... All right, everyone, I think we'll get started here with the next fireside. My name is Derek Archilla. I'm one of the senior biotech analysts here at Wells. I'm very excited to have Sutro Biopharma here. From the company, we have Jane Chung as the CEO, and as well as Greg Chow, CFO. Thank you guys for joining us, and looking forward to the discussion here. Yeah. Thanks, Derek. Thanks. So maybe, Jane, you wanna just kind of give us, you know, a quick background? A lot has changed with Sutro. We were just talking about that, you know, over the last 12 months and, you know, repositioning the company. But maybe you can just kind of talk about the overall strategy and what's happened, and then we can start with the Q&A. Yeah. So thanks for the opportunity to share the transformation story for Sutro. I think, you know, it's really not an easy time for a company to pivot from a Phase 3 asset into an early-stage clinical pipeline. But we have made considerable advances with the technology to really differentiate our early pipeline, and we think that this will drive the most value for shareholders and actually be better for patients. So it's not an easy decision in these times, but it is a brave one, and hopefully, as we move into the clinic and can validate our early programs, we'll soon get credit for them. Yeah. Perfect. Yeah. Maybe let's talk about, you know, STRO-004 and, like, you know, how you view this based on what we know today preclinically as kind of differentiated relative to the other landscape for tissue factor ADCs. Yeah. Before jumping into STRO-004, if I could just- Sure ... highlight what is really unique about Sutro's platform. And I think the uniqueness happens because of the far greater design capabilities of optimizing every component of an ADC. An ADC has multiple pieces to it, and so it's not easy to, like, kind of figure out the game plan here. But to be able to optimize every single component, we've upgraded our payload platform to an exatecan-based platform. We've even gone as high DAR as 16 without actually compromising the PK. We've improved our linker strategy with our beta-glucuronidase linker, which is further stabilized with our non-naturals in the cell-free click chemistry. And we've also... Our antibodies are expressed and made in a cell-free extract, E. coli extract, which is Fc silent. Many of the ADC companies are looking to avoid the glycosylation and the engagement on the Fc gamma receptors that are located on normal tissues to avoid those unwanted side effects and liability. So I think, you know, we're fundamentally changing the way these medicines are made, not to make me-too medicines, but to really transform the standard of care, first with our single-payload ADCs that are going after hard-to-reach targets to ensure our commercial viability moving forward, and then with really excited about the dual payload strategy we have, that is very not as easy to do with conventional ADC technologies and be able to combine different modalities of payloads to be able to overcome resistance and then potentially compete against single-payload ADCs to be best-in-class performance ADCs. So getting to STRO-004, we've made a lot of improvements on the design, including upgrading the exatecan payload platform. We also have improved the beta-glucuronidase linker strategy there as well. We've incorporated that, and our antibodies are Fc silent again, so we don't engage with the Fc gamma receptors that avoid the toxicities associated in ocular, the skin, as well as even bleeding risk. Gotcha. And maybe just, can you, like, as you go through each of the different, you know, parts of the ADC, like why exatecan and, like, why you think that is, you know, the right move? And then also in terms of, like, the linker strategy, you know, how are you really differentiated versus kind of what's out there? Yeah, so I think the field has seen that the exatecan payloads have really disrupted the ADC field and really leveled up the performance of these payloads, and we have also incorporated those payloads into our ADC design. That said, we're gonna take a step further and actually do multiple payloads in the future, which will actually have the ability to overcome resistance to single-payload ADCs, and that could be really game-changing for the field of ADCs in the future. It's important to improve the linker design as well, and that's where we've optimized this beta-glucuronidase linker. This hasn't been a relatively new linker strategy, but we have modified it with our proprietary protein engineering to be further stabilized with the non-naturals in our cell-free system. That's better cleaved inside the tumor as opposed to outside the tumor, again, affording a more safe profile for the product. Gotcha. Okay. So maybe just, you know, can you highlight some of the preclinical data that you've generated? Obviously, you know, Tivdak out there and also there's competing, you know, tissue factor ADCs. So, like, you know, how are you kind of stacking up head-to-head? And, you know, ultimately, as you enter into the clinic, you know, what should we be thinking about in terms of, like, you know, how that, you know, initial trial