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Welcome, everyone, to Jefferies' 2026 Global Healthcare Conference. My name is Roger Song, Senior Analyst, covers Semicat Biotech. It is my great pleasure to introduce our next company, Sucral Biopharm, and then having a fireside chat with the CEO, Jane Chang and then Jonathan. So Jane, so why not you give us a state of art for Sucra? We have a lot of things we can talk about, and the most exciting kind of data readout in my coverage I would say in the coming weeks and then yeah so okay yeah so great to be here with you Roger and at Jeffries we are very excited with the momentum that the suture 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 and now we're on track after transforming our business to delivering three programs into the clinic in two years. So we're accelerating our pipeline. We've reduced and streamlined our operations, and 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 an ADC 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, very different from conventional ADC companies where they focus on one or two features. And so 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-pay load ADCs. Again, 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 for 10 years and then Jay I give you the how you transform Sutro and then with the new management team as well Sutro has a very unique self-free synthesis kind of platform I think it's very very powerful we all know backside stories literally coming from that platform So it's been a long road, but right now it seems you are cracking the nuts to developing some next gen or if not a third or fourth gen of the ADC with a couple pipeline in the clinic and with tissue factor ADC as the lead. So maybe we focus a little bit more today's conversation on the upcoming data readout mid-year, tissue factor IDC. We put out a preview note earlier after talking with you as well. So 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 that you want to widen the therapy window. You want to address the safety issue while maybe you are seeing the, you know, try to see, achieve the endotumor activity even beyond the cervical. So give us some high level, and then we can ask some more questions. Yeah, so our tissue factor ADC is designed. It's a beta-glued DAR-8 exotecan payload ADC. How we're designing our ADCs is fundamentally different. We are trying to optimize both for efficacy as well as safety. And I think many ADC companies have moved to the topo payload class as sort of the next-generation payload, but they're also designing for safety. They're choosing, like, lower-potent exotecans, like a Derax tecan or a Bella tecan, 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 exote cans and keep it at the DAR- 8. Even with our dual payloads, we're going up to DAR 10 with PTK-7, and even with the ATR combinations, we'RE going up to Dar-16 and possibly Dar-24. So we're going in the opposite direction. And 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 milligrams per kilogram, even on a single payload basis. So this is higher than what conventional ADCs have achieved. And so if we can strike the right balance of delivering more payload, more potency, at the same time delivering more safety, this is how we believe we can maximize or widen that TI, right? And so 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 exotecan payload, kept it at a DAR. 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. And 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, and so they don't engage with FC gamma receptors that are in the lung or in the eye, and again, improving the safety of our antibody that we make for the ADC. So 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, so you're, you try to achieve both ends, so that's a, that's a, big mission to achieve, but, you know, you may be able to, to do that, so maybe on the safety side, so, maybe tell us about the dose level you are right now, which is already very impressive, and then, how should we think about the, the safety profile compared to the first-gen tissue factor, and maybe also the topo-1 or exotican at the payload, how How are you going to address, you know, kind of compare benchmarks of POSAND? Yeah. So compared to the approved tissue factor program, which has a, it's TIBDAC. It's a tissue factor ADC approved in cervical cancer. They have an HNSCD of three milligrams per kilogram. The STRO4 program we're developing for tissue factor has a HNSCT of 50 milligrams per kilogram. We have changed the payload from a tubulin payload to a topo payload. We have optimized our linker strategy from a Valsit-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. And so we know, looking at the BLA for the TIVDAC program, that the antibody alone, this to Sodimab actually can contribute to some of the ocular toxicity. And so in terms of enrollment, where we are for the phase one 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, and maybe, Jonathan, you want to share some, how it's going on the trial? Yeah, thanks, Jane. The trial has proceeded faster than we expected. We're ahead of schedule, and I think that's in no small part due to the investigators being, having their confidence built by a very, very strong preclinical package. Jane's mentioned that the HNSTD was 50 milligrams per kilogram, and to come back to something that Roger mentioned, you know, about anticipated safety. What we didn't see in the GLP tox study were any of the expected toxicities associated with TIFDAC. So while we're, obviously, it would be foolish to ignore the experience of TIFBAC and not monitor for bleeding, eye events, et cetera, we actually didn't observe those in the GLP TOX study. And I think the investigators, you Know, read into that that this is a, you know, a very well-designed drug, which is, you you know, has been as well-prepared as it's possible to get a new asset into the clinic. And so when their confidence is up, they get enthusiastic about enrolling. So that keeps the study moving at a high pace, and I think, you know the mid-year data readout that Jane will talk about will be, you now, will be compelling, we hope. But I do want to say that, you know, these are tissue factor is expressed in normal tissue, so if you go really high on the drug exposure, you're likely to see that. But again, it's the benefit-risk ratio that we're looking for, and 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 1 trial has been very strong. And the fact that we are continuing to escalate and we are moving at the pace that we were had committed to actually getting to data you know mid-year you know and getting there like we only started this trial in December so it's only a few months before and so being able to execute this way can can almost be suggest that you're not running into the DLTs that's stopping you from escalating right so there's there's definitely momentum and