Good morning, everyone. I'm Tara Bancroft. I'm one of the senior biotech analysts at TD Cowen. Thank you so much for joining TD Cowen's sixth annual Oncology Innovation Summit. For our next session today, we have a fireside chat with Sutro, and it's my pleasure to introduce Jane Chung, the CEO, and Hans-Peter Gerber, the CSO of Sutro. Jane and Hans-Peter, it's very much a privilege to have you here, and thank you so much for joining me. Before we get started, I do want to remind anyone that's listening that you can email me questions at any time. My email is tara.bancroft@tdsecurities.com. If you have any questions, I will make sure to get them asked. I think, Jane, a really helpful place to start would be to kind of review the recent strategic changes that you've made. You know, I know that people who have been following Sutro for years, they know you've helped Luvelta. Can you go over really what the decision was that you made, what informed that, and where you're going from here on that program? Yeah, so Tara, thanks for having us here. We enjoy being part of this conference. To your question, the board and the management have conducted a very strategic review of our business and evaluated all options to drive shareholder value. In the process, given sort of the pipeline that we had emerging in our next generation ADCs with the improvements that have been made in the platform, we concluded that the best way to drive shareholder value is to advance the second and third generation ADC pipeline. That is really the crux and the reason why we're making this pivot with the company. Although we are deprioritizing the development of Luvelta, despite the clinical activity that was seen, we have learned a lot of lessons and insights that can be leveraged into the pipeline around product design, our manufacturing, as well as our acceleration to clinical POC in terms of our clinical strategy. All of that are good insights that will help us actually de-risk our future programs and actually continue to drive value for shareholders. Okay, thanks for that. You know, even with it being deprioritized, do you plan to share any more data or updates from that, like this year, next year, at any time publicly? Is that mostly just going to be a strategic focus on the side for you guys now? We will be continuing to, we are still in active discussions around partnerships. And so we will be continuing that effort moving forward. Okay. All right, great. Thank you. I think the most productive use of this very short time we have here today will be to talk about the ADC pipeline now. You know, I think a good place to start would be just kind of high level from a platform perspective. What do you think differentiates your approach with this pipeline versus the several other companies and platforms that are developing next gen ADCs as well? I think in that, getting some context of preclinical data that you've shown would be really supportive and helpful. We have at Sutro one of the most powerful ADC technologies that can optimize every part of an ADC, from antibody to linker to payload, all at the same time. We have designed our next generation ADCs to target hard to reach complex biology targets, as with both single payload and dual payload ADCs. These are not easily made from conventional manufacturing. This is really what will differentiate our products in the future and also show a meaningful differentiation in our platform. We are also very excited, especially excited about the dual payload ADCs, because these can actually overcome resistance to single payload ADCs in delivery of not just targeted chemotherapy, but targeted chemo combination therapy. Sutro has the opportunity here to be the first to really show the use of these multi-payload ADCs in the clinic. This is what we are really excited about. Maybe Hans-Peter, you want to add some excitement, your excitement as well to the platform and technology? Yeah, I'm happy to provide some additional insights here. Looking back in the last 20-25 years of ADC development, as you may have realized, there was a major breakthrough about five years ago with Enhertu where we had much better response rate in a variety of indications using an exatecan payload. The benefit of this new technology is really on the safety part of the entire ADC. We learned with our platform using that same payload that we can dose much higher compared to competitor ADCs using the same linker payload class. This is really getting back to where we started at Sutro. It's a unique manufacturing system. We're the only ones that manufacture ADCs in cell-free extract. We can do more things faster than other platforms. We optimize the therapeutic index, in particular on the safety side, so we can dose about twofold higher than other competitor ADCs with the same linker payload class in cynos. We are now looking forward to seeing how that translates into the clinic. In addition to these safety improvements that really stretch the TI on the bottom, so we can dose much higher without seeing toxicity, we are now learning