Hi, good afternoon, everyone. I'm Tara Bancroft, one of the Senior Biotech Analysts here at TD Cowen. Thank you so much for joining TD Cowen's Sixth Annual Oncology Innovation Summit. For our next session, we have a fireside chat with WhiteHWK. It is a pleasure to introduce Dave Lennon, the CEO. Dave, it's a privilege to have you here. Thank you so much for joining me. Before I get started in questions here, I just want to make sure the audience is aware that if you have any questions, please email them to me at tara.bancroft@tdsecurity.com. I will be sure to get them asked. I guess, Dave, a good place to start would be if you could just first a little bit of background on WhiteHWK Therapeutics. I know it relaunched from the parent company of Aadi.
Maybe a little bit of the thought behind that and even the sale of FYARRO. Just the decision for all of this.
Yep. Happy to, Tara. Thank you for having us today here on the call. It's such an opportune moment right before ASCO, as we all get ready for all the oncology news and meetings that will be coming up. At WhiteHWK, we're really excited. It's actually our first ASCO as WhiteHWK Therapeutics. We are an oncology-focused company developing a portfolio of ADCs for the treatment of various and important cancers. We formed out of a previous company called Aadi Bioscience, which is a company that is still commercializing an mTOR inhibitor called FYARRO, which was approved for a set of rare soft tissue sarcomas. That product was selling about $25 million a year here in the US with plans to expand globally. We also had some negative news around some indication expansions that we were pursuing.
Rather than continue to limp along, I guess, as a small company with a single asset, we look to transform our story. That transformation started with the sale of FYARRO to a Japanese pharmaceutical company who was interested in owning what was otherwise a smallish revenue stream and looking to expand that product globally. We sold with FYARRO, the brand, the associated infrastructure, including a number of employees who went over to support that product, as well as the brand Aadi that went with them. We were then compelled to think about how we would reinvent ourselves as WhiteHWK Therapeutics.
That included utilizing the proceeds from the sale of FYARRO, plus existing cash, plus a fundraising effort we did, which in total brought in a capitalization of about $250 million to in-license a portfolio of ADC assets that we think are truly compelling and on that next-generation wave of innovation for oncology treatments in the ADC field. We officially relaunched in March as WhiteHWK Therapeutics and are now pursuing that portfolio, which we plan to bring into the clinic over the next year.
Awesome. OK. I definitely we have plenty of time to get into the pipeline. I think one of the most interesting things we can hear about next is with the agreement with Hangzhou DAC and WuXi Biologics for the three next-gen ADCs. I think a little background on what kind of experience and expertise that you're bringing in here from not just on the team, but on the board. That would be really helpful.
Yeah. Anytime you make a shift in technology, there's a requirement to really say, well, who is going to do the work? It starts with the fact that we did go to China to source innovation. For all of the discussion about innovation coming from China and the ability to access that innovation, it is still a very difficult and competitive marketplace. Personally, starting with myself, I had the advantage of having lived and worked in China extensively. We used an extensive network on the ground in China to really dig through what we thought were true innovations in the field of oncology. We ended up focusing on the ADC field because we felt like that was an area where we could bring value quickly by transferring those assets into the Western markets. We ended up partnering with WuXi Biologics.
The real advantage there, as you know, WuXi is one of the biggest monoclonal antibody producers that's out there. They have a ton of expertise. They had actually found a collaboration with Hangzhou DAC, who is a leading ADC platform provider. In many ways, WuXi had already screened the entire ADC platform universe and said, these are the partners we want to have in China. That was really reassuring for us. Of course, we did our own due diligence. That just reinforced the quality of innovation in the ADC platform that they had in-licensed. That combined with WuXi's monoclonal antibody experience really gives us this opportunity to bring forward really the leading edge of innovation in the ADC field into our portfolio, which is a global portfolio.
Ultimately, we did, through that network, that evaluation, we identified three really exciting assets based on targets that we think have the potential to be really groundbreaking for patients and important treatments in the future. We will get into the science of those, I am sure. Ultimately, that agreement led to this three-asset licensing agreement for global rights to each of those assets based on the Hangzhou DAC ADC platform. We paid about $44 million upfront for those assets. We have some development milestones, but we think we are in a great financial position to continue to both create value in these assets. We are not limited in potentially doing deals down the road with strategics or other players as these assets grow and develop.
OK. I kind of want to get into the science of the platform. Actually, can you tell us more about how this ADC platform is differentiated from other Next-gen ADCs, either that, yeah, that are also under development, not even just single assets or platform technology? How yours differs from them?
