Welcome everyone to Jefferies Global Healthcare Conference 2026. My name is Roger Song, Senior Analyst covers mid-cap biotech. It is my great pleasure to introduce our next company, Sutro Biopharma, having a fireside chat with the CEO, Jane Chung, Jonathan. Jane, why not you give us a state of our Sutro. We have a lot of things can talk about, the most exciting kind of data readout in my coverage, I would say, in the coming weeks. Yeah, Jane. Yeah. Great to be here with you, Roger, and at Jefferies. We are very excited with the momentum that the Sutro company has been delivering. When we made this big pivot last year, last March, we had committed to three programs getting into the clinic in three years, now we're on track after transforming our business, to delivering three programs into the clinic in two years. We're accelerating our pipeline. We've reduced and streamlined our operations, we're very excited with our first program already into the clinic. It's a tissue factor ADC, where we get to see our ultra design capabilities of four ADCs. Our technology is very unique. It's a platform that can deliver on very differentiated programs because we have the ability to optimize every component of an ADC, including the antibody, the linker, and the payload, and the sites of conjugation and how everything is combined, which is very different from conventional ADC companies where they focus on one or two features. This is when you can design something to be really meaningfully different, and we have, in a very short amount of time, built a pipeline that is very differentiated as well. It includes two single payload ADCs that go after complex targets, which are, we say they're complex because they're expressed on both normal tissue and cancer tissue, and you need to be able to strike the right balance while also delivering on a very potent payload. In addition, we feel that we can contribute to the future field of the ADCs with the innovation that we have, designing our dual payload ADCs. This is what's next. What's the big step next in terms of ADC innovation? Resistance, we believe, to ADCs will be driven not by target, but more by the payload class, and so we're already developing and discovering the next generation of payloads as well as combination strategies to deliver in a targeted way. Excellent, Jane. I have to say this, Sutro is my number one covered company as a Senior Analyst. It's been a long road. I've been working on this like 10 years. And then Jane, I give you the kudos to how you transform Sutro, and then with the new management team as well. Sutro has a very unique cell-free synthesis kind of platform. I think it's very powerful. We all know Vaxcyte stories are coming literally coming from that platform. It's been a long road, but right now it seems you are cracking the nut to developing some next gen or if not, third or fourth gen of the ADC, with a couple pipeline in the clinic and with tissue factor ADC as the lead. Maybe we focus a little bit more today's conversation on the upcoming data readout midyear tissue factor ADC. We put out a preview note earlier after talking with you as well. What should we be focusing? Because we want to set the right expectation. It is early days. It's a dose escalation, but also seems this messaging is pretty encouraging. You've been talking with the street, this is you want to widen the therapy window. You want to address the safety issue while maybe you are trying to achieve the anti-tumor activity even beyond the cervical. Give us some high level, and then we can ask some more questions. Our tissue factor ADC is designed, it's a β-glucuronide DAR 8 exatecan payload ADC. How we're designing our ADCs is fundamentally different. We are trying to optimize both for efficacy as well as safety. I think many ADC companies have moved to the Topo I payload class as sort of the next generation payload, but they're also designing for safety. They're choosing lower potent exatecans, like a deruxtecan or a belotecan, or taking the DAR from DAR 8 down to DAR 6 or DAR 4. When you design only for safety, primarily, you're actually leaving efficacy on the table. Sutro, we've selected the most potent payload of exatecans and keep it at the DAR 8. Even with our dual payloads, we're going up to DAR 10 with PTK7, and even with the ATR combinations, we're going up to DAR 16 and possibly DAR 24. We're going in the opposite direction. The reason we believe we can do that is because we've actually achieved highest non-severe toxic doses at a very high level for even our tissue factor program at 50 mg/kg, even on a single payload basis. This is higher than what conventional ADCs have achieved. If we can strike the right balance of delivering more payload, more potency, and at the same time, delivering more safety, this is how we believe we can maximize or widen that TI, right? With tissue factor. We've made a lot of improvements from our first-generation program we had before. We have moved to the more potent exatecan payload, kept it at a DAR 8. We've