Sutro Biopharma, Inc. H.C. Wainwright 28th Annual Global Investment Conference

Jane? Thank you. Thank you.

I am grateful for the opportunity to be here and share an update on the Sutro story. Again, I am Jane Chung, CEO of Sutro since last March. I will be making forward-looking statements as outlined here. With the major transformation we completed last year as a company, we committed to executing three programs into the clinic in three years. We are now on track to actually deliver three programs into the clinic in two years. We presented some recent data on our tissue factor targeting ADC, STRO-004, which is already in the clinic, and we are highly encouraged by the data that we see already, with early activity, seeing clinical responses in multiple tumors outside of just cervical cancer, and favorable safety, as well as a differentiated PK profile, with the next update being in first half of 2027.

Currently, we are dose optimizing between 4-5 milligrams per kilogram, and I am excited to share more information about this program in a few minutes. The next program is STRO-006, which is our integrin beta 6 targeting ADC. Also, much of the design is similar in that it is a DAR-8 Xd-Tcan with a beta-glucuronidase linker. I am excited to share that we are IND cleared and actually activating sites now to start the trial this month. We are on track to actually get these two programs in less than a year into the clinic, which is amazing execution by the team. Our strategy here is really to validate with the single payload ADCs, the optimized linker payload system. In doing that, we want to also then move quickly into a dual payload ADC, by being able to combine different payloads onto one antibody.

You are only able to do that by having a higher safety ceiling. We are very encouraged by the safety we already see for our tissue factor ADC in STRO-004, which helps us really read through the possibilities and the potential for the pipeline and for our dual payload approach. Dual payload approach is really important for us because as we think about overcoming resistance to any tubulin or Topo-based ADCs currently in development, what is next? It is either going to be a novel payload or it is going to be a dual payload, and we are very excited about the dual payload approach that could potentially overcome resistance to any of those payload ADCs. Again, our 227 is on track for IND submission later this year. Here we are combining two different payloads, eight Xd-Tcans and two MMAEs, making it a DAR-10.

Not only are we combining dual payloads, but we are actually taking the DAR even higher than DAR-8, which is really differentiating for our pipeline as well. A real differentiating piece of this is that we can actually dose as high as 25 milligrams per kilogram in NHPs already. I have said this many times, and we fundamentally believe that Sutro has one of the most powerful ADC technology platform. We can optimize every component of an ADC, including the antibody, which we make in cell-free that avoids Fc gamma-related toxicities, but we also have these non-natural amino acids, which we use as the glue between the antibody and the linker payloads to further stabilize the ADC to contribute less free payload in the circulation, which then leads to a better safety profile.

In addition, we have optimized the linker, and we have a beta-glucuronidase linker that cleaves more in the tumor than outside the tumor and also helps with the delivery of the more active drug into the tumor and prone to less of the safety issues in normal tissue. With our payloads, we have moved to an exatecan payload, which is one of the most potent Topo payloads, and we are actually going to higher DARs with the combination of different payloads as well. As mentioned, STRO-004 is our lead asset in the clinic already. This is an optimized tissue factor targeting DAR-8 exatecan ADC with the beta-glucuronidase linker. In preclinical studies, we have 50 times exposure over that of the approved tissue factor ADC.

We believe that tissue factor is an important target here that is expressed in many different solid tumors, of which there is significant unmet need across large oncology patient populations. Here, it should be noted that the current tissue factor ADC, Tivdak, is only improved in cervical cancer. The whole strategy here is to go dose higher and be able to drive greater drug exposure and get to other tumors like pancreatic, head and neck, CRC, and lung that also express tissue factor as a target. Our trial is named STRIVE, is our phase I trial name, and we are currently enrolled all 8 tumors listed here on the left, lung, colorectal, bladder, endometrial, head and neck, PDAC, pancreatic, cervical, and gastroesophageal, all of which are known to commonly express tissue factor.

The dose escalation has progressed from dose level 1 to now dose level 5, and we are now currently optimizing between 4 and 5 milligrams per kilogram, which is at the higher dosing range for any DAR-8 exatecan ADC. I think worth noting is that Tivdak was not able to dose higher than 2 milligrams every 3 weeks, and even other assets coming out of China is still at the 2 or 2.4 milligrams per kilogram. We are actually dosing double in terms of delivering more active drug to the tumor. At the same time, we are seeing very favorable safety that actually shows that it does not come at a compromise on the safety side of things as well.

We are looking forward to the next update in first half of 2027 with more of an efficacy read. We will look to also initiate our expansion cohorts as well in selected tumors of this cohort of 8 tumor types. We will look to feed that into our registrational development strategy. We recently shared an update on our STRO-004 data. It is highly encouraging given in just 7 months, we were able to enroll 49 patients across all planned doses. So far, to see activity this quickly in multiple tumors with confirmed and unconfirmed ongoing responses in PDAC, head and neck, and lung cancer beyond cervical cancer is exactly aligned to the strategy that we set out to achieve here.

Despite the fact that this is a U.S. only heavily pretreated patient population, many of whom in the PDAC and CRC cohorts have already seen irinotecan or been treated with that multiple times. To get that kind of response in these patients is very encouraging for the program. In addition, the safety and tolerability look very favorable. We see low-grade AEs for both hematologic as well as target liabilities for tissue factor. The discontinuation rates are as low as 6% with no discontinuation due to DLTs. This looks very favorable in terms of the safety as well as highly encouraging for the early clinical responses we are already seeing. If we double-click into the PK, we did commit to showing clinical PK in humans, and it is corresponding to what we see in the preclinical data.

Here you will see that we see a dose response, drug exposure response too on the lines above the red zone here of the ADC drug exposure. With every dose higher, you see higher drug exposure levels. In addition to that, we see on the bottom these curves for the free payload exposure, which is maintained below that red zone line of 10 nanograms per milliliter, which is becoming sort of the industry acknowledgement of you want to keep that free payload concentration exposure low to be able to translate into a better safety program with reduced risk of platform toxicity like neutropenia. This is very strong in terms of a PK profile. We see nearly 7 days of a half-life, and that net 98%, we are preserving 98% of the DAR-8 configuration of the ADC at a very high level.

That is also very encouraging for the program as well. This free payload exposure, which has been minimized, now translates into the AE profile that I am going to share with you right now. You will see the AE table here by dose seen in this phase I trial so far. You will see that the AEs are mostly low-grade AEs with limited on target, limited platform toxicity, discontinuation rates, again due to AEs as low as 6%. Here we are very encouraged by the emerging safety profile for STRO-004. The all grade TRAEs greater than 15%, were limited to nausea, fatigue, and anemia.

To see the platform toxicity as low as 6% for neutropenia and 6% for platelet count decrease is actually very differentiating compared to other ADC made through conventional means, exactly what we were trying to deliver and achieve with our new strategy of design, with our optimized design construct for the ADCs. The target-related toxicity increases as you go higher in the dose, which we expected to see because these targets are expressed in normal tissue. The fact that we are seeing DLTs or dose limiting toxicities mostly around target-related events at the higher doses is to be expected, but still the rates are far lower than what we see with competitor ADC products as well, certainly compared to Tivdak. DLTs they occurred all at the 5 milligram and none of that occurred at the 4 milligrams.