All right. Welcome, everyone, to the last day, day three, Jefferies 2024 London Healthcare Conference. My name is Roger Song, one of the senior analysts covering biotech in the US. It's my great pleasure to introduce our next presenting company, Sutro Biopharma. And now I turn it over to, CEO, Bill Newell. Thank you, Roger. It's a pleasure to be here, and thank you all for attending today's presentation. In the course of my discussion today, I'm going to be making some forward-looking statements, and this is all you need to know about those forward-looking statements. At Sutro, we've been working on next-generation ADCs for over 10 years, and we've been building with intentionality with a goal of creating long-term sustainable value. We're doing that in multiple ways. Right now, we have a very advanced asset in Luvelta, luveltamab tazevibulin. It is in a pivotal registration-directed study for platinum-resistant ovarian cancer, as well as for an ultra-rare form of pediatric leukemia. And there are other indications I'll talk about in the course of today's presentation. But we're more than just Luvelta. We also have an emerging pipeline of next-generation ADCs. I'll preview some of that today as well. Lastly, we've had a strong history of partnerships, and that's been an important part of the company's development because to do new modalities, ADCs, to use a one-of-a-kind platform technology, cell-free protein synthesis, you require a lot of capital. We've been able to access that predominantly from partnerships where the cash received has been almost $1 billion to date, and equity financing, as well as other vehicles for financing. Our pipeline really offers a broad potential for both near and longer-term opportunities. We have a late-stage product in hand, and that late-stage product is one that we believe has multi-indication potential. In fact, we think of this as a pipeline and a product. We're more than that. We also have our next-generation ADCs that are using the latest technologies for linkers and warheads, including an exatecan-class warhead. We are also thinking to the future about dual payloads, something I'll comment on later. Recently, we've committed to three INDs over the next three years, so one in 2025, one in 2026, and one in 2027. The 2025 IND is our STRO-004 tissue factor targeting ADC. It's a DAR8 exatecan, and I will talk more about that in the future. It's important, as you build a company, to be able to maintain adequate capital along the way so that you can pursue all the opportunities that the science affords you. We have a strong history of doing that. We ended the third quarter with almost $400 million in cash, cash equivalents, and marketable securities. As I mentioned, we've raised almost $1 billion in our collaborations and partnerships. Along the way, we've spun out a really leading vaccine company in Vaxcyte. They rely on our technology to make their 31-valent pneumococcal conjugate vaccine and all the other vaccines that they are in development. We sold their royalty for the pneumococcal conjugate franchise to Blackstone for $140 million and $250 million in future milestones. While we don't typically partner assets that are preclinical, we did find a really interesting opportunity to advance STRO-003, which is a ROR1 ADC, in collaboration with Ipsen, and we received almost $100 million in funding from them. We've had a great relationship with Astellas, where we're looking forward to our next-generation type of molecule that is a dual-targeted, dual-mechanistic payload. In this case, it's an immunostimulatory ADC, site-specifically conjugated with both a cytotoxic payload that causes immunogenic cell death, as well as an immune-stimulating agent that's designed to allow for the immune system to do mop-up work in the cancer. Lastly, we have licensed Luvelta in Greater China to our partner, Tasly, and they have been pursuing the clinical development of that in the Chinese patient population. Let's dive deeper into our lead program, Luvelta. Luvelta was deliberately designed to be a differentiated ADC. As we saw what is now the approved ADC initially stumble with their first pivotal trial, we undertook an analysis of what could be wrong with the construct of the molecule and how could we design something different and better. Better in terms of allowing more patient benefit, better in terms of allowing more patients to benefit, and better in the sense of having a less burdensome toxicity profile. In fact, because of the design feature of this asset, we now are able to address the population of platinum-resistant ovarian cancer patients where 8 in 10 women could be benefited from our therapy in contrast to the approved agent, which is on label for 3 in 10, and we've done that through an elegant design of a tubulin inhibitor, high-potency molecule, higher potency than the competitor molecule, a higher bystander effect, and a lower effect as a PGP substrate, meaning when we get the antibody-drug conjugate into the tumor, it is less likely to be pulled out. Based on the data we've generated today, we know that fully 8 in 10 women can benefit from treatment with luveltamab tazevibulin compared to 3 in 10 women who are on label for the competitor molecule. In addition to ovarian cancer, though, we've studied our ADC in endometrial cancer, and we've started a non-small cell lung cancer trial. I'll talk a little bit more about that, as well as the ultra-rare form of pediatric AML, the CBF-GLIS2 mutation. It is ultra-rare, but there's a strategic reason for us pursuing it that I will get into shortly. Importantly, when you're the second