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

Greetings, and welcome to the Sutro Biopharma webcast. [Operator Instructions] Please note, this conference is being recorded. I will now turn the conference over to our host, Ed Albini, Chief Financial Officer. Thank you. You may begin.

Thank you, operator. Good afternoon, everyone, and thank you for joining us. With me on the call are Bill Newell, Chief Executive Officer; Dr. Stan Frankel, an esteemed member of our Scientific Advisory Board; Dr. Trevor Hallam, President of Research and Chief Scientific Officer; and Jane Chung, Chief Commercial Officer. We also welcome on the line Dr. R. Wendel Naumann of the Levine Cancer Institute at Atrium Health. This afternoon, we issued a news release that you can find on our website at www.sutrobio.com, which includes an update from our Phase I Dose-Expansion study of STRO-002, also known as Luveltamab Tazevibuli or luvelta in ovarian cancer as well as our plans moving forward in respect to a potential registrational study. The agenda for today is as follows: Bill Newell will open up the discussion. Dr. Wendel Naumann will then present the dose expansion data for luvelta. Bill and Dr. Frankel will provide details around our planned Phase II/III study and the registrational path forward. Bill and Jane Chung will give a brief overview of the market opportunity in ovarian cancer. Bill will then provide brief closing remarks. Last, we will open up the Q&A portion of the call, featuring Dr. Naumann, along with the Sutro team here today. Before we start, I would like to remind you that today's call will include forward-looking statements. These forward-looking statements are based on Sutro's expectations and assumptions as of the date of this call. Each of these forward-looking statements involve risks and uncertainties that could cause Sutro's clinical development programs, future results or performance to differ significantly from those expressed or implied by the forward-looking statements. Please refer to Sutro's filings with the SEC, including our 2021 Form 10-K for information concerning factors that could cause Sutro's actual results to differ from those expressed or implied in the forward-looking statements discussed on this call. Except as required by law, Sutro assumes no obligation to update any forward-looking statements discussed on this call to reflect any change in expectations even as new information becomes available. With that, I would now like to turn the call over to Bill Newell for a welcome and introduction.

