Ted Tenthoff, I'm a Senior Biotech Analyst at Piper Sandler. Before I begin, I'm required to point out certain disclosures regarding the relationship between Piper and our next presenting company, Sutro, which are posted at the back of the room and at the registration desk. Sutro is developing next-gen antibodies using its XpressCF cell-free platform, or XpressCF platform. I've known this company for a long time. This is actually an IPO that I did. The company's really gone through a lot of changes. I think if you give it a fresh look today, you're going to like what you see. The company plans to file three INDs over the next three years. Or actually, they've already done one of those, STRO-004, which is in the clinic, tissue factor ADC, as well as an integrin beta-6 ADC next year, and also their first dual payload ADC, which I think is a really, really interesting approach targeting PTK7. The company's also partnered with Astellas, developing immunostimulatory ADCs. Here from Sutro is Jane Chung, CEO, and also Jonathan Fawcett, Vice President of Clinical Development. Thank you both for being with us. Thank you. So as I started to mention, you guys have been working on this XpressCF platform really for over two decades now, and I think have made just substantial progress in terms of what you're able to generate from this platform. Maybe you can start off by describing what are some of the unique characteristics and advantages of the antibodies that you're producing? Yeah. So first, thank you for the opportunity to be here at this conference with you, Ted. And we are making some really significant progress in our pipeline. Just to take a moment to describe our unique platform, we have this ADC technology that enables us to actually increase ADC drug exposure about two to three-fold higher than conventional ADCs. We do this by optimizing every component of an ADC, from the antibody to the linker to the payload. And in addition to that, we actually have site-specific conjugation. Now, I know that's a buzzword in the ADC field, but our binding, we have these non-natural amino acids, which we use in the cell-free system that allow us to position our linker warhead on any site of the antibody, which actually improves the performance of our programs. And that is really. We're trying to design medicines that really can be very transformative and actually dial up the differentiation of the products we can actually make with our platform versus conventional ADCs. Now, we have single payload ADCs that go after really hard-to-reach complex biology targets where there's less competition and also have large market opportunities for us. So it's high value for Sutro. And then on the dual, we also have dual payloads, which very few companies have the protein engineering to be able to be so sophisticated that you can incorporate two different payloads onto an ADC to really dial up the efficacy and improve the performance of these programs, which we think can actually be the next sort of stage or next frontier of the ADC field. Why? Because we want to overcome resistance to single payload ADCs. We see the kind of single payload sort of exotic ADCs coming from China, sort of the window sort of closing. This is really designed to overcome sort of single payload ADC resistance and actually replace some of these therapies as best-in-class standard of care therapies in the future. Yeah, absolutely. It's really an exciting time. And I use the word next-gen a lot. In the case of what you guys are doing, it really, really stands out and is pronounced to me. And I think back to the early days of ADCETRIS with Seattle Genetics, which I used to cover, and the toxicity associated with that payload falling off before it even got injected and DARs all over the place. Again, hats off to them for starting and pioneering this field. But we're really seeing, and your characterization of optimizing each piece really resonates with me. You guys are back in the clinic conducting a phase I study of a tissue factor ADC, STRO-004. Tissue factor is a validated ADC target by Tivdak. How is STRO-004 different? And where do you think you can improve, again, on that first-gen ADC? Yeah. So first, I think it's a really important milestone for the company to be back in the clinic six months after we made a strategic pivot back in March. This is a lot of execution. We have transformed our business in a record time. And actually getting back into the clinic and showing that we can validate the platform with clinical validation is really important for us. We've extended the cash three times this year by reducing the burn and externalizing our manufacturing. And we're also bringing timelines in. So we're actually delivering more value for our shareholders and for patients moving forward. On the tissue factor STRO-004 program, we feel that we have designed a program that is highly differentiated for both safety and for efficacy. As I mentioned earlier, we design these things by optimizing every component of the ADC. So