how to use this technology to combine two payloads, so three payloads on the same ADC, dual payload, triple payload ADCs. We are now learning that the major breakthrough, even in the dual payload class, will be again on the safety side, because you could argue that, yeah, sure, two payloads, you are going to get more activity, but you are going to get more safety. We just finished a couple of cynos tox studies, and we see that we can already dose much higher with a DAR4 tubulin inhibitor and with eight TOPO-1 added compared to anybody else could ever dose with DAR4 MME, for example. We are super excited to expand our advantage that we see with exatecan ADCs to dual payload ADCs. We think that it is going to be a massive improvement and benefit for patients to have this safe technology, dual payload, that you can dose much higher than single payloads, for example, in cynos and hopefully also in patients. We are super excited to actually see that translate into data in cynos and hopefully soon. Things look good that as you know, we're going to be later in this year, we're going to be in the clinic with our first DAR8 exatecan targeting tissue factor. Okay, yeah, I want to spend a good amount of time on Sutro for the tissue factor ADC. Just, you know, to stay on this topic, and it's very clear from hearing you guys speak about how excited you guys are about the dual payload ADCs that you guys are discovering and developing here. I'm curious, you know, when we speak, as you've already mentioned, you know, when we speak to KOLs or experts in the field, one of the potential fears or concerns that they have is the additive safety from the two different payloads. I'm curious then, if you could be more specific on what exactly gives you confidence in the safety advantage here. Is it payload choice? Is it the DAR? Or what is just a couple more specifics on that would be great. Yeah, yeah, no, we have reviewed this a couple of times. It goes like this. There are six different aspects, key aspects on the safety side that you can engineer. It goes all the way from the target selection, all the way to linker payload, all the way to where you place your payload. The key drivers of safety that we have an advantage over is really that we manufacture in these cell-free extracts. One byproduct of this manufacturing method is that we do not glycosylate our antibodies, so they cannot bind to Fc gamma receptors. Our ADCs do not bind to Fc gamma receptors. These receptors are expressed on a variety of normal cells. Actually, these normal cells internalize an ADC, and that can lead to platform toxicity, including ILD, for example. It's been published by Daiichi that the Fc gamma receptors mediate the ILD that you see TOPO-1 ADCs in the lung, particularly in lung cancer. When we did our cynos tox experiments, we did not see ILD in this cyno species, even though at these levels you should see it. We are very encouraged that we may have lower ILD levels. That is one out of six. The other main differentiator of our platform is that we are using this beta-glue linker, which is slowly getting popular. I I think there is about 70% or 80% of all ADCs used to conventional VC. These are protease-cleavable linkers or GGFG as used in Enhertu. These linkers are prone to be cleaved in the bone marrow. As a side product, you see this neutropenia or pancytopenia with exatecan ADCs when you dose them in patients or in cynos. With the beta-glue, they're not, this linker is not cleaved in the bone marrow. We don't see pancytopenia at very high dose levels, including 50 mg per kg of a DAR8 exatecan. We've done this four times in a row. We've never seen cytopenia or pancytopenia. We are away from these platform toxicities that limit the dose escalation of conventional ADCs. These are two out of six where we have advantages. These cell-free extracts allow us to position the linker payloads very precisely on the antibody that we fear other, that we can avoid interference with other biological aspects of antibodies such as Fc gamma or FcRn interaction, which regulate the half-life of ADCs. We positioned our linker payloads so that they don't interact with FcRn. We have industry best, industry highest PK. In addition to that, we have less of the on-target or platform toxicity. These are three out of six. I could go further, but these are the kind of key hallmarks why we see this massive jump in safety and exposure of our ADC platform compared to conventional ADC platforms. Tara, that was a lot of technical advantages. I tried to summarize that our technology is able to optimize every component of the ADC production, right, from the antibody to the linker to the payloads. The ability to actually engage multiple payloads is not an easy thing. You've got to make sure that you've got the therapeutic window right. You're combining two very toxic payloads. The safety component is going to be important as we look at these things. I think the proof is in the pudding when you come to the preclinical data. What we're seeing is about two to threefold higher PK, as HP