should go? Yeah. So with our tissue factor program for STRO-004, we have seen a 50-fold increase in exposure with an HNSTD of 50 mg per kg, which is the highest dose we've seen in NHP models. That's very significant. If you compare that to the approved tissue factor program at 3 mg per kg of an HNSTD, you see a marked difference between the two, and it's important that we actually dial up the exposure to be able, in a safe manner, so that we can actually increase the dose. And then on top of that, we actually have looked at the activity of STRO-004 with our DAR8 exatecan, and we've actually made two versions. We made a DAR4 exatecan and a DAR8. And the DAR8 exatecan version actually outperformed the DAR4 version in terms of driving activity broader than cervical. So we really want with STRO-004 to redefine the tissue factor opportunity. We see a significant clinical opportunity to address unmet needs in multiple tumors that express tissue factor. Gotcha. So as you think about what tumor types, I mean, obviously, you know, we've got Tivdak as kind of the initial, but, like, do you think is it just fast follower, you know, kind of strategy, or you, because of the profile, you can broaden out to new tumor types? And what tumor types would those be? Yes. Again, we see this as an opportunity to redefine the tissue factor program well beyond cervical- Mm. Cancer. So, seeing activity in the preclinical models with STRO-004 at doses of as low as 1 mg per kilogram, and so this is really something that is striking and significant for us. I think it would be easy to show POC, or proof of concept, in a cervical tumor, but at the same time, we want to make sure that we drive activity well beyond cervical, including tumors like lung, head and neck, pancreatic, esophageal, which we've seen in our early preclinical models. Gotcha. And also, like, how are you thinking about, you know, going forward with dosing strategy? Like, obviously, you know, you gotta do the, you know, kind of step up in dosing and really kind of hone in on the dose, but, like, it seems like you've got a lot more flexibility. So yeah, like, does that speed things up once you've entered the clinic, or how are you thinking about that? Exactly how we're thinking about it, Derek. Okay, that's... I'm just asking. Yeah, so you're leading the witness. I would say, given the higher exposure and the higher HNSTD of 50 mg per kg, we definitely wanna be conservative enough since this is our first program in the clinic on this platform, but at the same time, you know, be very thoughtful on how to get to an effective dose and data as quickly as possible. Makes sense. Okay, so I guess in terms of, like, what you need to do from today to then, like, what sort of execution and what steps? Like, are there gating factors? What do you actually need to get done here? Yeah, we're on track. We're on track with the IND in the second half of this year. Not easy to do when you've pivoted the company- Sure ... in March, six months ago, and we'll be back into the clinic with first patient in and first sites, activated, this year. I mean, are you pretty much done all, like, the preclinical tox work or, like, you know, more just filing? Okay. Yes, it's all the packages to come down, come together, but all in the filing and last remaining steps. Gotcha. Well, like, when you think about Tivdak, was a lot of that ocular tox and some of the toxicity, was that already known in the GLP tox, like animal studies, or was that... I'm just kind of curious, like if you're doing any additional testing to understand whether you actually have any of these signals? Great question, 'cause I forgot to mention that, you know, with tissue factor, it is a target that is expressed in normal tissue as well as in cancer cells. And it has been seen with the approved program that there is ocular tox, skin tox, and bleeding events or bleeding risk. Despite the higher exposure we're driving with the HNSTD as high as 50 mg per kg, we're not seeing those liabilities with our program as well, which clearly shows the differentiation for the STRO-004 program. Gotcha. And as you guys kind of have pivoted and maybe reinvented yourself, how do you guys think about disclosure in the future in terms of, like, Phase 1? Like, is this something that you'll kind of dribs and drabs some cohorts? Will you wait for medical meetings or, you know, how much of a robust data set do you want to have before you actually share, you know, kind of some of the early data? Yeah. Our ambition is to get to data as quickly as possible and be open to sharing interim top-line results as soon as possible. Gotcha, so maybe we can, you know, shift gears, unless there's anything else on STRO-004, but for STRO-006, in terms of like, you know, other kind of programs that you have. Like, again, where do you think the differentiation is gonna be, and ultimately, like, again, going forward, just how do you utilize the platform- Yeah ... here at Sutro? So before moving on from STRO-004, I would think that first I wanna make the case that, you know, it's an important target, and it's an important program to show validation for both safety and efficacy for the tissue