folate receptor alpha molecule that is seeking approval, you want to find a niche that you can really own yourself. And the niche is the opportunity to be the first to market in the medium and low patient population. So what you see in the green box and the blue-green shaded area is the population we are intending for our label. It is eight in 10 women with platinum-resistant ovarian cancer. The overlap is only in the small blue and green hatch section where Elahere is indicated on label. And so we think we have a tremendous opportunity to more than double the addressable patient population. Through the course of many years of clinical development, we've had a chance to study Luvelta in over 100 patients. This really nice plot really demonstrates that regardless of the dose level, because these are all the efficacious doses that we've studied, you see substantial disease control in the process of developing this molecule. We're going to drill down, and I'll talk about what our go-forward dose is soon. We're going to drill down and have the optimized dose that is the subject of the registration study. But even doses that are not clearly the optimized dose still induce tumor control, which is an important hallmark in terms of driving patient benefit. One of the things that I'm pleased about the design of our molecule is that we do not have the ocular toxicity or lung toxicity profiles that other potential agents for platinum-resistant ovarian cancer have demonstrated. The safety indication that we have to pay attention to is neutropenia. It's important to bear in mind that virtually all the women who are in our patient population are neutropenic or have been neutropenic from the prior therapies that they've received. So neutropenia is a well-understood side effect profile for the treatment of women with platinum-resistant ovarian cancer. Physicians manage it all through the course of the disease, and they're used to managing it now with Luvelta. But that did take a little while. When we saw a risk of high-grade neutropenia, importantly, not febrile neutropenia, but grade 3 or grade 4, when we saw that risk, we thought about, particularly at the higher dose, 5.2 mg/kg as a starting dose, how do we ameliorate that? And we spent a lot of time understanding the onset of the neutropenia. It's not as immediate as you often find with chemotherapy. It's more of a delayed onset. And so we thought about when would be the optimal time to intervene with G-CSF. And through some work that we did and discussions we had with the maker of G-CSF, we came to conclude that if we dosed G-CSF on day eight after administration of luvelta, we would have the optimal benefit of dampening down the risk of high-grade neutropenia. We studied about a year ago a small cohort of patients and demonstrated, as you see in this graph, that we can fully reduce the risk of high-grade neutropenia by 90% in cycle one and by almost 75% in cycle two. So we thought we've got now a way to control and avoid the risk of high-grade neutropenia, as I said, the major safety signal that we were looking for, and we're able to maintain good patient benefit in terms of disease control. So where are we in the development of this molecule? As a result of Project Optimus, we have a two-phase pivotal trial. phase one, or part one, sorry, I should say part one, is about 50 patients where we agreed with FDA we would study the top dose, 5.2 mg/kg, four to two cycles with prophylactic G-CSF on day eight, and then dropping down to 4.3 and compare it to 4.3 mg/kg for those patients. Of course, physicians have discretion to use G-CSF during the course of treatment of their patients as they or their institutions deem appropriate. Part one was completed in terms of patient enrollment in April of this year, and we were able to move on to part two. We did not have to hold the trial until the optimized dose was selected and approved with FDA. So at present, we are enrolling two different dose cohorts for Luvelta, as well as a chemotherapy control arm that allows us to really start that pivotal trial early, in fact, in the May timeframe of this year. We have about 516 patients that are going to be needed for the approval process to gain full approval of this molecule, and that is well underway at this point in time. We have the data from part one in hand. We believe we understand what the optimized dose is going to be. We are on track to have discussions with FDA about that optimized dose and secure their agreement that that is the right dose. Then be in a position, we hope, if FDA doesn't believe this will interfere with trial integrity for the remaining and ongoing pivotal portion of the trial, we'd like to talk about what that optimized dose has shown and why we're carrying it forward in this phase three pivotal trial. When we've met with FDA, we will drop the other dose, the non-optimized dose. Those patients will only be followed for additional safety purposes. Stay tuned. We'll have more later this year, early next, on how Luvelta is moving forward for platinum-resistant ovarian cancer. I mentioned also that we had started a pivotal trial in an ultra-rare form of pediatric leukemia. This came about in a rather unusual way. We got a request from an investigator at Fred Hutch, Dr. Soheil Meshinchi, for some Luvelta to use in preclinical models. This is an ultra-rare form of leukemia. It probably affects less than 100 children a year. He had been looking for active drugs with targets that are overexpressed, even a bit overexpressed, doesn't have to be wildly overexpressed in this form of leukemia. It turns out folate receptor