the payload we've upgraded to a DAR8 Exatecan payload. We've actually made payloads up to DAR16 without compromising PK. But for this payload, we have made a DAR4 version and a DAR8 version. And the DAR8 version actually shows more anti-tumor activity in a broader set of tumors beyond cervical at half the dose of the DAR4 version. And that's why we wanted to make sure we selected the DAR8 Exatecan. We've upgraded the linker strategy to a beta-glucuronidase linker, which is further stabilized with our non-natural amino acid in our cell-free click chemistry. So it cleaves better in the tumor and less so outside the tumor, again, improving the safety window of our program. And then on the antibody side, we have actually selected an epitope that actually doesn't interfere with anticoagulation factor X or VII, which also then improves the safety profile of our program. And it's selected for high internalization for tissue factor. So these and one additional thing is we actually do site-specific conjugation as well. So again, it's not restricted to the cysteine or lysine conjugations. And again, it can actually improve the performance of this program. All of these design features are meant to really dial up the safety of the program. We have an HNSTD, or highest non-severely toxic dose, of 50 mg/kg. That is one of the highest safety doses, highest doses we've tested for an ADC out there, even in conventional ADCs. At the same time, when we look, that's half the equation from a safety perspective. When we look at efficacy in our PDX models, we're looking at doses as low as one milligram per kilogram that actually gets us to anti-tumor activity in our PDX models. So there we see, wow, you're getting really strong anti-tumor activity even at those low doses, but the safety window is really high. And this is, again, it expands the therapeutic window of our programs. Yeah, very, very cool. And really appreciate the attention on each aspect of the ADC. Now, you guys just announced this morning that you've already dosed the first cohort of patients. So not the first patient, first cohort in the phase one study of STRO-004. Tell us about how enrollment's going so quickly. What's the enthusiasm that you're seeing from the sites? When could we get our first look at data? Yeah. So we're very excited to be back in the clinic. We actually got IND clearance at the end of October. Within a few weeks, we actually activated the first wave of clinical sites. And then we achieved our first patient in the study. And today we just announced that we actually treated the first cohort of patients, which is a lot of execution in building a very strong momentum for this trial. I'll pass it to Jonathan to kind of speak to the development plan and our progress so far. Thanks. And echoing Jane Chung, thanks for the opportunity to join this discussion. You asked about how enrollment goes so fast. I mean, that depends, it really depends on the sponsor-investigator relationship. You have to work hard to build those relationships. And then really the asset speaks for itself. If the preclinical package looks convincing, I mean, we're working with investigators who are very deeply familiar with ADCs, and they like what they see. And they want to be part of the journey to discover just what potential STRO-004 can realize. Because the preclinical package is so strong, we've been able to enter dose escalation at one milligram per kilo. And that's significant because it allows us to enter at a point where we already know from preclinical studies that that level of exposure has you very close to being therapeutically active. It takes a very small number of steps to get up to exposure where you get to explore the early potential of the drug quickly. On top of that, at Sutro, we do believe strongly that this is a targeted therapy, and we should be going to tumors even in dose escalation where there's a reasonable expectation of the target being present. And that also gives us a greater opportunity for an early look at anti-tumor activity. So harnessing the investigator enthusiasm, a very pleasant outcome from the FDA regarding our dose escalation strategy allows us to execute a plan where we anticipate top-line data, the first top-line data by the middle of next year. Yeah, incredible. You know, Jonathan, it really triggered a thought because I was wondering if just these centers too have gotten so much more sophisticated as well. So it's not just the drugs that you guys are bringing forward, but their knowledge of how to administer them, of how to handle side effects, all of these things. I really hadn't appreciated just how much the clinical field, the sites have advanced in terms of their familiarity. So I have to imagine that's something you're seeing too. Completely right. And that's why you work very carefully to develop relationships with investigators, because they have to trust you. They have to trust that your preclinical package is not going to spring some terrible surprise on them in the clinic. And