Good afternoon, everyone, and welcome to the Inaugural Life Science Conference for Citizens here in Miami. It's my pleasure to introduce the next presenting company, Sutro Biopharma. Jane Chung is the CEO, and a company that we cover and recently upgraded. Welcome, Jane. Really appreciate it. You know, I never know exactly who's in the audience, who's listening to the webcast, who may or may not know Sutro, so I always like to start these conversations off with maybe a two-four minute overview of Sutro Biopharma. Yeah. Great to be here with you in Miami, one of my favorite cities. Wonderful opportunity to share the overview on Sutro. We have a new strategy moving forward. We're an oncology ADC company, and we have a very unique ADC technology that enables us to optimize every component of an ADC. It really helps us dial up the differentiation of our medicines to address really high unmet needs for clinical and commercial opportunities. The company last March, when I became CEO, has undergone a massive transformation, and we are looking to advance our early pipeline, which we believe we've incorporated all the advantages of our cell-free ADC technology to really differentiate the medicines that we're going to develop. Let's jump right into it. Yeah. You guys are one of a handful of pure play ADC companies as far as I'm concerned. You know, we have Whitehawk Therapeutics, we have Mersana that just got acquired, you know, you guys, as well as others. Maybe we can talk a little bit more. You mentioned it in your overview a little bit, but maybe dive a little bit more into the platform and what truly differentiates you from others that are in the field. What do you think are the critical factors in terms of developing ADC assets? Yeah. What makes Sutro really unique and differentiated is that we actually make our ADCs and antibodies in a cell-free system. What we try to do here is optimize every component of the ADC, from the antibody to the linker to the payload, and the combinations in which these elements are combined. All of this to say is that we wanna drive up the ADC drug exposure, and what we find in our preclinical work is that we're driving up ADC exposure two to three fold higher than conventional ADCs made through CHO-based manufacturing or CHO-based development processes. I think really the power of this technology to be able to do this iterative design capability is what we're trying to really deliver on. We did this massive pivot last March, and to say that we would be back in the clinic in six months is in record time. Now we have three programs that are heading into the clinic, multiple opportunities to validate the technology, the science, and what we believe will be very, very differentiating for the field. One is already in the clinic. Yes. Right? Let's talk a little bit about STRO-004. Yes. This is against tissue factor. Can you give us an overview of the molecule? You know, what's the DAR? What's the linker? And probably very important, and I think the audience should know is there's already a tissue factor. ADC out there. How are you differentiated? Yeah. We have optimized the design of STRO-004, which is our tissue factor ADC program. We've optimized the payload system to a DAR 8 exatecan payload. The exatecan payloads are a bit more potent than the other sort of modified exatecan payloads, and we've kept it at a DAR 8, so highly potent. At the same time, we know this payload is less damaging to the eyes compared to the Tivdak program or the approved tissue factor. Again, we are able to dial up the potency but also manage the safety of the program. In addition, we've optimized the linker strategy to a beta-glucuronidase linker that is better cleaved inside the tumor and less so outside the tumor, which leads to less sort of platform toxicity in normal tissue. In addition to that, all of our antibodies that we make are Fc silent, and they are made in the cell-free system. The antibodies are not glycosylated or sugarized, and they don't engage with Fc gamma receptors in normal tissue, which avoids liabilities like ocular toxicity and ILD and pneumonitis. This is a real advantage, especially when you're going into therapeutic areas like lung cancer. We feel like we've optimized every component of these. In addition, our site-specific conjugation is not actually restricted to cysteine or lysine attachments. We have the ability to actually conjugate to multiple sites within the antibody that leads to better performance in PK, better safety, and potentially better efficacy. When we think about, you know, Tivdak already being there, you guys coming kind of right behind it, how do you plan on kind of threading the needle, if you will, to develop this as a successful drug? Yeah. Tivdak is a great drug. It actually is approved in cervical cancer, has actually shown some early signs of activity in head and neck and other tissue factor programs have shown signs of activity in pancreatic. I would say that, you know, however, the HNSTD for Tivdak is 3 milligrams per kilogram. In their phase I clinical trials or even at their phase III clinical trials, they couldn't get past the 2 milligrams per kilogram. That's their approved dose. Compared to that, the STRO-004 program is our DAR 8 tissue factor ADC. We have an HNSTD of 50 milligrams per kilogram, which is one of the highest safety ceilings we've seen with an ADC with a very potent DAR 8 exatecan payload. I think here, we are also seeing antitumor activity as low as 0.5-1 mg/kg in the