alpha is overexpressed, and he got several different molecules that target folate receptor alpha. Ours was the only one that actually succeeded in preclinical models in eliminating the disease in mice. That data was shown at ASH in 2021. Subsequently, we started receiving requests for compassionate use single-patient INDs in this ultra-rare indication. Of course, because the target was expressed, we felt it was our obligation to be able to meet these patients' needs. To date, I'm pleased to say we've treated over 40 patients on a compassionate use basis. We thought, okay, there is something there. The data has been previously presented at ASH as to how these patients on a single-patient IND basis have been done. I'll touch on it briefly here in today's presentation. But the fact of the matter is we think there is a path forward to get this registered. We need about 20 of these infants and toddlers. It's a highly aggressive disease. We are taking the most refractory patients. They have either not been able to get to stem cell transplant because the chemotherapy induction regimen did not work for them, or they have relapsed after stem cell transplant, and they have substantial blasts in their bone marrow, making it a very difficult patient population, but one in which we've seen benefit through the compassionate use program, and you'll see some data on that. We'll need about 20 patients in order to register this molecule, this medicine in that patient population. We have the opportunity for a pediatric priority review voucher. There's some regulatory advantages for that, and so we think, and some commercial preparatory work that can be done, and so we think it's worthwhile and relatively inexpensive to pursue this as another pivotal trial at this point in time. As we think about the future, though, of treating patients with ovarian cancer, we know that platinum-resistant ovarian cancer is the very end of the road for many of these patients, but that's where you start in the development of a new cancer medicine. What we've also done, though, is tried to think about where is the future of Luvelta and how does it fit in the treatment regimen for these women on a going-forward basis. We think, good as the molecule has demonstrated its efficacy as well as its tolerability in late-stage ovarian cancer, there's a path forward to move it earlier lines of therapy using a combination approach, predominantly with bevacizumab, which is used in earlier lines of therapy. Here's some work we presented at ESMO earlier this year. If you look at the 4.3 mg/kg dose, we had fully a 55% response rate in the combination. If you look at those patients who are limited in terms of they've got an expression at the high TPS equal to or greater than 25%, that's the patient population we're studying as a single agent. You see a 44% response rate. Interestingly, even in patients where the target is expressed less than 25%, we still have an almost 30% response rate in combination with bevacizumab. Importantly, even in bevacizumab pretreated patients who you might think would not have much in the way of a response, we had a 22% response rate. Really impressive. We're continuing to add more patients to this group, and we'll look to report more on the combination data next year. As I said, we've studied this molecule in endometrial cancer where we saw a robust 29% response rate in the TPS greater than 25% group. These are the curves in the children, the infants and toddlers who've been treated on a compassionate use basis, the first 25. This is some very exciting PDX data in non-small cell lung cancer. That trial is open for enrollment, and we look forward to talking about the data, at least the initial data in that phase two trial, sometime next year. Lastly, we know from this waterfall slide or this colorful slide, let me put it that way, that there are many cancers in which folate receptor alpha is upregulated, some to a greater extent, like ovarian cancer, some to a lesser extent. Because we're able to benefit even patients in the lower expressing tumor groups, we think this has an opportunity to be explored and benefit a wide range of cancers well beyond what we've already talked about. Now, as I said, Luvelta is not the only thing that Sutro is about. We're working to deliver three INDs over the next three years. And what we're really focused on is making sure that we're advancing and enhancing ADCs both inside and outside the tumor. About 1% of the ADC actually makes it to the tumor cell, and that's responsible for the patient benefit that you see. You have to worry about the 99% that is not making it to the tumor cell and what that does outside the tumor, creating toxicity that is not beneficial to the patient. We held a research forum in October where we talked about our strategies for addressing both inside and outside the tumor. I'll share a snippet of this, but I do encourage you to go back to our website and find the research forum slides and the presentations that we made. It's very informative because you actually can now predict what the toxicity profile outside the tumor is going to look like. You can actually have animal models that allow you to actually demonstrate that your molecule avoids those toxicities, or if it doesn't, you tune the molecule again to improve it so it avoids those toxicities. And then we have strategies to improve the performance of the ADC inside the tumor. One of the things that everybody's excited about are the new topoisomerase ADCs, and we're excited about them too, but we're going to go beyond them. So when we profile our platform and what we're