Excellent. Well, good afternoon, everyone, and welcome to the JMP Hematology and Oncology Summit. It's my absolute pleasure to welcome Sutro Biopharma as the next presenting company, and Jane Chung, President and COO, joining us. Thank you, Jane, for giving us some time today. I never exactly know who exactly is listening into these webcasts, and so I always ask, just as the starting question, for those who are unfamiliar with Sutro, if you could maybe just take two to four minutes giving us an overview of the company.
Sure. Thanks. First of all, thanks, Reni, for having us here. And pleasure to be here with everyone. Sutro is an oncology company focused on ADCs. We have a unique cell-free technology where we fundamentally are changing the way these medicines are made in an E. coli extract instead of CHO-based systems in order for us to incorporate specific design of antibody, linker, and warheads in exact configurations to improve the therapeutic window of these medicines for patients. Our lead program, as you see here, is luveltamab tazevibulin, or luvelta, for short, which is a DAR4 hemiasterlin payload ADC, which is in two registrational trials, one in platinum-resistant ovarian cancer and the other in pediatric leukemia. And also, we're in a phase II trial in lung cancer as well, and have already seen clinical activity in endometrial cancer.
Our next program is STRO-004, a tissue factor DAR8 exatecan ADC, which will go into the clinic next year. Our next programs we highlighted at our recent research forum in October will be DAR8 or higher exatecan ADCs, as well as dual payload ADCs, which very few companies can make that incorporate two different cytotoxic payloads in one product, and can make bold targets new again, as they can potentially overcome resistance to single payload ADCs. We also have very important collaborations as part of our business. Vaxcyte is a spinout of Sutro, focusing on the pneumococcal vaccines enabled by our unique cell-free technology. We partnered with Ipsen on our ROR1 DAR8 exatecan ADC as well, which will go into the clinic next year.
We have an important collaboration with Astellas on a dual payload iADC, which is a form of a dual payload ADC, which incorporates two different payloads, one of them being an immune modulating agent.
Excellent. Thank you very much for that. Let's dive right into luvelta. You have this registrational study ongoing. You have already decided to move forward to kind of the next phase. I guess maybe just give us an overview of the ongoing REFRaME study. Can you give us a sense as to how enrollment might be going, or can you give us a sense that there's already an approved therapy out there, ImmunoGen's drug that's out there? How might that, but how might that be impacting enrollment? Just any sort of an update on REFRaME.
Yeah. So to set the stage and the context for the REFRaME -01 trial, it is really intended to reframe the definition of positivity and expand the eligibility for platinum-resistant ovarian cancer patients for an FR alpha ADC. We've studied luvelta in over 100 patients with ovarian cancer already, as you see from this waterfall plot, showing only those patients that would be eligible based on the inclusion criteria of the REFRaME- 01 trial. Our phase III trial enrollment is well underway, and we've been very pleased to find that we're continuing to enroll patients globally at all levels of expression, including those that are eligible for Elahere, despite their approval. We're on track to finalize the dose with the FDA around the end of the year.
We would also love to be in a position to share top-line data from the part one publicly once we receive the FDA's blessing that it's OK to do that. Upon further regulatory feedback, we'll dictate sort of our decision on what information from part one of a registrational trial will be shared and when we can share it.
Got it. OK. Do you think that as part of that next update, right, because we get asked this all the time, when do we think enrollment for the entire study might complete? If there's any data from part one that you might disclose, we get all those kinds of questions. Is that something that we can expect from the next update? Or really, you would not expect that until maybe all the sites are up and running before you can come in?
Yeah. We look forward to sharing top-line data on the part one if we can. Obviously, the trial is still ongoing, and so we don't want to jeopardize the trial integrity. But I think the initial part one is really designed to be an analysis of the exposure response of these two different doses. And we'll be able to share not only the exposure response analysis, potentially, as well as top-line data. We'll likely want to reserve sort of the robust complete data set for a medical conference in the future. But as long as the FDA is OK with us sharing, we'll be able to share that information.