again, we absolutely rely on their enormous skill in exploring what a new drug can do because they have to be very, very alert, and they have to be very slick at managing situations in general. And they understand too that speed is important, that we do need to get enrolled quickly. And again, as I said before, if they hike the asset, your job is half done for you in that regard. Yeah, very cool. Now, Jane, I don't think you've mentioned all of the cancer types that you're going after. Tivdak is approved in cervical. Do you envision the ability of taking STRO-004 beyond cervical? And where might some of those other disease areas be? Yeah. So the goal of the program for our tissue factor program is to expand the opportunity beyond cervical. Obviously, we include cervical because it will be a good proof of concept that the product actually works in cervical as well because it's highly expressed, and tissue factor is highly expressed in cervical cancer. But it is to really expand the opportunity well beyond. And the fact that not every company actually discloses their starting dose for a phase one program. And we're being really transparent here that we're starting at a relatively high dose. If you recall what Tivdak did, and their starting dose was 0.3 mg/kg. They have an HNSTD of about 3mg/kg. So in comparison, our HNSTD of 50 mg/kg allowing us to actually start much higher. The fact that we've actually dosed the first cohort and expect to actually get to the second dose level before the year end, we are moving with speed with this program. We want to make sure that we actually get the clinical validation. Now, we also did some really extensive PDX work. We shared it at our R&D day. We looked at 20 different PDX models. We're not cherry-picking models here. We're looking at extensive PDX models where we look at really studying STRO-004 and where the possible sort of responses will come. We've seen very encouraging responses in pancreatic, in lung, in head and neck, and even in colorectal. We only had one model, but it was a complete response rate. So I don't want to underestimate that. We're very excited about the emerging preclinical data set. It's one of the strongest data sets we have seen, and we're very excited to validate the program in the clinic. Yeah, really cool. Now, you guys hosted R&D day online. I'm sure it's posted on the website. If anyone hasn't seen it, take a look. One of the programs that you highlighted was this integrin beta-6 ADC, STRO-006. What can you tell us about this target? And why does it make sense to go after? Why does it make sense for you to go after it with an ADC? Yeah. So integrin beta-6, historically, this has been a difficult target to make. Our CSO, Hans-Peter Gerber, who we hired with many years from Pfizer and Seagen, had shared with us that it took almost 10 years for Pfizer to kind of make this program. And so with our very powerful protein engineering, we've been able to make this in a record time. And it's really the balance of being able to identify and select for a heterodimer, this alpha-v beta-6 specificity that is involved in tumorigenesis without getting involved in the integrin beta family of receptors that are nearby. And so you want to make sure that you're striking the right balance going after the tumor cells, but not necessarily impacting normal cells. And so we are excited about this target because it's already been validated in a phase three program in non-small cell lung cancer by Pfizer. They show about a 30% ORR. I think it's a VC-MMAE construct in terms of design. I think there's much more improvement that can be made in terms of improving the side effect profile. This lung cancer is a huge opportunity, high value, big clinical unmet need, and makes sense for us to actually go after this target. When do you think you could take 006 into the clinic? We're looking at an IND for Integrin beta-6 ADC next year and clinical data after that. Great. Very exciting. Another one to keep our eye out on, and another topic that you guys talked about at the R&D day that I think is just really, really differentiated. I know that some of this originally started with work with Astellas, but this concept of dual ADCs, and we talked about it very briefly, but I'd love to dig into a little bit more on this. How are they able to improve efficacy? Yeah. So dual payload ADCs are supercharged ADCs where you combine two different cytotoxic payloads onto an antibody. We know that resistance is driven less by the target or loss of target and more by the class of payload, as evidenced by the fact that you have a lot of HER2 treatments that patients get treated with sequentially. So it's not necessarily about the target. It's really about the payload. And so I think, and now we are even seeing some new emerging data that shows that an Exatecan ADC followed by another Exatecan ADC shows really limited benefit. So what's next after an Exatecan ADC? We also know that chemo combination can be more effective than single-agent chemotherapy. And