able to do with topoisomerases, can we get to DAR8? Yes, we can. Can we do a beta-glucuronidase linker, which is the next generation more stable linker? Yes, we can. Not everybody can. Can we do dual payloads? Yes, we can. Not everybody can. Are we able to add immunostimulatory agents? Yes, we can. Are we able to do site-specific conjugation, keep the FC receptor silent, do a bispecific format, and do this all in a high-throughput format? Our platform is the only one of the platforms listed here, and these are a lot of names you'll know, that is able to achieve all of these. So how are we applying these? Our next generation ADC that's going into the clinic next year is our tissue factor ADC. It's a DAR8 exatecan site-specific. We have clinical validation from a molecule that tells us that tissue factor is a really exciting molecule, particularly for women with cervical cancer, but we see early signs of activity and potential in other cancers, head and neck, pancreatic, and other multiple solid tumors. We'll talk next year more about what our clinical design strategy is, but we use an exatecan because it's a clinically validated payload. It has potent activity and a bystander effect and reduced susceptibility to resistance. The beta-glucuronidase linker is a superior linker that allows for enhanced tumor selectivity and addresses hydrophobicity concerns. We have a high DAR, and we have an optimized conjugation. As a result, we have an impressive safety window where we're able to dose up to 50 mg/kg in non-human primates and avoid the typical toxicities, including ocular toxicity that you see with other tissue factor targeting agents. Here's some data of a few of the PDX models that we have done. We wanted to validate that we were actually on the right track with an exatecan versus the approved agent. We also wanted to validate that a DAR8 molecule would have better disease control preclinically, and therefore we believe clinically as well, because we're able to increase the exposure with a DAR8 over a DAR4 molecule. By being able to increase the exposure, you're able to improve the efficacy potential. And we have, as I said, a very favorable side effect profile. In fact, we're able to widen the therapeutic window dramatically compared to the approved agent, as this slide demonstrates. And enhanced exposure does lead to improved efficacy. So we're excited to get this molecule into the clinic. Our R&D focus is also about making ADCs better inside the tumor. I alluded to that before. So we have multiple different dual payload ADCs, and we're looking to ways in which we overcome resistance. One thing we know is that if you're resistant to topoisomerase, when you develop that resistance, the second topoisomerase will be less effective in terms of patient benefit. But another mechanism, another killing mechanism, like a tubulin inhibitor, of which we have tremendous experience with, that can actually be a beneficial follow-on molecule in terms of patient control. Now, we thought about dual payloads, and do they actually add patient benefit? And based on the models that we have here and talk about more in the research forum, you see that a topoisomerase inhibitor and an anti-tubulin agent across the board result in better cell kill. You also see another construct, another idea we have for dual payloads, which is a topoisomerase and a PARP inhibitor. And you can see the results here. Again, two is better than one. Lastly, in our collaboration with Astellas, we're working on immunostimulatory agents where you add in a very site-specific manner at specific ratios that are relevant to the tumor and the tumor microenvironment, an opportunity to synergize between the cytotoxic payload, which causes immunogenic cell death, and really signaling to the immune system that we want it with an immunostimulatory agent, that we want the innate and adaptive immunity mechanisms to come together. And so as we thought about the design of these molecules, again, we looked at what are we doing with our IADCs versus the other modalities that are known as immune stimulatory approaches. And in fact, we have a distinct advantage over all of them, as this slide demonstrates. One thing that people along the way have asked us is, do we have the ability to scale this novel cell-free technology to a commercial scale? We've been working on cell-free since the company was founded in 2003, over 20 years ago. Over the last two to three years, we've made dramatic progress in terms of our evolution of CMC. In fact, we've enabled the production of an antibody intermediate STRO-004 at the 4,000-liter scale under GMP conditions. That is the world's first large-scale cell-free production ever achieved, and that's the scale that we need both for the pivotal trial and for commercial scale. So we have conquered the commercial scale challenges and are aggressively moving forward with this molecule. So as I said, Sutro is more than just Luvelta, although we're very, very excited about the potential for Luvelta and look forward to the pivotal data. This is a look at our whole pipeline, and I want you to know that we are building both for the near term and for the long term. We have a very experienced leadership team. Most recently, we added Hans-Peter Gerber, our Chief Scientific Officer, who's leading our next generation ADC work. 25 years in ADCs, starting at Genentech, Seagen, Pfizer, and many other companies. He's one of the godfathers of ADCs, and we're delighted to have him working as a member of our team. So that's what Sutro is about. Thank you so much for being here today and attending our presentation.