improved the linker strategy with a beta-glucuronidase linker that has been modified for our cell-free system. It's not something that you can cut and paste and put into a CHO-based manufacturing system. We have made our optimization with click chemistry, with our non-natural amino acids that is highly stable, but it cleaves more in the tumor and less so outside the tumor. That leads to a better safety profile, leading to a lot less platform toxicity. In addition to that, our antibodies are made in a cell-free system, so they don't have the cell membrane. They're not glycosylated. They're not sugarized, they don't engage with Fcγ receptors th at are in the lung or in the eye, and again, improving the safety of our antibody that we make for the ADC. Again, we're dialing up the safety, but we're also dialing up the potency, and this is why we believe that we can meaningfully differentiate the benefit to patients with this kind of design features. Okay. Right. You try to achieve both ends. That's a big mission to achieve, but you may be able to do that. Maybe on the safety side, maybe tell us about the dose level you are right now, which is already very impressive. How should we think about the safety profile compared to the first-gen tissue factor and maybe also the Topo I or exatecan at the payload? How are you going to address, kind of compare, benchmark to both end? Yeah. Compared to the approved tissue factor program, it's TIVDAK, it's a tissue factor ADC approved in cervical cancer. They have an HNSTD of 3 mg/kg. The STRO-004 program we're developing for tissue factor has a HNSTD of 50 mg/kg. We have changed the payload from a tubulin payload to a Topo payload. We have optimized our linker strategy from a val-cit/val-ala linker to a beta-glucuronidase linker. We have made our antibodies in a cell-free platform, which does not in and of itself engage with Fc gamma receptors. We know, looking at the BLA for the TIVDAK program, that the antibody alone, this tisotumab, actually can contribute to some of the ocular toxicity. In terms of enrollment, where we are for the phase I trial, we have already shared that we have cleared and completed dose level three back in February and March. We continue to escalate, and we're ahead of projections in terms of execution. We'll share more later this year. Maybe, Jonathan, you want to share how it's going on the trial? Yeah, thanks, Jane. The trial has proceeded faster than we expected. We're ahead of schedule. I think that's in no small part due to the investigators having their confidence built by a very, very strong pre-clinical package. Jane's mentioned that the HNSTD was 50 mg/kg, and to come back to something that Roger mentioned about anticipated safety, what we didn't see in the GLP tox study were any of the expected toxicities associated with TIVDAK. While obviously it would be foolish to ignore the experience of TIVDAK and not monitor for bleeding, eye events, et cetera, we'd actually didn't observe those in the GLP tox study. I think the investigators read into that this is a very well-designed drug, which has been as well prepared as is possible to get a new asset into the clinic. When their confidence is up, they get enthusiastic about enrolling. That keeps the study moving at a high pace, and I think the midyear data readout that Jane will talk about will be compelling we hope. I do want to say that tissue factor is expressed in normal tissue, so if you go really high on the drug exposure, you're likely to see that. Again, it's the benefit-risk ratio that we're looking for. If you're able to really dial up the drug exposure in a much more powerful way and deliver more drug and more potency, then you have to evaluate the opportunity. I would also say the momentum that we have in our phase I trial has been very strong. The fact that we're continuing to escalate and we are moving at the pace that we are and had committed to actually getting to data midyear, and getting there. We only started this trial in December, it's only a few months before. Being able to execute this way can almost suggest that you're not running into the DLTs that's stopping you from escalating. Right? There's definitely momentum and excitement around this program. Yeah. No, I totally echo that. As you do the phase I, dose escalation, typically those trial are going to wait a year or something to read out, and then you committed very early on, right? You say, "Midyear, we're going to have data." Still kind of confirming that, though that's very encouraging, which I totally agree means you don't have any stopping and then also progress very rapidly. Maybe just stay on that point. In terms of the midyear update, how much the robustness of the data we're going to see in terms of the end, dose level, tumor type, right? I think a couple of things that you can give us some color. Yeah. I think for any dose-finding trial, the primary goal is to see if we have a drug that works, and how to understand the data that we're seeing in context, right? We're going very