factor opportunity. That being said, the safety element side of the story for us is also a read-through into the dual payloads, right? So the validation of the DAR8 exatecan on our platform, with both STRO-004 and STRO-006, upon which we can add and combine multiple other payloads to it in a safe way, to also drive efficacy in tumor-resistant models, that is actually a very important point as well. Okay. Yeah, yeah. Gotcha. So I guess, yeah, maybe on STRO-006, maybe you wanna highlight that program a little bit in terms of, like, what you're doing there and kind of the- Yeah ... competitive landscape. Yeah. Historically, the integrin beta-6, which is our STRO-006 program, is an integrin beta-6, DAR 8 exatecan with site-specific conjugation of our beta-glucuronidase linker. That is a difficult target to make, Mm-hmm. Because it's really in the proximity of the integrin family of targets, and so there's the normal biological processes of integrin beta family that you don't want to interfere with. At the same time, it is a validated target that has been seen in lung cancer, and so it's quite a substantial opportunity for us, and we have designed a molecule, a product that actually is very specific for this alpha V beta-6 specificity of the target that is driven in the cancer tumor process, and so the specificity allows us to be very mindful of the safety profile, and be able to provide a valuable proposition with this product. I think in terms of competition, because it is a hard target to make, the only significant competitor we see is Pfizer. They have a VC-MMAE DAR4 program in the clinic. It is in Phase 3. They have seen some validation in non-small cell lung cancer. They recently actually are pursuing another program with a DAR8 exatecan as well, so they seem very bullish about the target, as we are. And so, even if we were to share the lung cancer opportunity, which is quite large, it would be a very worthwhile opportunity for us. I mean, is the goal, you know, for either of yous to partner, or is this something that you wanna do solo? I mean, obviously, small company reset, so, you know, in terms of, like, resourcing, you know, where, where do you wanna pick your spot? Yeah, it's a great question. I mean, we have to be flexible for- Mm-hmm ... all types of BD opportunities moving forward. You know, it's also not very valuable to kind of out-license everything- Yeah ... from Sutro as well, so we wanna hold some value for the company in these programs, but we're open- Mm ... to those discussions. I mean, you guys have historically been open to, like, collaborations and stuff, so. Yeah ... I guess, like, now, as you guys push forward with some of these, you know, multi-payload, you know, type of, you know, programs, I mean, is this something that has more caught the eye of potential collaborators? Or, like, you know, what's kind of going on on that front? And obviously, like, again, that's always been kind of a source of, you know, kind of non-dilutive capital, so curious, like, if that's still how you see it and if that's still, you know, something that's achievable. We still see it that way. Okay. We've been historically very successful on the BD front, given the powerful nature of our technology, to making a lot of different things with our, with different therapeutic areas, with the medicines we make. So, you know, I think, for us, we could be one of the first companies in the clinic with a dual payload ADC. That is something that we're very excited about. We have a really important collaboration ongoing with Astellas that has this dual payload with an iADC program, combining an immunostimulatory agent as well as a cytotoxic payload. And so I think we will continue to be flexible in terms of BD opportunities to bring in non-dilutive cash, more to extend the runway, so that we can get to meaningful data on all of our programs. Gotcha. I mean, do you see, like, lung as being the most, you know, or the biggest opportunity for 006, or, or where, where else do you think that could go? Yeah, we've benchmarked our STRO-006 program against the Pfizer VC-MMAE program in lung, head and neck, and bladder, that have variable expressions of integrin beta-6, and we see quite strong activity with our program, so lots of opportunities here for solid tumor, pan-tumor targeting. Gotcha. Yeah. I mean, what else beyond these programs, or what else should we be kind of focused on for you guys, you know, in terms of, again, whether it be, you know, new things coming from the pipeline, or are you kind of got enough to chew on for now? Mm-hmm. Like, what should we be expecting? I think the advancing of the dual payloads is really gonna be exciting for the field. Yeah. We see the dual payloads as the next wave of innovation for ADCs, to overcome the resistance of single payload ADCs, but also compete as a best-in-class potential head-to-head with single payload ADCs. Recently, we benchmarked our dosing strategy or our safety profile when looking at all of the VC-MMAE compounds or products. They actually have an HNSTD, an average of 3 mg to 6 mg per kg. That said, we can add an with our VC... With our MMAE platform plus another eight DAR exatecans, we're