alluded, Hans-Peter alluded to. That leads to greater exposure and with greater safety. That can translate into really bigger benefits into the patients in the clinic. In addition, we're seeing some emerging data for our preclinical assets going up to doses of about HNSTD or highest non-severe toxic doses up to 50 mg per kg for some of these assets. That is the highest dose we've seen in non-human primates or NHP models. This is really significant. Again, can translate into bigger benefits for patients in the clinic. Yeah, definitely. I feel like we could spend this whole half hour just going into full nerd mode on all of these different components. I do want to get to Sutro for, but just kind of one more question on that before we move on. You know, it definitely makes sense, the glycosylation, it can improve ILD and another parent molecule related safety, and the linker not being Val-Cit can improve neutropenia. Like payloads, you said exatecan can also improve the neutropenia. I'm curious, like if you're using, say one of the payloads is exatecan, are there payloads that would go better with it versus others? How do you know which payloads will have more additive or synergistic safety properties? Yeah, no, this is a good one. The question is basically when you have all these tools, how do you know, how do you select the right tools to get the optimal therapeutic index improvement? We are doing a two-pronged approach to find the right combination of linker payloads. We are anchoring on exatecans because they have really made a quantum leap in ADC efficiency. We are using exatecan and then combined with another player. One of these players is we went empirical. What are the most successful linker payloads out there? 70% of all approved ADCs are VC MME. We picked MME just to make sure we are not missing the obvious. We are looking at biology. TOPO-1 inhibitors interfere with DNA repair. We're adding a second payload that blocks any DNA repair pathways in the cell that the tumor could engage to overcome ADC treatment with exatecans. There are obvious targets in the DNA damage response repair pathway, ATR for example, or PARP. We published on that already. The third bucket will be to combine again more of the empirical approach to most successful classes of therapies in oncology. It's checkpoint inhibitors, AI immune activators, and exatecans. We already have a collaboration with Astellas on these payload classes combining immune activators with exatecans. We are currently running very late stage programs and experiments with the dual MME combination with exatecans. We actually just presented for the first time, I think anybody has ever presented data like that, that with this combination, exatecan and tubulin inhibitor, in particular MME, but we tried another one, we could overcome ADC resistance in preclinical models, models that were resistant to Enhertu, that is an exatecan ADC, and also tubulin inhibitor ADC. When we come in with the dual payload, we completely regress these tumors that became resistant in the mice over a year time. We use a dual payload and they completely regress. This is the kind of things we see for the first time. We get super excited because this is now clinically relevant. This is what you see in what is reported at ASCO and at ACR that in clinical cancer centers where they have multiple ADCs to treat patients that when you repeatedly treat the patient when they relapse on the first ADC with the second ADC with the same linker payload class, they do not respond to the second ADC. If you switch the second ADC to a different linker payload class like a tubulin inhibitor, they respond to the second ADC as if they had not seen a first ADC. If you have to, there is an emergence of resistance to linker payload in the clinic. We already showed that with a dual linker payload class, you can overcome that resistance no matter what the previous ADCs were, even two ADCs, the patient would relapse. It is likely that it would respond to a dual payload class. This is kind of opening really the door to the next generation of ADCs when the first wave is gone and the patient relapse, they are all looking for a dual payload. That is really more like the five-year goal what we have. The question really is now that we are enabled by our technology to mix these linker payloads to get the best combination, like what is done for chemotherapy, by the way. It is not a new principle. We are just following what already works. The question is, and in analogy to what happened with HIV, where they realized they need to block three protease to actually reduce the viral load, to actually keep the viral load in check, do we need three linker payloads? Do we need three different chemotypes or payloads to keep the tumor under control for a longer period of time? That is more like a long-term stretch goal. Of course, our technology enables us to ask these questions faster and more efficiently. As you already heard, with a very good safety margin, we can explore these spaces knowing that we do not get many hits in the