Yeah. I think part of that is an identification of the components of an ADC that are really differentiating. The first is the targeting approach that we choose for the markers that we're looking for within the tumors. The second really is the linker system that is used to conjugate the payload, which is the third component, to the ADC. In each of those cases, we really optimize what we would call the latest technology on each of those aspects to make best-in-class ADCs. That starts with targeting approaches that use high affinity antibodies, but also are very selective in which parts of the molecules that they're targeting within the tumor microenvironment to ensure proper localization of the ADCs to their targets. Hongzhou's linker payload platform, which is consistent across all three of our ADCs, produces a couple of things we think are really important.
First is they're highly stable. Their stability in plasma is as good or better than any of the platforms that have been developed to date. The second thing is that they are cleavable linkers, meaning they can release their payload at the appropriate moment. We think that's intracellularly. We use peptide-based cleavage sites or peptide-based cleavage site for all of our ADCs. They deliver a topo-1 isomerase-based inhibitor payload. There are a couple of different variations of this mechanism of inhibition within cancer cells. We think in our case, we have hit the right balance of one that is highly potent, but also produces a side effect profile that is potentially best in class.
OK. So this stable cleavable linker you mentioned, that's kind of the key feature of the platform, right? Maybe it would be helpful, I think, to learn a little bit more about how, if you could compare and contrast it to more conventional technology, like the Val-Cit linker technology that people have used and exists in a lot of approved products. I mean, how do you, and even more so, how do you then balance stability and cleavability to achieve the desired effects that you're looking to get?
Sure. It is a great question. I think there is often confusion around this topic, right, that people think too much stability is bad and leads to side effects. That is actually not the case per se, right? Stability in and of itself is very good. The question is, does your payload release at the appropriate place within? Accumulation of payload without cleavage is bad. That is where sometimes fixed programs have gotten in trouble in the past. When you look at linker stability, the chemistry of the linker becomes really important, chemistry being the structure of the linker itself, but also the bioconjugation process that is utilized to establish the linkage between the antibody and the linker. In both of those cases, Hangzhou DAC has developed a number of interesting chemistries that allow us to improve upon stability of prior linkers. Some of those are proprietary.
We still have not talked about publicly. One we have talked about is this concept of a carbon bridge that exists between linkers in the Hongzhou platform. The carbon bridge actually exists between two linkers, which creates essentially a third bond tying linkers together at the sites of bioconjugation. What that allows for is if there is loss of any single linker, it is actually still attached to the antibody overall versus singly added on linkers, which if lost, are lost because there is only one point of contact for those types of linkers. That is one aspect that allows us for improved stability. There are a number of other aspects that have been developed within this platform, which we have demonstrated have led to better stability overall and as comparable or better than anything that we have been able to benchmark so far in the marketplace.
The aspect of cleavability is all about the question of where that occurs. There's cleavage that occurs outside of the cell, extracellular cleavage sites. Some people use metalloprotease sites for that kind of cleavage. We are very much in the mindset that intracellular cleavage is the cleanest way to go about engagement at the site of tumor. We utilize a proprietary, again, cleavage site to allow for release at the site and intracellularly within the tumor cell itself, which we think leads to the most potent delivery of the molecule.
OK. Great. Thanks for that. Let's talk about the payload next. I think, is there anything, is this a novel payload, a well-validated payload? I know you said you're using topo. In that too, I am curious if you have any thoughts about existing topo-inhibitor ADCs that are approved and in development, and the indications are expanding for these. How are you thinking about potential resistance developing to topo payloads and where there's still a lot of white space for your ADCs to go?
Right. Let's start with the basic kind of component of payload variation, right? You have topo-based topoisomerase-1 inhibitor-based payloads, which typically are kind of in vogue right now in terms of people utilizing those in the latest programs that are coming both to market and into the development pipeline. Those are largely replacing tubulin inhibitor-based payloads that were part of the first generation, which a number of products got approved, but a number of products also failed because of the limited therapeutic index that tubulin inhibitor-based payloads had. There are a couple of other classes of payloads that aren't as have improved as productive. These are the big two. Certainly, I think when you talk about topoisomerase inhibitor payloads, you're really looking at an improved therapeutic index overall. That has led to more people kind of leaning into this payload delivery.
About half of those programs today rely on what we call pure exatecan-based payloads, which is kind of the generic molecule in the class known to be highly potent. It also comes with some side effect profile that may be more difficult to manage, particularly on heme toxicity. People have then looked for variations of that to see if they can improve upon that exatecan profile. Certainly, there are a number of those. Deruxtecan is probably the most prolific and most successful to date from Daiichi Sankyo. Our program is very similar to DXd in its profile and behaves quite similar in potency, or at least in an in vitro setting, but is proprietary. We believe can lead to the potential for kind of a best-in-class profile from an efficacy and safety perspective. There are variations.