excitement around this program. Yeah no I totally echo that so as you do the phase one those escalation typically those trial going to wait a year or something to read out and then you committed it very early on right so you see a media we're going to have data and then still kind of uh confirming that though that's very encouraging which you know totally agree means you don't have any stopping and then also kind of progress very rapidly so maybe just stay on that point so in terms of the mid-year update how much the uh the robustness of the data we're gonna see in termsof the end those level tumor type right so i think a couple things that you can give us some color 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 so we're going very quickly obviously there's several different dose levels that we'll 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? And then any early activity that we see across different tumors will be very encouraging for us at this point because, again, I think the whole strategy in this Tissue Factor ADC is to deliver greater benefit beyond cervical cancer. We know cervical cancer is a high unmet need, but the opportunity may be shrinking given sort of the vaccine and the developments and advancements made there. So if we can, and we've seen some programs actually show some data in other tumor types with this approach, and so it's very encouraging for the field. And 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. And also how high were able to actually get the drug exposure. I think that is also an indication for TI, right? So we're excited to see the data progress. Yeah. And then we know you cleared the dose level three, February, March, and moving to the level four. And did you start with one milligram per kilogram? Oh, yes. We did start with 1 milligram per milligram. It's interesting. There are other tissue factor programs that have just revealed their data. We know TIBDAC started at 0.3 milligram per diagram. EVA points data that was highlighted at ASCO, they started at 0.6 and we started at one milligram per kilogram which I don't think it should be under under recognized if you will this is a new platform with a new linker payload system and and we had no questions from the FDA to start at that higher dose yeah despite despite tissue factor you know being expressed on normal tissue got it and then you but you didn't say what's that those level two three or the plan the highest dose as before no that's good Roger but it's it I will say it's a pretty it's pretty solid dose escalation and you know you aim for your top level and dose escalations to be often aspirational so we're making strong progress got it and then the instance of the the protocol is it's a 3 plus 3 dose escalation, but also, okay, so tell me, what's a protocol, backfill, and then the... Yeah, okay. So, I mean, just to cover the dose escalations, it's not a 3 Plus 3. It's a Bayesian-designed modified TPI, and the significance of that is it gives you a flexibility over enrollment number, so you can push the numbers up. And 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. So, you know, because the way you're going with this, Roger, is how many patients in the mid-year update? Okay, so it's not a three plus three, so that means it's going to be more than 12 patients. But, you Know, even our heroic investigators couldn't enroll 100 by mid- year, but it'll be a number somewhere between that very wide range which I know causes some irritation but you know we can't again for competitive reasons we can reveal exactly how many patients we're gonna have mid-year but I think as I said before Jane wouldn't have said it that we're gonna have a media data release unless we plan to make the data compelling you know something that people can buy into got it and then the internet because we saw you know you mentioned a couple chip deck and then and some other tissue factor ADC, we can talk about that later. But in the instance of dose level, it seems they are getting to two or three level, they are kind of become even like approve the dose, the pivotal dose. So how you think about, because the potency is a lot higher for O4, how we think about the therapeutic level? It is one is potentially can be the therapeutic level or it's kind of a later, next? I mean, 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, and that is certainly the cornerstone of reducing platform toxicity. And so, again, that comes back to all the design features that Jane mentioned, and so, you know, we anticipate that the platform tox question will be answered early on with And that, of course, will have a read-through into the whole rest of the program, because the beta-glu-linker is the sort of, you know, if you like, our secret source to some extent. So that's an important feature. So we'll be very much looking forward to sharing PK data in the mid-year data release, along with safety. And as Jane said, you now, we're already looking for activity, because every patient coming into the dose escalation has to have measurable disease. I will just, 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, so 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, and so the data will be very easily intelligible to the Western investor audience. And just to add here, the one milligram dose that we looked in the preclinical work was a very active dose. But that said, you know, I think we have, in our phase one program, heavily treated patients, right? So you have to see whether or not that translates into that kind of patient population. So any activity that we see would be very encouraging, even at those low doses. Yeah, so we'll come back to this expectation in the anti-tumor. One, just like I said very early on, we need to set the right expectation, right, so we can summarize everything we discussed later. And then in terms of the tumor type, we understand this is a phase one dose escalation, like Jane said, you know, it's heavily pre-treated. And then the tissue factor approved in cervical, which probably makes sense for people to understand this co-work. And then 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 and neck in the past. And I think TIPDAC in the early day, and then we look at the phase one, it's kind of a six, seven tumor types. So it seems these are all widely expressed, but in your trial, how much you can say at this point in the tumor type distribution? So maybe I'll start and hand it to you, Jonathan, about the kinds of patients we're seeing in the phase 1. I would say that the approved TIBDAC program achieved in their phase 1 program, if we hearken 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 but when they first started their trial in phase one they achieved one pr in 27 patients and that pr was in cervical cancer now it took them two years to get there and so we're committing to getting to data within six months or a quarter