Excellent. Some of the data we see here, obviously, from the phase I/II study, I don't know, as of the last update, whether or not there were still patients that were on the study or not. Can you give us a sense? Are we expecting any further updates from that phase I/II study? Can you remind us kind of the key endpoints or key data points that increase your confidence in the ongoing REFRaME- 01 study?
Yeah. So we already shared positive results from the phase I/II study at ASCO last year, as well as part of our Luvelta Forum back in January of 2024. And in that data set, we showed robust data of efficacy in both the high patients that were eligible for Elahere, but also in the lower and medium FR alpha expressing patients as well. And I think that really is the differentiation for what luvelta can do to further expand the opportunity for patients to be eligible for an FR alpha ADC. The next meaningful data set that we will have is from the 50 patients in this part one REFRaME- 01 registrational study.
Again, as I mentioned earlier, it is really a dose optimization study where we're looking at the exposure response analysis and assessing the difference between these two doses, the 4.3 mg and the 5.2 mg per kilogram. The data will be a bit of a snapshot here of efficacy and safety and in the broader patient population with a TPS greater than 25%. Following agreement with the FDA on our go-forward strategy and the dose, we look forward to sharing that top-line data.
Got it. It's an increasingly complex competitive landscape. I think you guys have nicely threaded the needle with kind of expanding the market opportunity, especially for those patients that have less folate receptor alpha expression. Can you maybe, I don't know, just give us an overview as to how you're viewing the therapeutic landscape as it matures? I think we got some new data from Genmab at ESMO, kind of how you're factoring in that data versus the Elahere data, right, that led to the approval and the ultimate acquisition of the company.
Yeah. I mean, not surprised to see new competitors, given the target for FR alpha is a validated target, right? So there's excitement on developing new therapies for this target. As we are always closely monitoring all the competitive landscape in ovarian cancer, one thing that's recently come to understand is really the opportunity to sort of sequence these payloads. Most of these ADCs either have a tubulin inhibitor or a topoisomerase I inhibitor payload. And we have seen a lot of recent evidence that these payloads do not have cross-resistance. And so while the Genmab data that uses a topoisomerase I ADC, the data is still early. And most of the data is primarily in China. So we'll see how the data evolves.
But I think there's an opportunity to sequence with these ADCs regardless so that patients get the benefit and the maximum outcome by having more options in this setting. And then we still are well ahead in terms of a phase III trial right now for luvelta. And we feel like we still believe that we have both the first and best-in-class opportunity for the lower and medium expressors and to, again, expand the opportunity to eight out of 10 women who could benefit from an FR alpha ADC.
In terms of, again, just sticking with the therapeutic landscape for a second, and more specifically to Elahere, right, because for all the reasons you just mentioned, we'll have to wait for the data to mature in terms of the Genmab asset. Is it primarily a differentiation between low and medium, call it expression, where luvelta can target? Or are there other features that you've also highlighted that you think could ultimately help create a best-in-class, while not a first-to-market, a best-to-market?
Yeah. Yeah. Thanks for that question, Reni, because I forgot to mention, importantly so, that also the safety is quite differentiating for luvelta, right? We don't see the ocular events. It's very unlikely for us to get a black box warning on a pneumonitis. We don't see the pneumonitis or ILD with luvelta as well. And so in addition, the safety profile, in addition to the fact that you're able to benefit a broader patient population and in the lows and mediums, which currently are still served only by chemotherapy, is a big value proposition for luvelta.
Got it. You did mention, when we were talking about the overview of the company, the fact that luvelta is being investigated in a pediatric AML indication. This is also a registrational study. Can you just take us through a little bit of the details there, and ultimately, when we might expect to see some data from this indication, whether it could be an accelerated approval pathway?
So we haven't guided on specific timelines for the trial. But as you mentioned, it is a small trial of maybe 18-20 patients. We do believe that this trial may accelerate the time to market for luvelta and increase the readiness for the much bigger opportunity in ovarian cancer. The trial may also. The benefits of doing a trial like this can satisfy some of the regulatory requirements around pediatric studies, both in the U.S. and in EMA, and also come with potentially a priority review voucher, which is worth about $100 million on the street value, and also can potentially benefit or extend our patent extension. So this is an opportunity to do the right thing for patients and us, and at the same time, a unique opportunity to do the right thing for the business as well.