preclinical models, and we have disclosed that we actually none of our competitors have really shown or disclosed their starting dose in their phase I, but we've disclosed that it will be 1 mg/kg, and that is really something that we're excited to see advance. We think that we have sort of met the balance of the sort of higher safety window, but also getting to an antitumor activity potency that will deliver on a best-in-class profile for tissue factor. Now, as we think about this idea of kind of threading the needle in terms of do you go after. I I guess my follow-up to that is do you go after a similar indication? Do you go after new kind of indications where Tivdak hasn't been evaluated or can't be evaluated given the toxicity profile? How do you think about that as you move forward? Yeah. I think for us, tissue factor's expressed in a broad set of tumors, including cervical, but also pancreatic, head and neck, bladder, cervical, endometrial. We wanna be very inclusive in this opportunity, and I think to really show the benefit and expand the benefit of what a tissue factor program can do, and not be restricted just to cervical cancer patients. Yeah. Okay. You're in the clinic. Congratulations on that. That was very quick, right? Since you'd become CEO. We were, you know, kind of waiting. We were surprised actually, pleasantly surprised that you were able to get to the clinic so quickly. As you think about, and you're starting at kind of the top end of your preclinical ceiling, right? In terms of dosing. As you think about this clinical study, how are you thinking about data? When do we see the data? Probably more importantly, how are you thinking about the potential go, no-go decision, you know, based on the data that you see? You mentioned we're moving really fast. I just wanna acknowledge that point because typically when you have a new CEO and you have to restructure a team twice, and then get back in the clinic in six months is not an easy thing to do. The fact that maybe we had a 1% chance of actually doing that, and we hit it as a team, and I'm incredibly proud of the execution of the team. We have this new discipline around execution and validating our science in the clinic. I think again, we're moving really fast on this program. We got the clearance in October. We started this phase I trial for the tissue factor program in November. I've guided to initial top-line data by middle of this year, which is like six-eight months after we start a trial, so we're again moving very expeditiously to data. I think we have to understand that, you know, phase I programs are really meant for safety, you know. We're moving so quickly, it's not likely we'll have a lot of durability at the time that we see the data. Safety is preeminent in the phase I trials, especially given the fact that we have a HNSTD of 50 milligrams per kilogram. Even at those doses, we are not seeing any ocular, skin, or bleeding events. We wanna make sure that we validate that in humans as well, and be able to have a clean profile from a safety perspective. We're also looking to get some PK, as well as some early signs of activity in other tumors as well because it is a basket trial of seven different tumors that express tissue factor. I think for this, you know, it's important for us because this program, you know, the construct is very similar to what we have for STRO-006 and our dual payloads as well, validating this new optimized linker payload system. It'll have a nice read-through into the rest of the pipeline. Excellent. Why don't we talk a little bit about 006 then? This is integrin beta 6 ADC. Yeah. Maybe talk to us, give us an overview of this molecule, and of course, of the target and when do you hope to, you know, be in the clinic for that? I think. Well, I'll ask you the competitor question afterwards. Yeah. STRO-006 is a very high value target. Sometimes, you know, STRO-006 is our middle child. In some ways it gets overlooked because they, most people focus on STRO-004 'cause it's already in the clinic, and then they move quickly to the dual payload ADCs. But STRO-006 is a high value target that it's already been validated in non-small cell lung cancer. There's a Pfizer program that actually showed some initial data around 20%-30% ORR in that second, third line space. And I think some room for improvement on the safety side of things. I think for us, actually recently Pfizer did announce that they are going tripling down on this target. They like the antibody, and we like their antibody as well. We don't love their linker payload system. We believe that this could be a very big clinical and commercial opportunity for us. It is also a DAR 8 exatecan payload system optimized with the beta-glucuronidase linker, further stabilized with our non-naturals in the click chemistry in our sulfonamide system. Okay. When we think about this differentiation, so Pfizer's doubling down, so clearly they like, w hat they're seeing. Yeah. You know, how do you hope outside of safety? Is the differentiation primarily gonna be on the safety side 'cause you do have this high HNSTD, you know, that you're seeing in preclinical models? Do you think that would translate, since it is safer, to potentially staying on drug longer and that having an impact on efficacy as well? Yeah. The STRO-006 program is well tolerated. We're actually seeing doses tolerated at 30 milligrams per kilogram, which is very high. I don't think in achieving safety, we also want to actually drive the anti-tumor