Sutro Biopharma, Inc. (STRO) Earnings Call Transcript & Summary

Yes. That's a good question, and I think it's one that's important for people to understand. With any drug like an antibody drug conjugate, you're going to try and give the maximum dose that you can give for a patient. And so people tend to go up to explore the MTD, maximum tolerated dose. In cancer, that's not very useful if you get to a high dose and then the patient has issues that mean you have to take the patient off therapy. And so there's a great example and a drug that just got approved, another ADC, BLENREP. It's a GSK drug. They had a certain amount of ocular toxicity, and they had to withdraw the patients from therapy. Now the drug was still efficacious enough to get approved, but you really don't want to take patients off therapy. So sometimes when you go to too high a dose, you end up actually having this contrary effect of the patient having to go off therapy for an extended period of time. And you lose that hammering of the tumor that you want the ADC to do. So what we did is we took a look at the patients who are responders. And when -- I'm going to put this slide up here, Jim, because I think it makes the point. We were pushing up to the 6 mg per kg dose. And if you take a look at this slide that we've created, you see that our partial responders, leave the top one at 2.9 mgs per kg, had a complete -- had a confirmed partial response and has been on for over a year at this point. But the next 4 people who were partial responders were at the 6 mg per kg dose level. And what you see is that each one of them has had dose reductions associated with some toxicity that they had at the dose level of 6-point mgs per kg. We were able to dose reduce them to either 5.2 or 4.3 mgs per kg, and they were able to continue on study, on the medication and continue to have a response even at the lower dose ranges. And so as we look to balance that high dose versus longer time on treatment at a dose that is better tolerated, we think, and this slide, I think, is really helpful in understanding, that somewhere between 4.3 and 5.2 mgs per kg, you get a lot of efficacy from our antibody drug conjugate, and you get a lot of tolerability that allows the patient to stay on the drug without drug holidays or without dose reductions to levels that are no longer efficacious. We know because of the first patient here that as long as we get to 2.9 mgs per kg, that's going to be a dose that can result in a response in this heavily pretreated patient population. So anything we get above 2.9, we think, is putting more pressure on the tumor. And when you see all of these dose reductions, you have to conclude that 4.3 or 5.2 is probably the area where you can maintain pressure on the tumor without causing the patient to have to be taken off therapy or reduced to perhaps a subtherapeutic dose. So that's a learning that we've had, and we're going to continue to explore that as we move forward into the dose expansion phase of our study. Stay tuned for that because we'll start dose expansion before the end of this year, and we'll talk about our study design. But it's pretty clear to us that 6-point mgs per kg, you can get the same efficacy at 4.3 or 5.2, and it's much more tolerable for these heavily pretreated patients who, frankly, don't tolerate a lot of extra therapy at this point in time. So we're remarkably pleased with the number of patients we've been able to keep on study for 16, 24 and over a year of time. Those are really unprecedented numbers that haven't been seen in comparable studies in dose escalation in ovarian cancer patients.

So Bill, is there anything that you can say about the design at this point of the dose expansion cohort? And if not, maybe in general terms, the ability to turn that into a registration-enabling study. And maybe even more broadly, what is the regulatory path for STRO-002 here?

Yes. I think that, that's a great question. What we started with is obviously the dose escalation to try and understand the profile of our molecule. I think we're pretty close to doing that at this point in time. We are in the process of getting ready for a discussion with FDA about our dose expansion program. And sometime in the next couple of months, we will announce what the dose expansion protocol looks like and, with the FDA's blessing, why we're moving forward in that fashion. But it's going to be somewhere, we think, in the 4.3 to 5.2 mg per kg range. That study, we think we can enroll rather rapidly. And we plan next year in 2021 to have a discussion with FDA about the combined data sets from the dose escalation and the dose expansion portion of our trial and see whether or not there's an opportunity for us to move forward in a way that other companies who are studying ovarian cancer are trying to treat it seem to have gotten FDA approval for. So we know another company was able to secure approval for a single arm, about 100-patient study alongside a confirmatory study that had an active control that is a much larger study and takes much longer to read out because there is such a high unmet need for these patients. Now that study design is interesting because they don't quite have -- they didn't have nearly the efficacy in the dose escalation phase that we've seen to date. They didn't have the long duration that we've seen to date. Now what they are doing is they're moving into a less heavily pretreated patient population. And so as we move from dose escalation to dose expansion, we're going to look to actually go to earlier patients who aren't -- haven't had 5 lines of therapy and haven't been through experimental therapies. We'll be looking for patients who've had about 3 lines of prior therapy. And we actually think the opportunity for our drug to perform better is substantial. Certainly, we know that this other company saw that experience when they went from heavily pretreated to less heavily pretreated. And assuming that we're going to continue to show really good responses, good stable disease, long time on study, we think there's a real good regulatory conversation to be had with FDA that says, "Look, you've allowed some others to go forward with the single-arm study, with the confirmatory study. Our data looks as good. And in fact, I think it will look better. We should have the same regulatory path for us." So that's the chart -- that's the path that we're charting right now, and we look forward to that dialogue with FDA next year. We're close in terms of having adequate data. We think to justify that. But with the dose expansion data, we expect to really be able to be on firm footing when we have that conversation with FDA.

So Bill, you do have another wholly owned program targeting [ C70 ]. But for balance, I think there's a lot of interest in some of your partner programs as well. So maybe we'll rotate to that first. And in particular, with Celgene, Bristol now, the BCMA-targeted ADC. And you mentioned the GSK BCMA ADC. And maybe for context, you could contrast the molecule you've designed for Celgene, Bristol targeting BCMA and what you see the differences are with the GSK molecule. And any sense you have of time lines from your partner side?