Excellent. You also mentioned non-small cell lung cancer. There's no shortage of indications that luvelta is currently addressing. I believe, and we'll hit the milestones in the end, but there's data expected in the first half of 2025. What is the kind of internal bogey or hurdle that you need to hit to kind of make that go, no-go decision?
Yeah. I'd like to say it was a response rate of 100%, right? But in our early just to take a step back here in terms of the opportunity in our early translational work, we have seen that FR alpha target is expressed anywhere from 30%-60% in the adeno-non-small cell lung cancer space. And our phase II trial is really in a later recurrent setting. But we are still looking for a meaningful signal in addition to safety in patients. And plan to share sort of a handful of patients probably next year and probably more at the end of the year when we have more of a robust end size. And our initial development plans are really to study luvelta as a monotherapy to understand the contribution of it as a single agent.
But then we'll consider other combinations as we think about what we learn and as we think about moving the therapy forward.
So, is there because when I look at the space, right? There's EGFR wild- type. There's EGFR mutant. There's the KRAS. They all seem to have a particular, call it, response rate that they kind of average around. Is that how we should be thinking about luvelta as well in non-small cell lung cancer? Or is it differentiated in some other way?
Yeah. So it's interesting because I think we would look at it similarly in terms of response rates in the second, third-line setting of what was achieved. I think the opportunity, though, the EGFR mutation patients do express FR alpha a bit higher, but they don't do as well. And so we'll see how this all plays out. The beauty of the trial for us is we're taking a much more inclusive approach. And we are looking at it both with the EGFR mutation as well as wild type patients. And it's interesting how the tubulin payloads could potentially, on these ADCs, be more effective in the wild type setting, which is obviously the much larger opportunity.
I'd be remiss if I didn't ask about your thoughts on the potential for combining this with other drugs, and if so, what are the ideal sort of drugs that you think, either from preclinical experience or just as you're thinking about the landscape, what would be the ideal combination drugs to evaluate?
Yeah. In our preclinical work with luvelta, we have seen activity not only as a monotherapy, but also in combination with a PD-L1. And that is a very good thing because we know these anti-PD-L1s are commonly used in lung cancer. And so to be able to combine is also a strategy that we would consider. I realize that there's new treatment options that are now being explored and actually showing benefit, like ivonescimab, which has come out with new data in the front-line setting. And that's really great that the treatment options are further expanding in lung cancer.
As those therapies are sort of showing benefit in an earlier stage front-line setting, the initial approach for luvelta would be looking at the more later stage recurrent settings and then first explore it as a monotherapy and then potentially as a combination, either with an anti-PD-L1 or a bispecific moving forward.
Got it. Maybe in the time we have remaining, a little bit of some of the other areas that you're looking at. You've announced, I think, at the forum that you hope to have three INDs over the next three years. Would love to kind of just get your sense as to how you see these next molecules kind of evolving and how you feel that these novel molecules you had mentioned, I think, a couple of things in your preparatory remarks, those being kind of first-to-market, first-class, first-in-class molecules being developed. So can you talk a little bit about that pipeline aspect?
Sure, sure. We've been working at Sutro on ADCs for the past 20 years. And we're always looking ahead to where the ADC field is going. And we're very excited about our next generation ADCs, which we showcased at the research forum in October. I believe we're at the tip of the iceberg when it comes to the ADC field with only 13 approvals yet for ADCs. These will eventually replace chemotherapy moving forward. And the challenge or unmet need with all of these ADCs currently is really toxicity. And how high can they be dosed enough to achieve that optimal potency and efficacy? And our unique cell-free capabilities allow us to precisely design these ADCs in a way that very few companies can and avoid some of the liabilities that are commonly associated with more of the conventional CHO-based manufacturing processes.
