement would be disruptive well beyond ADC standard of care, surpassing much of the existing standard of care data and also potentially being highly competitive with promising early data from other next-generation platforms. This is just an example for HWK-007, but we expect similar improvements with our other two programs, which are also based on precedent molecules where we're switching over to an advanced topo-based platform. This is a more traditional view of the pipeline for all three assets. We're working towards filing each of these INDs rapidly with a plan to submit all three INDs by mid-2026, over the course of the next year.
We reiterate these assets are designed to target proteins that are broadly overexpressed in multiple tumor types with significant unmet needs. This slide highlights the cancer indications where these targets have established clinical data, but also shows the numerous expansion opportunities, showcasing the substantial market potential of our entire portfolio. Starting with HWK-007, this is really an opportunity to be among the first and next-wave ADCs for high PTK7-expressing cancers. PTK7 is one of the most broadly expressed tumor targets out there. It's estimated that up to 60-70% of patients will express PTK7 sometime during their cancer journey. Initially, our phase one trial is planned for non-small cell lung cancer and gynecological cancers like ovarian cancer, with the potential to expand into other novel indications. HWK-016, we plan to submit by around the end of this year and currently is in IND enabling studies.
The phase one trial is planned initially in ovarian cancer, leveraging the biomarker CA125, which is part of that story. Ultimately, we see expansion potential into other gynecological cancers, as well as pancreatic cancer and some non-small cell lung cancer targets. I mentioned HWK-206 already. That IND will be submitted in mid-2026, and then multiple opportunities to address neuroendocrine-based neoplasias, as well as potentially some CNS tumors. Just going a little more detail into, I'll just highlight a couple of things about each of the targets. As we mentioned, PTK7 is broadly overexpressed and upregulated across multiple tumor targets, and there are no approved assets against this target today. We've already covered some of the data that was generated by Pfizer in their first-generation program, and this is just a restatement of some of the efficacy results that we're seeing here.
Unfortunately, we did see significant toxicities that were associated with payload in this case, but it creates an encouraging platform for us to build upon. Ultimately, we believe that we've already generated a differentiated next-wave PTK7-directed ADC in HWK-007. We're showing here some in vivo data of the potency of this molecule relative to cofetuzumab pelidotin in a lung cancer cell model. Ultimately, we believe this has an opportunity to translate into significant gains against that precedent data that we saw previously. In HWK-016, we're talking about MUC16 overexpression, and as I mentioned, this is overexpressed in cancers of female origin, which you can see listed here. Now, there was significant precedent data with MUC16, as I mentioned, with Genentech, where they saw at a relatively high dose for an MMAE payload, overall very high rates of response amongst patients.
Interestingly, part of their hypothesis about why it took such a high dose to generate those responses, and they did not see any response in some of the lower doses, is the fact that MUC16 is actually cleaved and shed into the circulation, and their antibody targeted the shed portion of the molecule, thereby generating something called the antigen sink effect, which is shown here. In this model, what you see is the tumor actually cleaves MUC16 from its surface, and that is then transported into the circulation where it can be measured as a circulating biomarker CA125. That also leads to the potential, if the antibody or ADC is targeting that molecule, for it to be binding in circulation and thereby cleared before it reaches the tumor.
To overcome the antigen sink effect, we've targeted our molecule to the membrane-bound portion of MUC16, so the non-shed portion, thereby bypassing any circulating CA125. Preclinical data shown here demonstrates that HWK-016 has superior tumor inhibition in vivo compared to Genentech's DMUC program in a high-shedding model of ovarian cancer, the OVCAR3 cells. In this case, there's almost no effect from the DMUC program, but highly potent effect from HWK-016. From a clinical perspective, we plan to start our phase one trial in ovarian cancer with high CA125 expression in Q1 2026, with the potential to expand to additional cancers affecting women where we can have significant impact, for example, in endometrial and cervical cancer. Finally, just a reminder, our third asset in the portfolio is SEZ6, a CNS-limited protein, which is overexpressed in some of the tumors shown here.
Importantly, this molecule has a precedent in AbbVie 706, which is currently under development against this SEZ6 target, and showing some really promising results initially in small cell lung cancer at ASCO 2024, and then in neuroendocrine tumors recently at ASCO 2025. While this is important progress, we believe there are opportunities to apply novel ADC engineering to improve upon and generate even greater gains for these patients. The approach we're taking with SEZ6 is to utilize a Biparatopic molecule to target that protein with the antibody and then leveraging the CPT113 platform for our ADC construct. Biparatopic antibodies, which bind two different epitopes of the same protein, allow for transbinding to enhance receptor clustering and internalization, a key driver of ADC effectiveness. Biparatopic superiority in target specificity, binding, and internalization of ADCs, we believe, can translate into greater efficacy and safety gains for patients with different neuroendocrine tumors.
Our asset, HWK-206, is the only Biparatopic ADC in development for small cell lung cancer and shows the potential to outperform available treatment approaches. We've seen this play out already in preclinical models where a Biparatopic ADC is showing superior binding and internalization compared to single epitope SEZ6, including to the antibody that's utilized in AbbVie 706. We plan to explore the potential in our planned phase one trial of small cell lung cancer and neuroendocrine tumors where there is significant unmet need. Just to wrap up and leave a few minutes for questions, I want to just reiterate our portfolio contains three clinically validated, broadly overexpressed tumor targets, leveraging an advanced ADC linker payload architecture. It's multiple shots on goal that we can generate over a short period of time.