Yes. So we're thrilled to be working with Bristol. Celgene was a great partner. And obviously, Celgene is the undisputed leader in the treatment of multiple myeloma, and now Bristol has succeeded that entire franchise. They know, and I think the industry is generally in accord, that B-cell maturation antigen, or BCMA, is really the next high-profile target for the treatment of multiple myeloma after you work through all of the existing therapies. And there is a lot of industry interest in that target. And there are different modalities. Some people are pursuing CAR-Ts. And in fact, Bristol has more than 1 CAR-T therapy available. Some people are pursuing bispecific antibodies, and in fact, Bristol has one of those. The problem with those 2 therapies, and there are a number of reasons why they're very effective, but there are also some limitations, is that they do cause some severe toxicity, including cytokine release syndrome, which means they need to be managed in a very specialized facility and not every patient can get there. Many multiple myeloma patients, as you know, are treated in community oncology centers, and they're just not equipped to manage a patient through cytokine release syndrome, and it happens frequently enough that you really need to anticipate that it's likely to occur. So if you can find an off-the-shelf molecule, one that has got a good degree of efficacy and a good safety profile, then we know that you're going to be able to actually treat many patients who need that next line of therapy. And so that's why Celgene, now Bristol, was excited about our BCMA ADC because that's the exact profile that we have. Now GSK is a little ahead. And as I said, they've got an approval for a drug called BLENREP. It targets BCMA, and the molecule we made for Celgene and Bristol also targets BCMA. They have a linker and a warhead that is different than the linker and the warhead that we have. We actually competed a lot of different warheads to try and identify the best one for this molecule. And so we're using [indiscernible] warhead. The drug antibody ratio is 4, and that is the same as the drug antibody ratio of BLENREP. The difference -- a couple of differences. One, we know that we have a homogeneous single molecule that's in patients. BLENREP is a heterogeneous mixture where the linker and the warhead is attached at a variety of different locations without precision. Two, we know what the profile of the catabolite is. And the profile of the catabolite, because it's the same catabolite that we use on our STRO-001 molecule that you alluded to, the catabolite is one that we think minimizes bystander effect and should enhance the safety profile of the molecule. Now BLENREP had, in its Phase III study, a real interesting patient response rate in the low 30s. And we think that response rate, which was higher in earlier development, got compromised because patients had to go off study because of ocular toxicity. So in their final Phase III study, they studied 2 doses, 2.5 mgs per kg and 3.5 mgs per kg. And what they decided from a registration standpoint was to move forward with the lower dose because the extra toxicity did not confer sufficient added benefit to the patient community. And so that's the molecule that's on study. Last year, Celgene, and now Bristol, started the Phase I dose escalation study, and they disclosed in April that they are already past the 2.5 mg per kg level in the patient dosing that they've done. They have dose patients at 3 mgs per kg, and the next step-up for them was going to be a 4.5 mgs per kg dose level where they were anticipating 3 to 6 patients at that dose level as they move through the dose escalation paradigm. If we've gotten this molecule right, and we don't see ocular toxicity in terms of DLTs or SAEs and either of our STRO-001 or STRO-002 program, and we're hopeful based on the preclinical work that we did, that won't be seen here as well. If we're right, then we've designed a much better molecule that can be dosed and have -- and maintain patients on a higher dose level without ocular toxicity or other toxicities that compromise the efficacy potential. If that proves out, and we hope Bristol will be talking about that this year and next as the Phase I dose escalation study moves forward, this can be a very exciting drug and something that, as I say, is more amenable to many more multiple myeloma patients than perhaps a bispecific or a CAR-T. And it's possible that it could be used sequentially with one of those other therapies as well. And that's something that we think is exciting. Bristol has certainly articulated the view that the antigen target is not lost as a result of therapy. And so it may be that you could start with an ADC like our BCMA ADC and then follow up with a CAR-T to try and finish off the disease state as best you can. So it's a very exciting program. And we look forward to hearing more from them, as I said, either later this year or next as their study matures.

And Bill, we just have 1 minute remaining. And so maybe just to finish off, you alluded to a bispecific ADC that you have partnered. Could you talk about that molecule quickly and the promise you see there?

As I said, ADCs are pretty difficult to make, and making bispecific molecules are pretty difficult to make. And so what we've done with our partner, EMD Serono, is go after a very important target, EGFR, something that they have a huge franchise around. And they wanted something that was more specific. And so we thought, well, let's design a molecule that has 2 binding sites, a MUC1 binding site, which is also a target of interest, and EGFR. And if you're not binding to both sites, the molecule can't get inside and isn't going to cause damage. But if you are able to bind both sites, you get away from those things that only express EGFR, and that gives you some on-target unwanted toxicity to a much more specific molecule. And so what we've done is we've taken the warhead in our STRO-002 molecule, this hemiasterlin warhead that does cause immunogenic cell death. And in a site-specific manner, we've attached it to this MUC1 EGFR bispecific. Now they're finishing up the late stages of preclinical development, very unusual for a large company to talk about that molecule, but they did so at the second virtual AACR conference. And they are taking that molecule in demand in the first quarter of next year for nonsmall cell lung cancer and esophageal squamous cell carcinoma, 2 other indications that there is high unmet need for. So they are excited about taking that molecule into clinical development. We are excited, and we've already made that molecule. So it's ready for them when the trial can start.

Well, great, Bill. We've run through a lot of time and a lot of ground to cover, and thanks for going through all that. Super exciting with what you're doing there at Sutro, and I appreciate you spending the time with us today, and good luck with all the efforts in the fall.

Thanks, Jim. It's good to see you, and thanks for having us here. I'm happy to be able to tell our story on the Wells platform. Really appreciate it.

All right. Thanks, everyone. Have a good day.