And it allows our Sutro ADCs to achieve greater exposure as well as, and then potentially, greater efficacy tied to that. Our next ADC is the STRO-004 tissue factor DAR8 ADC. We have designed that with improved site-specific linker strategy as well. In preclinical models, we have seen that it demonstrated greater anti-tumor activity as well as lower toxicities, namely less ocular events compared to a benchmark ADC on the market today. That's really important because tissue factor is actually expressed in the eye. It's an on-target sort of toxicity that you want to avoid. We anticipate filing an IND for that next year. In addition, you'll recall that we did an important collaboration with Ipsen on our DAR8 exatecan ROR1 ADC as well, and also understanding the elegance in the design of that DAR8 exatecan ROR1 in their program.
We have also highlighted the opportunity to make these dual payload ADCs. Again, it is really differentiated from conventional ADCs in that you have two cytotoxic payloads in one product, which really can disrupt the conventional sort of single payload ADCs in terms of overcoming resistance. Potentially, as we move these agents earlier into therapy, they can be sort of a combination therapy all-in-one as a new standard of care. I think this is very exciting in terms of the field. It is being able to design in a way that it is designing, if I could say, on steroids for ADCs, where you can not only mix and match payloads, but do it in the right stoichiometry in terms of two to one, two to two, four to two combination strategies that allow you to really sort of maximize the therapeutic window of these medicines.
Jane, what about the immunostimulatory ADCs? I thought that's quite unique. I haven't seen that anywhere else.
Yeah. I mean, there are so many different ways that you can go after the strategy of engaging the immune system. You could do what the bispecifics have done with the VEGF plus the PD-L1, or you can do an ADC with an immunomodulatory agent plus a cytotoxic agent. And so how best do you sort of incorporate the immune system to be able to attack the cancer and incorporate the T cells in a way that allows you to synergize with the cytotoxic payload is something that is really on the forefront of what we're thinking about. It is definitely very innovative and really the future of what ADCs can do. And the important collaboration we have with Astellas will show sort of highlights on what the promise of that can be.
So speaking of what can be shown and in terms of milestones, I know that you've committed to the IND for STRO-004 for next year. We talked about the part two dose. You have $388 million in cash, so a really good cash forward to kind of fund the pipeline. Anything else here that we should be kind of thinking about or any tweaks to this timing that we have that you think would be important for investors to know?
Yeah. I think really it's really about execution. Over the next six to 12 months, we plan to continue to make substantial progress on our registrational study for luvelta in ovarian cancer, lung cancer, pediatric AML, and hope to have these data presentations targeted at and presented at relevant medical meetings that are upcoming. We'll have two additional product candidates in the clinic, ROR1 licensed to Ipsen as well as tissue factor ADC. And we aim to have two other product candidates progressing in preclinical assessment. And we'll be sharing more information about those exciting next generation ADCs as well. So we're doubling down on innovation, and we continue to execute to make progress on the portfolio.
And I know it's very hard to kind of comment on especially the partnered assets, but any sort of sense as to when we might see how Astellas is moving their particular portfolio of products forward or when Ipsen might release some data?
Yeah. I think that's really dependent and driven by our partners. So I can't share a whole lot there. But these are exciting innovation strategies that will really kind of predict sort of what the field may hold in terms of the next generation of innovation to come in ADCs. And I think we're all excited to partner on these fronts.
Not to ask you.
Yeah. I know. I may not have the answer for you.
No, that's OK.
If I do, I may not be able to share.
No, that's OK, but I think it's always important for investors to know that a lot of this pipeline has been funded by non-dilutive capital with a lot of partners coming in and putting their money where their mouth is, which I think is always a great checkmark, right, for the entire platform.
Yeah. It's a great validation of the technology and the validation of the innovation and investment in the innovation and the potential for the cell-free technology. We've actually been able to achieve a 4,000 L scale of supply. And this is the first time cell-free has gotten to that large scale of production, which really is a big milestone for Sutro because I think folks were potentially skeptical of our ability to get to this milestone. So now that we can actually get to a scale, it's all about delivering on sort of the innovation and the discovery of the pipeline and really leaning into the differentiating aspects of the technology. With luvelta, we've shown that we can make a drug. I think the future is all about how do we lean into what this technology can do above and beyond conventional ADCs.
That's really the focus of the next generation ADCs.
Excellent. Well, thank you very much for the time. Really appreciate it.