getting to 12.5 mg per kg, which is double that of what you'd see with just a MMAE platform. The rate limiting step with dual payloads is the safety and whether you can dial up the exposure in a safe way, and for us to actually double up the HNSTD or the tolerated dose is still increasing or escalating, so that will be a really important element for the dual payload strategy. Gotcha. Yeah. And then just kind of, you know, high-level, broad question on just ADCs in general. Like, I guess this space is quite hot, you know, it's continuing to evolve, you know, dual payload, multi-payload. It's like, you know, where do you think we are in, like, five or so years? Obviously, you guys hopefully be maybe on the market with the first dual payload. Mm-hmm. But, you know, again, how does this continue to evolve, and, you know, what else, you know, are you guys capable of in-house? But also, like, you know, what are you seeing in some of the other, you know, maybe different platforms that are out there that are emerging from, you know, not only in the U.S., but China and elsewhere? Yeah, so I think we see the window of single payload ADCs coming from China, like, closing at some point. Mm-hmm. You know, every deal that's happening on an exatecan platform, the drivers of resistance are really driven by the class of payloads. And so what's next? And this is where we think the dual payloads really have an opportunity. We're seeing some emerging data where, in our tumor-resistant models, where tumors have actually been treated, progressed, and now resistant to a topo payload, then treated with a MTI or a microtubule payload, and then progressed, now see responsiveness and re- and sensitivity to a dual payload ADC. Mm. So, how do you overcome that resistance and then be able to supercharge these ADCs to really have a best-in-class profile? ADCs in general, like, are targeted delivery of single-agent chemo. We see the dual payloads as the targeted delivery of chemo combination. We know that chemo combinations are more effective than single-agent chemo, and how do you deliver that in a targeted and safe way? This is a very unique proposition that really reflects the power of the Sutro technology. It's not just about combining two different modalities, it's about combining it in a way, in different ratios, whether it's one to one, one to two, one to four, that is not the same level of each payload that gets to the right therapeutic window. Gotcha. Yeah. Okay. And then, you know, just in the question around, like, you know, kind of funding, you know, so I don't know if Greg wants to chime in. But, like, just in terms of runway, what do you need, you know, from a cash perspective, to go through kinda, like, the full Phase 1 for both, you know, STRO-004 and STRO-006? I mean, are you fully funded there to data, or would you need to kind of figure out another non-dilutive option? Yeah, no, we're fully funded. We've guided that we're gonna do three INDs in three years. So we think we're fully funded for those three INDs. Okay. We're not fully funded for the two full Phase 1's for STRO-004 and STRO-006. We've guided that we have cash into early 2027. That does not include any of the milestones that we would anticipate getting from our collaboration with Astellas. That would extend the runway, but we're also looking at other ways to, you know, operating efficiencies that we can implement down the road. Okay. Yeah, do we expect any, like, are there any dates or milestones that we should be getting from Astellas or anything that's on the horizon there? We're expecting to get some milestone payments in the next nine to 12 months. Great. And maybe just lastly, in terms of, like, kind of next things, like the milestones over the next six to nine months, where would you, you know, think that, you know, the story is underappreciated? You know, maybe among investors and obviously, again, kind of a reset here, but very interesting platform. But, you know, where do you think that will kind of really start to, you know, speak to investors in terms of like, "Oh, hey, we know we've got something here. This is differentiated." You know, is that sometime this year, or is it more of a 2026 story? I think we'll... That's going to evolve over time. I think for us, we're gonna get back into the clinic, right? So it's not, you know, when you pivot, and then six months later, you're back into the clinic, you can validate your first program. That will have a lot of value for us moving forward. So I think getting back there, being able to, We'll have an R&D day later this year, where we'll be able to share more specifics, and commit to different timelines, more timelines, on how we're accelerating our programs. What's gonna be the big focus at R&D Day? Yeah. I think a lot of focus will be on the tissue factor program- Okay. -right? Back in the clinic. They wanna see the whole dosing strategy and sort of where we're gonna go in terms of the different tumor types and how we're going to develop this program. Got it. Yeah. All right. Well, I'll leave it there. Okay. Thank you so much for coming, and, really appreciate it. Okay. Thank you. Thank you very much. Thanks, Derek.