of the time and we're looking at activity beyond cervical so 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 ones 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 one. And it's just basically how many patients can we really analyze the data with. So I know everyone asks me, what's the benchmark? What's the ORR benchmark? But it's very hard to do when you have one or two patients within a cohort or within a study representing that tumor. So we have to see and understand the data in context of what we're seeing. You know, if we're seen greater activity with higher dosing and greater exposure, that's a good thing. If we're saying safety balanced on the dose exposure, there's also a very good thing if we are seeing anti-tumor activity broadly, that's a good thing as well. So maybe you want to add to that, Jonathan? Yeah, 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. So, you know, I think that's, I want to underscore that. And we have got representation in those indications in the escalation study. As Jane said, you Know, the heavy lifters in all phase one studies in the U.S. are pancreatic and CRC. But we are seeing the other tumor types as well. So, You know, this is important for us. And the other important thing is that, because people ask is, well, what about the tissue factor expression? We are collecting specimens. You know, it's an eligibility criterion to come into study that you have to have tissue available for analysis. And 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 expressors. And so, you know, we want to show that, and we need to do that by doing at the back end expression versus response. So we are collecting tissue, but we're anticipating strong activity at all levels of TF expression. Got it. Yeah, so I think we took a look at the same thing for TIFDAC early trial and then across different tumor types. And, you know, as you said, Jane, if the end is so small, honestly, we should not look at the individual tumor. Rather, it's a broad kind of, you now, kind of look. And then if you have activity or tumor shrinkage, non-necessary response, and across all the tumor type, that can be encouraging in terms of the anti-tumor activity. Yeah, 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 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. But we have potentially up to four or five or six lines of therapy that patients would be treated. So 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 TIVDAC, but also emerging tissue factor programs. And so we will be making sure that we can deliver on a competitive profile. We're looking also on whether, you know, the study, the drug is worth continuing to develop. That is the central question for us. And we have three programs going into the clinic. We have to manage our investments moving forward. And so, so far, we have not seen anything to tell us that it's not something we should do. Excellent. I think that's a perfect kind to wrap up the O4 is this is the first look, right? But you also want to make this readout meaningful, which can inform your next step. So what would be considered as an overall profile? You think that that's good, investors, and we also yourself, and then say, okay, we should move forward. And then what would Be the next step? And maybe that's the follow-up. I mean, to amplify Jane's point, you know, when you do a phase one study, until you have the patients in and look at their data, you don't really have their profiles fully worked out, so we need to sort of parse the data very carefully to understand what we're getting, and a very obvious point is prior or inner TCAN exposure, which we've seen, I think, heavily influence the EVO point data, so, you've got to understand that, and then, you We need to understand all that. And then we, you know, we need to demonstrate that the PK has performed as we expected it to from the GLP TOC study. Remember that the antibody that we're using in strophol does cross-react with the syno, which I think lends weight to the GLT TOC Study, that it will be reflective of where we go in the human. But we need confirm that, and then we need, as Jane has alluded to, we have succeeded in widening the therapeutic window. that's important because always in oncology you treat to tox. You know, if the patient has no tox, then you're always wondering if you've left exposure on the table. You could have given more, you could have got more responses. But 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 so that 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 and they're still getting a meaningful level of drug exposure so that will be an important concept for us to confirm early on we have one of the strongest the most scientific sort of preclinical work for this program. We looked at the PK. We looked the H and SCD. We have done about 100 PDX models where we look at robust samples of PDX, not just, you know, models that are sensitive for a specific payload or whatnot. taking a very scientific approach to this evaluation of this program. So far the data tells is very encouraging for us and we've even benchmarked our PDX to the competition and 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 and 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. And 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. And when you look at the parameters of objective PK, when you look at the HNS CD, 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 milligrams or 20 milligrams, which can show that any drug works in a PDX model, we're not trying to fool ourselves. And so really, we are excited to see whether we can actually translate this into the clinic, and it will be powerful for not only stroke four, but stroke six and 227. Excellent, all righty. I think we talk enough about all four. We just look forward to the data. I think you will deliver what you wanna achieve, and you already told us so far, nothing really prevent you to continue the development, and I think, we feel your confidence, okay? And then maybe just last minute, in terms of, you know, financially, And then you also alluded earlier, so you have a slew of the pipeline based on the same platform, right? I think, you know, how much more you want to tell in the use of the MiniL2? So with our recent raise of $110 million earlier this year, that now affords us to actually study all three programs, Stro4, Stro6, and 227, and getting into the clinic and getting to POC. This is very important and valuable for us. multiple programs, getting into the clinic to validate the science and the technology. Prior to the raise, we were really looking at Stro4. All eyes are on Stro4 for everything, but now we have the money and the funding to do that. And we have the cash out to Q2 of 2028. And so this affords us to do great science. Excellent. All right. Thank you, Jane. Thank You, Jonathan. Thank everyone listening and watching. Thank you.