Those are all still to be proven out, as many topo-based payloads still have not read out, even on phase one. There are so many in development right now. There is always that concern then about the question you raised around cross-resistance and what happens. We think there is still lots of space for competition and differentiation, both from a payload-to-payload perspective, target-to-payload perspective, but also just utilization of ADCs in general. If you look at the lung cancer space, for example, there are very few patients that are actually being covered by ADCs today. Most of the progress has been made in the EGFR space, which leads to other actionable mutations in the whole EGFR wild-type patient population without real treatments. It was encouraging to see Taliso V's approval last week, at least getting now into the CMET-positive population.
That is still only about 10%-12% of that EGFR wild-type group. There are a lot of patients still out there who need to be treated. There are a number of indications similar that are just not being covered by ADCs and certainly not by topo-based ADCs. We think there is lots of room to play, especially for our portfolio, which targets a broad range of different indications.
Yeah. That definitely makes sense. OK. Another thing with this platform, I know you mentioned that they have had others in the clinic in China. I was hoping you could give us a little bit more insight to any learnings that you have gathered from those clinical experiences that you feel are important to share.
Yeah. That's something that was important as we went through due diligence is understanding what is the clinical experience with the platform that we're utilizing. And Hangzhou DAC actually has some internal programs which are utilizing the same platform that we are utilizing for our WhiteHWK programs. Those programs are early still. They're still in dose escalation phase. The data we've seen so far indicates that it's performing as we would expect. It's very potent. It has a good tolerability profile. Ultimately, as that data becomes available, I think it'll become clear why we invested in this platform.
Yeah. OK. That's definitely great to hear. I'm curious, now that you are experiencing or just learning a little bit, even in early stages of dose escalation and the Chinese studies, I'm wondering if you have any insight into which preclinical findings you find are translating the best from animal to human.
Yeah. I think the things that we're seeing consistently translate, both across not just in that experience from Hangzhou DAC, but also in our own programs, is that stability that we saw within the platform. That platform stability is very consistent across our programs that we've seen. That's translated across species, which we think bodes well for how the products should perform once put into the clinic. I think that's important to just come back to one of the core reasons we licensed this portfolio was because the targets that we were evaluating all have data that demonstrates efficacy already in prior programs. There's precedent clinical data for each of the targets that we are going after with our three ADCs.
Therefore, what we believe is we need a predictable program that we know how it's going to react, with stability being consistent as one element that we're able to then drive prediction. That should allow us then to translate what was promising early data in those prior precedent programs into really impactful data with our new advanced next-generation ADCs.
OK. I think now is the perfect time to talk about those three next-generation ADCs. I get distracted by the nerdy science stuff. I think it's still interesting to get that perspective as we think about how to assess and predict the therapeutic window and how efficacious, excuse me, that these can be. I think a good place to start on these three assets is a better understanding of what you found compelling about these three targets in particular.
Yeah. There were a couple of components that were really compelling. I think the first, as I mentioned, is this precedent data. We have three targets we're evaluating: PTK7, MUC16, and SEZ6. Each of these targets had big pharma programs where they were generating promising efficacy signal. Because they were utilizing first-generation ADCs, those programs had to be discontinued largely for safety reasons. That gave us a really compelling proposition because we know these targets are validated from a tumor perspective, that if you address them, you will address the tumor. We just needed better ADCs to go do that. I think in each of these cases now with this platform, which I've described to you and described to the audience, we have this real opportunity to build upon those initial efficacy signals.
We think these, therefore, can be best in class against the particular indications we think are important.
OK. I know the INDs for all of these, you're basically planning them in rapid succession through the mid of next year. I guess in the meantime, how can you satisfy our hunger for more data? Are you planning on presenting any more preclinical evidence from each of these at any time in that period of time? If so, what could that look like or include?
Yeah. I think we're in a hyper-competitive space, both from an ADC perspective overall, but even in our individual targets. To some extent, we keep some of our differentiating parts of our profile close to the vest and the data close to the vest at this point in time, especially since we have sufficient capital to continue to prosecute these assets through clinical data. With that said, I don't think you'll hear a lot from us this year about these assets. As we do roll these into the clinic, and just a reminder, we're planning on putting HWK-007, which is our PTK7 ADC, into FIO for an IND in Q4, MUC16 by the end of this year, and SEZ6 by mid next year.