dual payload ADCs is simply targeted delivery of chemo combination. And so we're very excited about this opportunity to actually bring something that's highly innovative and that could really take the ADC field even further. Yeah, really cool. And I think the lead asset that you mentioned, STRO-227, targets PTK7. Tell us a little bit about this target and how you designed STRO-227. Yeah. So PTK7 is an attractive target to go after from an ADC program. It is expressed on cancer cells in ovarian, lung, and breast cancer, but is also expressed in cancer stem cells. And we know this in that if you remove cancer stem cells from a tumor, they stop growing. So this can be really exciting for us to be able to show a promising program after this target. It has been validated clinically already with the Pfizer program. Cofetuzumab pelidotin actually showed about 20%-30% ORR, but the PFS was a bit shorter, again, limited by toxicity. There was a recent Genmab program that was discontinued because it was a VC DAR-8MMAE and again, too toxic. But I think several companies are going after PTK7 with a single Exatecan payload construct. That's why we believe that going after this with a dual payload construct is highly differentiating and will bring a best-in-class potential to compete against those. You know, beyond one of the concepts today introduced is that even beyond increased efficacy, these dual ADC payloads can also be safer. So maybe lay that out for us because it's kind of a conundrum. Typically, we see increased efficacy and increased toxicity. But how do you really kind of rectify those two factors? Yeah. It's actually the most important question to ask as it relates to a dual payload ADC because you're right. You think of more drug, less safe. I think this is why the Sutro technology is uniquely enabled to make the dual payloads because we have not one, but two non-natural amino acids by which we stabilize these linker payloads to the antibodies, and we can fine-tune and tightly control the ratios of these payloads. These payloads are not equal in potency or equal in safety, so you have to fine-tune them. You have to adjust the ratios, and not a lot of technologies have the sophistication to be able to do that well. And so even with our programs for PTK7, we show that they're very well tolerated at doses as high as 25 mg/kg, which is almost equivalent to what you would get from a DAR-8 Exatecan ADC single payload. So this is why we're excited about the ability to actually deliver a safe combination with a dual payload. Yeah, really exciting. Now, one of the things that you worked on, I mentioned this briefly, is with Astellas, you're working on immunostimulatory ADCs. And this is one of the first applications where you guys were looking at dual payloads here. It's a chemo plus an immunostimulating agent. Tell us about sort of the premise here and what you guys are working on with Astellas. Yeah. So I think the ADC program is an example of the dual payload construct. Here, we combine an immunostimulatory agent with a cytotoxic payload, one by activating the immune system to actually have a synergy with the cytotoxic payload. We see that even with anti-PD-L1 chemotherapy, and here we are now learning more about the immunostimulatory agent we use as a STING. And we're seeing a cross-talk and actually a synergy between STING and topo 1s. And this actually helps with internalization of the payload into the tumor, as well as sensitizing the tumor to topo ADCs. So this could be a very exciting program. We are very excited about the Astellas partnership, and we're excited to see their first program go into the clinic early next year. Yeah, very cool. In early 2026. So we're just about out of time. You talked about the work that you've done to kind of extend the cash runway. I think you guys ended the third quarter with somewhere around $168 million. How long does this fund the company? What's it enable you to accomplish? Yeah, so we've done some really hard work this year to transform the business. We've extended our runway three times. Now it's into the middle of 2027. It doesn't include all of our milestones with our partnerships, and so there's opportunities to further extend the runway to give our data more time to mature, to validate our programs, and we are in active discussions around BD, but I don't guide to that as well, but there's a lot of interest on the dual payload side as well, but we're doing a lot here. In this year, it's been a very transformative year for Sutro in 2025. We've transformed the business. We're back into the clinic six months after the pivot. Next year, we'll have about three more programs into the clinic. We are going to be a full-fledged clinical oncology stage company with multiple shots on goal to validate our science, and this is really exciting for us. Yep. Awesome, well, again, if you haven't taken a look, take a look at the new Sutro. I think you're going to like what you see. Thanks, Ted. Thanks, Ted. Thanks, Jonathan. Thank you.