safety aspect. We are exploring that space currently. Tara, to get back to your question, we're going to take a data-driven approach to understanding which is the best combination and which is the safest combination, more effective and safe to put into the clinic. I think no other company has this many modalities of payloads, as well as the ability to fine-tune the ratio of these combinations of payloads. I think those are going to be really important to get to the sweet spot in terms of therapeutic index and a high-performance therapeutic index for these products. I think the other thing that Hans-Peter mentioned is these new resistant models, these models that are resistant to Enhertu. This is where the field is going eventually when more of these ADCs get approved and resistance to these agents will happen. We're not curing folks with these ADCs today. That, but going up against sort of a resistant model to Enhertu, giving us the potential to have a best-in-class product options is really quite exciting. Yeah, definitely agree. I guess that would, what you just said would kind of underlie why you're also pursuing the possibility of the three payload versus two. You think that's mostly the resistance-driven? Because as you said, you saw complete or near complete regression with just two in an animal model, yeah? Yeah. If you think about it, as Dr. Hans-Peter Gerber alluded to, this is no different than chemo combinations, right? You're just giving it in a targeted way. It's a way to overcome resistance with a combination of chemotherapy. Yeah. Okay, great. All right. I think now we can move on to STRO-004. You know, I know this is, as you said, it targets tissue factor. To my knowledge, there's one approved ADC, Tisotumab vedotin. Can you maybe just kind of compare and contrast how you design STRO-004 with at least that molecule or other tissue factor targeting molecules that are currently in development? Yeah. Hans-Peter, maybe I'll go over the design and then pass it to you in terms of why we selected the target. Our STRO-004 is a tissue factor DAR8 exatecan. It has site-specific conjugation as well as a proprietary beta-glue linker as compared to the approved tissue factor ADC, which has a tubulin inhibitor payload and it's a DAR4. We think the structure and design is differentiated. Tissue factor is a challenging and complex antigen target. It is widely expressed in many different tumors, but it's also expressed in normal tissue as well. You want to make sure that you avoid those on-target liabilities. It's involved in coagulation and factor X activation in terms of bleeding. It is also expressed in the skin, tissue factor is expressed in the skin and the eye. You want to avoid, in designing an ADC, you want to avoid those on-target liabilities as well as liabilities that are exposed from other ADCs in terms of neutropenia, as Hans-Peter just alluded to. HP, do you want to get into our excitement around the tissue factor program? Yeah. No, absolutely. The first two targets here that are coming towards the clinic, tissue factor and integrin beta-6, these are known as targets with complex biology. That means the targets on their own, they signal in normal tissues like during tissue repair, tissue factor is involved there. If you use a blocking antibody or a targeting antibody against a target, you want to avoid interference with this biology function and just use it as a basically internalization mechanism for the linker payload, but not to interfere with biology. Because of, again, back to our platform, we can screen our libraries to find the right antibodies or 10 to the 12 using phage display to do that. These libraries are a million times larger than conventional methods to find these antibodies. We were able to actually raise these antibodies and avoid this liability by screening against benchmark. We actually seen the liabilities in our competitor molecule. We screened as long as we found one that doesn't interfere with that biology. Tissue factor, the same of integrin beta-6. That's why we decided to go with mono payloads on those two targets, because it's very hard to get these antibodies against these targets. It's actually, if you look around, there's few competitors in that space because you cannot just copy-paste the antibody. You have to make a new one and super hard to get those two. The next ones on dual payload were going into the bigger target space where everybody is because we're going to be differentiated alone by the dual payload combination that nobody has on any of these targets right now in development. We're going to be the first on those broad and big targets to advance dual payloads. For those first, we just saw that the advantages of our high throughput screening methods allowed us to get these antibodies that are clean, that do not interfere with biology and internalize very efficiently. We think we have enough differentiation on these two targets to be. This concept is not new. If you look around in the ADC field, everybody takes a target where an MME is already approved