We scoured the ADC universe and selected targets with clinical efficacy from prior big pharma programs, but where the next wave of topo-1 inhibitor-based competition is limited. There is still room for us to excel against each of these targets and deliberately move beyond the limitations of first-generation ADCs. With multiple shots on goal, our assets represent a differentiated opportunity not just to participate, but to lead in each of its respective categories. We are moving quickly, targeting filing of our three INDs by mid-2026, including HWK-007 in Q4 of this year, HWK-016 by the end of 2025. Lastly, we are well capitalized with the cash expected to fund all of the efforts that we need to do to put these programs into the clinic and to deliver data early in 2027, well ahead of our cash out in early 2028.
I'll end my presentation here and say thank you and look for questions.
Thank you, Dave.
Thanks.
Yeah, I think maybe we can start with the platform because this is absolutely a very interesting next-gen ADC, given you have your China partner in doing two other pipelines using the same platform. How much do you know about those two compounds and then how and when are we going to see what? Are we going to see those data for investors to give a little bit more read before you have your own data?
Yeah, it's a great question. The assets are with a partner. It's a private Chinese company, and they will release the data when they think it's appropriate for their strategic interests. What I can say is they are a very good partner to us. We're very close to them. We do gain access to that information as appropriate. Everything we've seen is consistent with our expectations for how the product should perform in terms of stability, efficacy, and toxicity to date. I can't say when we'll see that data exactly, but I can say that we're confident that it'll demonstrate the potential of this platform.
Do we know the target or indication for those two compounds?
Yeah, so there's two targets. One's a TROP2-directed ADC, and the other one is a CD56 or NCAM-directed ADC, which is a small cell cancer target.
Got it. Okay, great. In terms of the development stage, it's in phase one in dose escalation. That's the...
Yeah, that's right.
Got it. Okay, great. Then moving on to your three exciting programs. I think the IND is upcoming. We just came from the ASCO. I do see the SEZ6, the AbbVie compound. They have some new data. Maybe any high-level comments for that program and then your TPP against this lead competitor, so...
Yeah, so it's great to see validation of this target, especially for neuroendocrine patients. There's not a lot of treatments out there, and certainly ADCs have not focused on neuroendocrine targets as a modality. Really impressive to see both the data in small cell lung cancer, which showed over 60% overall response rate initially in a large number of patients, and neuroendocrine tumors, which I think was 36%, I want to say, ORR in neuroendocrine tumors. Really impressive initial responses for all those patients. I would say when you look at the profile overall, there are some significant toxicities associated with that payload from AbbVie. AbbVie uses a number of platforms they utilize, but that platform is the same platform that's being utilized in the AbbVie 400 program, or I think it's called Temed A or something right now, Taliso A, the version.
In any case, what you see in that program is a significant heme toxicity profile, 40-50, sometimes higher, grade 3 toxicities at their intended doses for, sorry, grade 3 hematological toxicities at their intended doses with all supportive care in place. We think there's some opportunities to improve both with our Biparatopic approach in terms of improving the therapeutic intensity and ability to scale or increase the dose, but also with our platform, potentially a better safety profile that we could generate overall. What we're looking for in this construct is really what we hope is the best in target approach against that and ability to build upon the precedent that AbbVie is setting in the space.
Got it. I believe you did a lot of the diligence when you licensed those three programs. You already gave us a little bit of preclinical data as well. How much should we expect from you in terms of the IND-enabling data before you file the IND or along the IND filing?
Yeah, I think the ADCs are a hyper-competitive space these days. We raised money to get to the next milestone of clinical data readout. Release of preclinical data, I think, will be dependent upon when we think it's most appropriate. I would say it's unlikely that we would do that prior to filing the IND, mostly because we don't want to give information to our competitors about how we're going to differentiate and beat them.
Yeah, totally. Yeah, you do not need to give away the information unnecessarily, right? Okay. Yes, you already shift towards the company to the Whitehawk, the wholly owned ADC pipeline. But you also have the FYARRO as the legacy program. So maybe just remind us where you are for that and then completely shift towards the new direction.
Yeah. From a transition perspective, we completed the full transition in the last week of March of this year and then relaunched as Whitehawk at that time. With the completion of the transaction, FYARRO and the Aadi brand are completely now a subsidiary of Kaken. I would not comment more than what we said about that business since it is no longer ours, and it is really Kaken's information to move forward. They are a strong company and committed to bringing and continuing to have that product serve patients in the US, where it plays a really important role treating patients with PEComa.
Got it. And then just lastly, for the current cash runway, what's already included in the operational plan? It seems you are having quite an active kind of IND-enabling activity and then also moving to the clinical.
Yeah. As I mentioned, we have cash runway into early 2028. That anticipates our ability to complete our IND filings, to start phase one trials for all three of our assets, and to see those through to not to completion, but to significant numbers of patients in each of those trials since phase ones typically have an extended tail in terms of their running. Certainly, we'd get through dose escalation for all the programs as well as some initial dose expansion with significant numbers of patients to report out for each of the programs.
Got it. It's fair to say you're going to see the signal from all of those three programs to make the go-no-go or next-step decision with the current cash runway.
Exactly. We are not looking to raise money again until we have clarity of what we are doing next with the portfolio.
Right. That's a true three shots on goal then.
It's a true three shots on goal, which we think is pretty unique and pretty exciting to be part of.
All right. Excellent. That's all from me. Any other questions from the audience? If no, we conclude the session. Thank you, Dave.
Thank you so much, Roger.