quickly. Obviously, there's several different dose levels that we're going to study here, and getting to a good look of data so that we could have some good understanding of the safety of the human PK parameters. What is the optimal sort of drug exposure needed in the humans? We have a lot of elegant preclinical work. How does that correlate? Any early activity that we see across different tumors will be very encouraging for us at this point. Again, I think the whole strategy in this tissue factor ADC program is to deliver greater benefit beyond cervical cancer. We know cervical cancer is a high unmet need. The opportunity may be shrinking given the vaccine and the developments and advancements made there. If we can, and we've seen some programs actually show some data in other tumor types with this approach. It's very encouraging for the field. I think at this juncture, depending on how high we're able to deliver on the dose, any activity in other tumor types will be very, very encouraging for the program. Also how high we're able to actually get the drug exposure. I think that is also an indication for TI, right? We're excited to see the data progress. Yeah. We know you're clear the dose level three, February, March, you're moving to that level four. You start with 1 mg/kg? Oh, yes. Yeah. We did start with 1 mg/kg. Yeah. It's interesting, there are other tissue factor programs that have just revealed their data. We know TIVDAK started at 0.3 mg/kg. Evopoint's data that was highlighted at ASCO, they started at 0.6 mg/kg. We started at 1 mg/kg, which I don't think should be under-recognized if you will. This is a new platform with a new linker payload system. We had no questions from the FDA to start at that higher dose. Yeah. Good. Despite tissue factor being expressed on normal tissue. Got it. You didn't say what's the dose level two, three, or the plan the highest dose? Jonathan, do you want to take that? No. As before, no. I tried. I tried. I know. That's good, Roger, but I will say it's a pretty solid dose escalation, and you aim for your top level in dose escalation to be often aspirational. Yeah. We're making strong progress. Got it. In terms of the protocol is a 3+3 dose escalation. No. Okay, tell me what's a protocol backfill? Okay, just to cover the dose escalation, it's not a three plus three. It's a modified TPI. The significance of that is it gives you a flexibility over enrollment numbers, so in fact you can push the numbers up. The second thing is the FDA have given clear guidance that they approve of backfill cohorts because it allows you to build out your safety and tolerability profile at relevant doses so that you don't get sort of surprised later on by some new event because of insufficient numbers. The way you're going with this, Roger, is how many patients in the mid-year update? Okay? It's not a three plus three, so that means it's going to be more than 12 patients. Even our heroic investigators couldn't enroll 100 by mid-year. It'll be a number somewhere between that very wide range, which I know causes some irritation. We can't, again, for competitive reasons, we can't reveal exactly how many patients we're going to have mid-year. I think, as I said before, Jane wouldn't have said it, that we're going to have a mid-year data release unless we plan to make the data compelling. Something that people can buy into. Got it. Because we saw you mentioned a couple, TIVDAK and then some other tissue factor ADC, we can talk about that later. I mean, since the dose level seems they are getting to two or three level, they become even like approve the dose, the pivotal dose. How you think about, because the potency is a lot higher for STRO-004, how we think about the therapeutic level? It is one is potentially can be the therapeutic level or it's kind of later, next? The PK from the animal studies told us that we're delivering highly potent drug with very limited unscheduled release of payload into the circulation. That is certainly the cornerstone of reducing platform toxicity. Again, that comes back to all the design features that Jane mentioned. We anticipate that the platform tox question will be answered early on with STRO-004, and that of course will have a read-through into the whole rest of the program because the beta-glucuronide linker is, if you like, our secret sauce to some extent. That's an important feature. We'll be very much looking forward to sharing PK data in the mid-year data release along with safety. As Jane said, we're already looking for activity because every patient coming into the dose escalation has to have measurable disease. Before handing it back to Jane and Roger, I will just also add that remember that the data we'll be releasing mid-year is an entirely U.S. study. You won't have to sort of weigh up, well, what does this mean translating a China study into the West? This is a study performed in the West, the data will be very easily intelligible to the Western investor audience. Just to add here, the 1 mg dose that we looked in the preclinical