activity. Again, the payload is an exatecan payload, which is one of the more potent exatecan forms of payload, and we haven't reduced the DAR. We kept it at DAR 8. We're really trying to drive the anti-tumor activity in addition to driving greater safety. When we think about threading the needle or the development path here, is it a fast follower to what Pfizer's already doing, and you're going into non-small cell? Do you look for other indications completely so there's some more white space? Yeah. How should we think about that? I think STRO-006 is a integrin beta 6 targeting is a more focused development plan, obviously validated in lung cancer, but also expressed in head and neck and esophageal and some other tumors. I think this is, you know, an opportunity for us to showcase the versatility and the strength of our platform going after this target. I think even if we were to share an opportunity in lung cancer, you know, that's a sizable opportunity for us moving forward. I probably asked this, or you may have mentioned it, but I've forgotten. Is it, when do we plan on this being in the clinic? Yes, we're on track for an IND this year and into the clinic, yes. I would say the important safety piece on, for lung cancer, all three of our programs are actually going after lung. And the antibodies that we make in the cell-free system is, again, Fc silent. This avoids. It's one of the mechanisms that has been known to, like, lead to pneumonitis and ILD. The fact that we can actually clearly avoid that will be a potential differentiation for the program. Correct me if I'm wrong, I think, you know, the interstitial lung disease, that's been kind of the death knell for several programs for them to, you know, come out of development, right? To halt development. I think exatecan payload ADCs tend to be associated with ILD and pneumonitis, and it shows up pretty early in terms of the dosing at lower doses as well. This is something that, especially in lung cancer, you don't wanna actually contribute to anything happening in the lung. I think that is something of an advantage if we're able to validate the fact that the Fc silent proves to avoid this in the clinic. Okay. This is just a preclinical sort of question that, you know, as you're doing your preclinical work, do you typically benchmark it against kind of approved therapies, or do you even benchmark it against therapies that are in development? Well, typically in preclinical models, I think this is the case for all companies, that you can benchmark against commercially available products. If some product is in development, you would, you could make a surrogate of that, and we've done that. We've actually done some extensive PDX work where we've gone head-to-head against the surrogate Pfizer model with the vc-MMAE payload, and we're seeing really durable first deep responses, but then durable responses in the sense that the tumor regression, like, lasts 40 days out. Yeah. Okay. Let's switch gears and talk a little bit about something that's quite unique, I feel, like, you know, to Sutro, and that's your dual-payload ADC program. Can you give us an overview of that, and kind of what's the rationale behind that program? Yeah. Dual payloads are exciting. If ADCs are targeted chemotherapy, then dual payloads is targeted chemo combination therapy. We know that chemo combination is more effective than single agent chemotherapy, and we know that resistance now that we're seeing resistance happening with single payload ADCs can be overcome with the dual payload strategy. Again, though, how do you actually thread the needle on safety as you're delivering two potent payloads with an antibody? I think what's exciting for our data in our preclinical work, we've already seen one of our first programs also be dosed very high at 25 milligrams per kilogram. That gives us reason to believe that we can actually deliver on the safety of dual payloads versus even just single payloads. We see that resistance is really driven not by the target, more so by the payload class, as evidenced by the fact that there's lots of HER2 agents right now that patients get treated sequentially with. You don't see degradation of the target. The resistance is driven more by chemotherapy or the payload class, and one way to overcome that is with a dual payload approach. The dual payload comes into the clinic or an IND is expected when? Yeah. We moved up the timeline for our dual payload. It was originally second half of 2027. We moved that up to later this year. That's also very quick for you guys. Another question on the dual payload. You also, you know, have been very good at setting up partnership agreements. I believe, correct me if I'm wrong, the Astellas partnership is also a dual payload, but it's an IO dual payload. If I remember right. Yes. Actually, it'll be one of the first dual payload programs into the clinic. We have an important collaboration with Astellas. It is an immuno-stimulatory agent plus a cytotoxic payload. Astellas, our partners, have just recently announced first patient dosed in their first TROP2 iADC program. That's wonderful. I guess we should be expecting data from that probably in 2027 or how does that work? They're not gonna be as quick as you maybe 'cause it's. Well, they're moving fast. Okay. I can't guide to their program, but I'm excited that they're moving forward with this very differentiated program. Okay. 227. We've been talking about PTK7. Lilly has a program, Whitehawk has a program, Zymeworks