Three programs in the clinic, basically, when we're talking again this time next year, Tara, that we're prosecuting is really exciting. I think around those times, the first half of next year is when we'll also get more data around that to support those clinical programs more holistically.
OK. Yeah. Definitely makes sense. OK. Since you mentioned it first, let's go to PTK7 ADC. I guess it'll be a little while until we see clinical data from that. I think in the meantime, some good context that you could help us out with is how it compares and contrasts with other programs in development. I think Pfizer's definitely a good comparison there, would be helpful. Also, Day One has one as well, DAR-8. Any kind of compare and contrast you could do with those or others would be great.
Yeah. For sure. I think PTK7 is one of those targets that we're going to talk about a year from now as now being more crowded and exciting. I think it's really an emerging kind of area of interest as a number of people have started to develop assets against the PTK7 target. Why? It's one of the most broadly expressed tumor targets out there. It actually can be involved in maybe up to 60%-70% of all cancers. All people who get cancer will have a PTK7 positive tumor at some point. That makes it an exciting value proposition if we can address those tumors and target those tumors with kind of next-generation ADC platforms. Pfizer had a first-generation program. There was a partnership with AbbVie, COVID-2, Zumata, Pelodan.
As I mentioned, promising efficacy data, so 40% response rate in ovarian cancer and PTK7 high patients, 25% in lung cancer. We believe by moving to a next-generation program, you typically see 15-45 percentage points in overall response rate generation. That translates into improved PFS for those patients. We think a next-generation ADC based on PTK7 can potentially beat current standard of care and outcompete a lot of products that are in the pipeline. That is the value proposition that attacking this target has: a huge number of patients that potentially could benefit from this therapy. With our platform, we think really differentiating efficacy. Pfizer fell short. I think where others potentially could fall short is the constructs that are being utilized within the space.
Certainly, as I mentioned, we spent a lot of time really understanding the specific chemistry at each component of chemistry that adds to the profile of proper performance of an ADC. I think when you look at assets that have been licensed by others, they were typically a few years older and utilizing technology that is a little further behind or was a little earlier in its development. Therefore, we should be looking at, well, what is the stability really? What's the affinity and components of their antibody that they're utilizing? I think there you'll see a number of points of differentiation between our programs and those from competitors.
OK. Yeah. We will definitely look forward to that. I mean, speaking of competitors too, like the phase ones, it took more of a pan approach. I guess that makes sense with 70% expression across cancers. And so you.
I do not want to jump in too quickly on this question. But I do think that one of the errors that a lot of drug developers are making these days in the ADC field is thinking, because my tumor target is expressed on a lot of different tumors, I should access all of those and figure out where it works best or those kind of things. What we are finding is that companies, especially small biotech companies who take that approach, generally are not rewarded at the end of the day because what you end up with is showing efficacy in a very small number of patients. So you end up with four or seven responses. And it is just not sufficient information to continue to fund a company, to continue to fund a program moving forward, or to generate strategic interest.
We believe in a strategy that is not an all-comers approach within the phase one program. We are actually relying, not relying, but building on what Pfizer has already done. We think using precedent indications allows us to quickly show differentiation in a meaningful patient population that will allow us to really show what the product can do. People can make the extrapolation to all the other indications where you can potentially benefit. Our strategy will be one where we'll be quickly accumulating a large number of patients in individual indications. For PTK7, that's likely to be in lung cancer and ovarian cancer where the product was studied previously. We believe that's the fastest way to show that this product can be differentiating. If it's not, then we move on to the next product.
That is one of the beauties of having multiple assets within our portfolio. Doing so in the financial mechanism that we did is that we really have three shots on goal with our portfolio. We think all of them can potentially be home runs. Even if only one of them is a home run, it is still a huge value inflection for the company.
Yeah. Absolutely. That rationale definitely makes sense. My unsolicited advice is that you should have the endometrial in there. I think that's really interesting considering how high the expression is in there and the unmet need. No one asked me.
It's great.
I mean.
From your KOL opinion, Tara, it's great you're very aligned to a number of feedback we're getting in the marketplace. It's something we're looking at right now is that endometrial indication amongst the gynecological community is one where they see a lot of potential value for ADCs to come into play. Certainly, we're very excited by the PTK7 story in endometrial where there is very high expression relative to ovarian.
Yeah. Definitely. You know, I know we let PTK7 excitement get away from us. I know the MUC16 and SEZ6 programs are also really exciting. I am sure that we will have plenty of opportunities to discuss those in the future with you. We have gone a little bit over time. I really do appreciate you giving your time to us, Dave. I appreciate everyone here listening.
Thank you so much, Tara.
Thank you, Ari.