and that is the safer payload. We are doing the same, but we are adding a lot more safety to each of these ADC that were differentiated from the others. Yeah, that is basically the concept there. Okay, great. I think, I mean, gosh, we are very quickly running out of time here, but I guess the best thing to talk about with the remaining minutes that we have left is, one, what do you have left to do to further the progress along towards phase I? Once it is in phase I, what is that going to look like in terms of which types of patients that you're going to recruit and what you could be expecting from any phase I data, when it could come, like next year or maybe the year after or whenever that is? Okay, so that's three questions in one, Tara. We're on track for STRO-004 to file our IND in the second half of this year, get into first-in-human studies before the year end. I think in terms of the phase I trial itself, we haven't really disclosed specifics around that, but we see that tissue factor is a validated target. Obviously, there's an approved medicine in cervical cancer and early signs of activity in head and neck. We think with the higher exposure we're seeing in the greater PK that we can actually go beyond cervical and get into other solid tumors. I think, in terms of our phase I trial, yes, it's really designed for safety and looking at, and we discussed a lot of the sort of on-target toxicity liabilities. We want to avoid liabilities in the skin, in the eye, in reducing bleeding events as well as neutropenia, all at the same time maintaining good anti-tumor response as well. Given the higher exposure we're seeing with the tissue factor program, we are very confident that we could actually see potentially anti-tumor response as well. Yeah. Perfect. I want to add a bit more detail. We always use higher exposure of tissue factor ADC compared to the already approved ADC out there, Tisotumab vedotin. Putting that in numbers, the number is 50. We got 50-fold higher exposure with our exatecan ADC compared to the published data for that competitor molecule. The good news is usually that translates into patient benefit. The higher you can dose, the more ADC you get into the tumor. We are super excited about this differentiation going forward. I just wanted to add some numbers behind because everybody in the ADC field now says higher exposure, better TI. If you really look at numbers, I think we are very confident that this will translate into patient benefit at the end of the day. Great. Yeah, thank you so much for that. I guess maybe if we could possibly steal 30 more seconds of your time, I do want to give you guys a chance to talk a little bit about STRO-006 as well, which will be afterwards, but still is an exciting target as well. Just kind of what you're thinking about your confidence in that program too playing out as well. Yeah, so STRO-006 also is an exatecan and DAR8 beta-glue linker program. It is differentiated from the competitive landscape as well. It's a very hard, difficult target to make. As Hans-Peter alluded to already, this target is expressed in many solid tumors, but it is highly expressed in lung cancer. It will be a big commercial opportunity potentially. We are very excited about the differentiation we can see in the antibody that we've selected, but also on the safety side. We talked about higher exposure. We also do not see, importantly, ILD associated here. You do not want to see ILD in lung cancer as well. Hans-Peter, did you want to make any comments with respect to this program? Yeah, this is very relevant. The lack of ILD that we see on integrin beta-6 and all the toxicity that have been reported for this already phase three BCMMA ADC developed by others. The one thing, the ILD aspect of that is really critical because when talking to KOL in the lung space, they're saying that the major breakthrough for ADCs in lung will be going to first line. The way to go to first line is to avoid ILD. The current crop of ADCs, including other exatecans targeting crop two or so in lung, they suffer from a twofold higher ILD rate in lung compared to other indications. Because if the lung is already injured, then the likelihood of ILD development is higher. The way to first line in lung will be by having low ILD. Again, with our platform, we do have lower ILD. We've seen that now three or four times in a row. In cynos, we never see ILD. It is very interesting for us to explore that space, of course, late stage, and then all the way into first line, if possible, in combination with checkpoint inhibitors because ILD, the lower ILD levels that we see preclinically may help us getting there. Ultimately for the patient benefit, of course, when you can do that. Okay, great. This sounds all very exciting. We really look forward to hearing more on your progress throughout this year, next year, and throughout the future. Just thank you so much for taking the time to educate us on this today and for spending the time with us. To everyone for listening, thank you so much. Thank you. Thank you for having us.