announced a program, everyone's on this target now. You know, everyone has seen kind of what's happened with Pfizer and AbbVie and that they've discontinued development. Would love to kinda hear your thoughts about this target, how you plan on differentiating. I think PTK7 is a very exciting target. It is expressed both on stem cells as well as multiple solid tumors. Already there's been some validation of this target with a previous Pfizer-AbbVie program. Again, can be improved from a first-generation payload class of ADC. While several companies are going after this target with a single payload exatecan or Topo 1 payload, we think our program will be very differentiated with a dual payload construct. We're excited that we're able to get to a 25 milligram per kilogram safe dose in terms of safety, and that we're seeing as high as that without severe toxicity. This gives us reason to believe that this can be a very exciting program. Have you commented on when this might enter the clinic or an IND might be filed? Yeah. We, as we just shared, that we have accelerated the timeline into this year. Oh, perfect. For IND submission. Okay. As you think about the clinical development here, right, and when we might see data and what kind of data you would like to see here, it's a little bit more of an open space, right? There's no approved therapy. I'm assuming that you would have to compare yourself to other therapies in development, whether it's the same target or not. How do you guys kinda decide, like, "Hey, this is a good profile that we wanna move this forward? Yeah. I mean, listen, phase I programs typically are more around safety, to confirm safety. The expectations for phase one programs have gotten higher. You're gonna wanna look for signals of activity even at low doses, right? I think, you know, being able to design ADCs where you have a really high ceiling for safety, but also seeing antitumor activity at a very low dose, really that's what we mean about widening the therapeutic window. We've already seen our preclinical work that has kind of been evidence to what PTK7 dual payload program can be. We'll be looking to see that validated in the clinic as well. Got it. Manufacturing, kind of the last 3.5 minutes we have left. Manufacturing was always something that, you know, you guys held very close. You were in charge of it. It was extremely costly. You have three, you know, probably going on four programs now that you want to, you know, bring into the clinic, right? Or one's in the clinic with the others to bring into the clinic. How are you thinking about manufacturing? How do you keep your costs low, as you know, execute your programs? I think, you know, 10 years ago, not a whole lot of CDMOs were making ADCs. When you have a brand-new technology, you sort of have to build it in-house first. Now, if you look outside, there's a lot of CDMOs actually doing ADCs. We have largely externalized our CMC capabilities to larger scale CDMO partners this past year. We had a small manufacturing facility in San Carlos that we have decommissioned, and we've only kept the really specialized parts of our technology, the cell-free upstream antibody work internal, and everything else downstream can actually be externalized. You can actually manage those expenses. With our CMC and cost of goods, I've been part of the Avastin and KEYTRUDA launches. Well, some of our teams have been part of the KEYTRUDA launches. They launched at, like, 1 gram per liter, right, in terms of yield. We're already there at the clinical level. We'll get to commercial level where the yields are much more improved than that, and we have a strategy around getting there in terms of improving the yield for XpressCF as well as our antibody work and just the scale and consolidation of our network, which will also help in doing that. The whole strategy there is to be very competitive to what conventional ADCs cost. Got it. As we think about costs, what's the current cash position at the company? I think you guys did a raise recently with marquee, you know, healthcare investors. Maybe just kinda take us through how long this cash will last. Yeah. Right now, we have cash into Q2 of 2028. It does not include all of our collaboration milestones with our partners, and that could further extend the runway. Importantly, we have the money to validate all of our programs right now in the queue in our pipeline to get to initial proof of concept data, and I think that's really meaningful for us. Great. As we think about, you know, kind of the last minute, we've talked about this, you know, sprinkled throughout our talk, but as we think about the next 6- 12 months, what should investors be kinda focused on? I'd asked this question before, are we seeing more preclinical data? You mentioned the clinical data from the middle of this year, and I think everything else probably goes out to 2027. Can you just lay out for us the next milestones? Yeah. I would say, listen, last year for Sutro was a transformation year, right? We've right-sized the company. We've extended the runway 3x-4x. We've accelerated our programs. 2026 is a pivotal year for us in terms of getting to data for STRO-004, getting into the clinic with two additional programs, multiple opportunities to validate our science and technology. We'll have data for STRO-006 and STRO-227 next year. So we're very excited about the opportunities to really showcase what Sutro can do. Terrific. Jane, thank you very much for coming. Okay. All right. Thank you.