work was a very active dose. That said, we have in our phase I program heavily treated patients, right? You have to see whether or not that translates into that kind of patient population. Any activity that we see would be very encouraging, even at those low doses. Yeah. We'll come back to this expectation to the anti-tumor. One, just like I said very early on, we need to set the right expectation, right? In terms of the tumor type, we understand this is a phase I dose escalation, like Jane said, it's heavily pretreated. The tissue factor approved in cervical, which probably makes sense for people understand this could work. You have like seven or six other tumor types, and then how should we think about those tumor types potentially will be more in the trial? Because we see the PDAC, we have some head neck in the past. I think TIVDAK in the early day, I think we look at the phase I, it's kind of a six, seven tumor types. Seems these are all widely expressed. In your trial, how much you can say at this point in the tumor type distribution? Maybe I'll start and hand it to you, Jonathan, about the kinds of patients we're seeing in the phase I. I would say that the approved TIVDAK program achieved in their phase I program, if we harken back to what's an apples to apples comparison, if you will, not that this is what we see as the benchmark, but this is just a comparator. When they first started their trial in phase I, they achieved one PR in 27 patients, and that PR was in cervical cancer. It took them two years to get there. We're committing to getting to data within six months or a quarter of the time. We're looking at activity beyond cervical. It should be very valuable for us to really understand what this program can do. In the trial, we have eight different tumors that we're looking at. Phase I tend to be more heavily enrolling on the panc side of things and pancreatic as well as CRC, just because of the limited treatment options they have in standard of care. That said, we'll have representation of all eight of them so far in the phase I. It's just basically how many patients can we really analyze the data with. I know everyone asks me, what's the benchmark? What's the ORR benchmark? It's very hard to do when you have one or two patients within a cohort or within the study representing that tumor. We have to see and understand the data in context of what we're seeing. If we're seeing greater activity with higher dosing and greater exposure, that's a good thing. If we're seeing safety balanced on the dose exposure, that's also a very good thing. If we're seeing anti-tumor activity broadly, that's a good thing as well. Maybe you want to add to that, Jonathan? Thanks, Jane. I mean Roger, that basket of indications is wide, and I think that speaks to the fact that one of the problems in the ADC space is not the lack of targets. We have good targets, and tissue factor is an excellent example. All the tumor types in the basket of escalation could have a forward development path if we see signals. I want to underscore that. We have got representation in those indications in the escalation study. As Jane said, the heavy lifters in all phase I studies in the U.S. are pancreatic and CRC, but we are seeing the other tumor types as well. This is important for us. The other important thing is that because people ask is, "Well, what about the tissue factor expression?" We are collecting specimens. It's an eligibility criterion to come into study that you have to have tissue available for analysis. The reason for that is not that we're looking to make a companion diagnostic. Our premise is that by getting a high DAR, high potency payload ADC, that we can go after the lower expressers. We want to show that, and we need to do that by doing at the back end expression versus response. We are collecting tissue, but we're anticipating strong activity at all levels of TF expression. Got it. Yeah. I think we took a look at the same thing for TIVDAK early trial and then across different tumor types. As you said, Jane, if the N is so small, honestly, we should not look at the individual tumor. Rather, it's a broad kind of a look. If you have activity or tumor shrinkage, not necessarily response, and across all the tumor type, that can be very encouraging in terms of the anti-tumor activity. I think so. You're looking at directionally what you're seeing in the patient population that you're also looking at, right? We allow for up to 14 lines of therapy so these patients are very heavily treated. I get it. Folks are focused on a ORR bar from other cohorts, and that's easier to do when you have a specific indication and you have like 30 or 40 patients you're looking at in maybe a very specific line of therapy, whether it's second line or third line. We have potentially up to four or five or six lines of therapy that patients would be treated. It's very hard to understand what is the true benchmark. That being said, we're being very thoughtful about the data that we're seeing, not only in the past with TIVDAK, but also emerging tissue factor programs. We will be making sure that we can deliver on a competitive profile. We're looking also on whether the study, the drug is worth continuing to develop. That is the central question for us. We have three programs going into the clinic. We have to manage our investments moving forward. So far, we have not seen anything to tell us that it's not something we should do. Yeah. Yeah Excellent. I think that's a perfect time to wrap up the STRO-004 is this is the first look. You also want to make this readout meaningful, which can inform your next step. What would be considered as an overall profile you think that's good investors, we also yourself and then say, "Okay, we should move forward," and then what will be the next step and maybe that's a follow-up? To amplify Jane's point, when you do a phase I study, until you have the patients in and look at their data, you don't really have their profiles fully worked out. We need to sort of parse the data very carefully to understand what we're getting. A very obvious point is prior irinotecan exposure, which we've seen, I think, heavily influence the Evopoint data. We need to understand all that. Then we need to demonstrate that the PK has performed as we expected it to from the GLP tox study. Remember that the antibody that we're using in STRO-004 does cross-react with cyno, which I think lends weight to the GLP tox study that it will be reflective of where we go in the human. We need to confirm that, and then as Jane has alluded to, we need to confirm that we know we have succeeded in widening the therapeutic window. That's important because always in oncology you treat to tox. If the patient has no tox then you're always wondering if you've left exposure on the table, that you could've given more, you could've got more responses. If the therapeutic window is wide, everybody gets treated to a dose that is known to have some incidence of tox, but knowing that when you do have to dose reduce, you can dose reduce to a level where you still have activity. That's one of the benefits of the therapeutic window is it allows more patients to benefit. Yes, some will get tox, but when you dose reduce them, they're still getting a meaningful level of drug exposure. That will be an important concept for us to confirm early on. Yeah. We have one of the strongest scientific sort of preclinical work for this program. We looked at the PK, we looked at the HNSTD. We have done about 100 PDX models where we look at robust samples of PDX, not just models that are sensitive for a specific payload or whatnot. We're taking a very scientific approach to this evaluation of this program. So far the data tells is very encouraging for us. We've even benchmarked our PDX to the competition. We see things that are very correlative in the clinic. Now, we're excited to get to data so that we can actually correlate our early preclinical work to the clinical data. If this does work, this is probably one of the most exciting things that we can be doing because this methodology that we've introduced can actually de-risk every program in our pipeline. This is very valuable because I know when folks go to different conferences, there's 300 posters on a new ADC. How do you tell the signal from the noise? You have to take a very scientific, realistic approach on what a drug can do. When you look at the parameters of objective PK, when you look at the HNSTD, which we have been very transparent on all of our data, and you do the kind of PDX modeling where we look at a robust sample, but we give one dose of a clinically relevant dose as opposed to 15 mg or 20 mg, which can show that any drug works in a PDX model. We're not trying to fool ourselves. Really we are excited to see whether we can actually translate this into the clinic and it will be powerful for not only STRO-004 but STRO-006 and STRO-227. Excellent. All righty. I think we talk enough about STRO-004. We just look forward to the data. I think you will deliver what you want to achieve and as you already told us, so far, nothing really prevents you to continue the development, and I think we feel your confidence. Okay? Maybe just the last minute in terms of financially, where's Sutro at? You also alluded earlier, you have a slew of the pipeline based on the same platform, right? Yeah how much more you want to tell in a year, to you. With our recent raise of $110 million earlier this year, that now affords us to actually study all three programs, STRO-004, STRO-006, and STRO-227, and getting into the clinic and getting to POC. This is very important and valuable for us, having multiple programs, getting into the clinic, to validate the science and the technology. Prior to the raise, we were really looking at STRO-004. All eyes are on STRO-004 for everything, but now we have the money and the funding to do that. We have the cash out to Q2 of 2028. This affords us to do great science. Excellent. All right. Thank you, Jane. Thank you, Jonathan. Thank you everyone listening and watching.