Thank you, Ed, and thanks, everyone, for joining our call today. While there has been considerable progress in the treatment of many cancers, ovarian cancer remains an outlier. There is a significant need for newer and better therapies for patients with advanced progressive ovarian cancer, including platinum-resistant ovarian cancer. Today, we will be taking you through the most recent findings from our dose-escalation Phase I study of STRO-002 or Luveltamab Tazevibulin, which we've shortened to luvelta, our novel Folate receptor alpha-targeted antibody drug conjugate. We will also discuss interim data from our newest exploratory cohort, which we call Cohort C, that explore the use of prophylactic pegfilgrastim when given in conjunction with the highest dose of luvelta. Based on these results and our conversation with U.S. FDA last year, we continue to believe that luvelta has the potential to become an attractive new treatment option for patients with platinum-resistant ovarian cancer. luvelta was precisely designed to target folate receptor alpha, a molecular target highly expressed in ovarian and endometrial cancer cells. The target is also highly expressed in a rare pediatric acute myeloid leukemia known as the RAM phenotype. In case you missed it at ASH in December, we presented impressive findings from our Compassionate Use Program involving young children with this extremely rare and aggressive form of AML. But for today, the focus is on ovarian cancer. As you may have already read in this afternoon's press release, our latest results strengthened the convictions we expressed when we presented our interim results a year ago. Luvelta has demonstrated clinically meaningful activity in platinum-resistant ovarian cancer patients who are folate receptor alpha selective, meaning their tumor proportion score, or TPS, is greater than 25%. As a reminder, TPS is the percentage of a patient's tumor cell staining positive for the target regardless of the intensity of that staining. Based on the data generated, we have selected tumor proportion score greater than 25% as the most appropriate scoring algorithm for identifying the target patient population for luvelta. Importantly, this folate receptor alpha-selected patient population potentially comprises up to 80% of platinum-resistant ovarian cancer patients. Therefore, luvelta has the potential to benefit the largest share of platinum-resistant ovarian cancer patients compared to other folate receptor alpha targeted therapies. The additional data and follow-up confirm our interim efficacy results. Folate receptor alpha-selected patients who started at the higher dose of 2.5 milligrams per kilogram had an overall response rate, or ORR, of 43.8%. As a reminder, single-agent chemotherapy, which is standard of care for this patient population has an ORR of approximately 10%. This higher starting dose also showed clinically meaningful median duration of response of 5.4 months and a median progression-free survival of 6.6 months. Furthermore, irrespective of starting dose, patients experienced a 37.5% overall response rate, a median duration of response of 5.5 months and median progression-free survival of 6.1 months. The third important confirmation of our results was that the safety profile has remained substantially unchanged from what was reported a year ago. The primary signal from the dose expansion cohort was predominantly asymptomatic transient neutropenia. Importantly, even though we do not treat patients prophylactically with corticoid steroid eye drops, we are not seeing the sort of substantial ocular events that are seen with other folate receptor alpha-targeted therapies or antibody drug conjugates targeting other antigens. We used Cohort C as an exploratory study to better understand how we might maintain patients on the higher 5.2 milligram per kilogram dose and ameliorate the risk of grade 3 or higher neutropenia. 15 patients with advanced ovarian cancer were enrolled. Our initial evaluation of the first 10 patients in this cohort when compared to patients and dose expansion at the higher dose of 5.2 milligrams per kilogram without prophylactic pegfilgrastim showed decreased rates of neutropenia and dose delays. Specifically, the data demonstrated that rates of grade 3 or higher neutropenia in the first cycle were reduced by 85% and dose delays in the second cycle were reduced by 66.7%. Discussions with FDA last year have provided us with important insights into their thinking regarding Project Optimus and their evolving views on accelerated approval. We took their comments to heart and have now settled on a protocol design to support a BLA. In this single study, we maintain our opportunity for accelerated approval on the same time line as we had previously expected and accelerate by approximately 2 years to full approval opportunity. We think this is the most efficient, cost-effective trial design for luvelta that will provide regulatory authorities with a data package to support approval of luvelta. We expect the registration-directed study to be initiated in the second quarter of 2023. Moving on to the next slide. The advanced ovarian cancer needs new and better therapies is undeniable. For patients with advanced disease, treatment options have been very limited until recently. And even the newest treatment option is only available to a minority of patients. As Dr. Naumann will attest, platinum-resistant ovarian cancer still represents a high unmet medical need. We designed luvelta to be a next-generation antibody drug conjugate using our proprietary cell-free protein synthesis technology. Our purpose was to create a therapy that could be more broadly effective than other folate receptor alpha targeting molecules with an improved therapeutic index. Luvelta is the first of the new generation of homogeneous ADCs designed to be more efficient and precise at delivering payload to tumor cells to drive immunogenic cell death. We introduced novel specific positions in the antibody for high fidelity attachment of our proprietary hemiasterlin payload and cleavable linker, choosing the best combination of attachment positions ensures maximum impact with every antibody tumor binding [ affect ]. In this way, efficacy has improved over conventional technologies and apparent even in lower antigen expressing tumors. This efficiency of delivery minimizes the systemic exposure to free payload that we believe also minimizes the risk of serious tolerability issues such as ocular damage and pneumonitis. Once the hemiasterlin payload has been released from its cleavable linker and target antigen expressing tumor cells it will then kill secondary surrounding tumor cells. This is known as a bystander effect regardless of target antigen expression. Subsequently, the payload will wash out into the systemic circulation where it is quickly cleared, reducing risk of collateral damage to healthy tissues. This slide details the enrollment of cohorts in our initial Phase I study for patients with advanced ovarian cancer. As part of our dose escalation, we started to see efficacy of the 2.9 milligram per kilogram dose and noted that the top doses of above 6 milligrams per kilogram were not as well tolerated. We initiated the dose expansion phase with Cohort A in January of 2019. Enrollment was in an unenriched patient population, and we require tissue samples in order to be able to determine an appropriate enrichment strategy. We enrolled 44 patients who were randomized between 2 intermediate doses from the dose escalation cohort, 5.2 milligrams per kilogram and 4.3 milligrams per kilogram. As the following data will illustrate, we've now confirmed that a patient selection strategy using a tumor proportion score cutoff of above 25% is the most appropriate patient population for luvelta. 35 of 44 patients in Cohort A were determined to be in the folate receptor alpha selected group. And of those 35 patients, 32 were RECIST-evaluable. As I previously mentioned, Cohort C enrolled 15 patients and the protocol called for patients dosed at 5 milligrams per kilogram every 3 weeks to be treated with prophylactic pegfilgrastim, which was administered on day 8 after each treatment of luvelta. At the time of our data cutoff of December 8, we had initial data on the first 10 patients. The bottom part of this slide shows the patient demographics for Cohorts A and B. And as you can see, the patients were generally well balanced and patients had similar degrees of prior treatment. Of note, the vast majority of patients have previously received bevacizumab and a PARP inhibitor. I would now like to introduce Dr. Wendel Naumann. He is the co-principal investigator in the luvelta Dose Expansion Study and currently Professor and Director of Gynecologic Oncology Research and Associate Medical Director of Clinical Trials at the Levine Cancer Institute of Atrium Health. He serves as a Board member of the Executive Council of the Society of Gynecologic Oncology and the Chair of the Education Committee and a Co-Director of the SGO Winter Meeting. His clinical experience includes targeted therapies and immunotherapies, and he runs the Phase I trials in Gynecologic Oncology of the Levine Cancer Institute. Dr. Naumann.

Thanks, Bill. I'm really excited about these data with luvelta. This is great. And you emphasized the unmet clinical need. It's very frustrating as a physician to have a patient population where the response rate to conventional chemotherapy is 10% or less, and there are very few options. These patients survive only about 12 months. And so we really definitely need new treatments. And as you mentioned, the expansion cohort of 44 patients, there were 41 of these that were evaluable for response. When broken down by folate receptor alpha expression by IHC, 9 patients had a TPS score of less than or equal to 25%. If these patients are excluded, the overall confirmed response rate regardless of starting dose in the remaining 32 -- 32 patients enriched for folate expression was 37.5%. In the next set of figures, the response rate is broken down by the TPS score. Those patients with a TPS score of 25% or less had a confirmed response rate of 11%. And those patients with a TPS score between 25% and 75%, the confirmed response rate was 33%. And for those patients with a TPS score of greater than 75%, confirmed response rate was 40%. For patients with a TPS of less than 25%, the duration of response was short at 2.9 months compared to 5.6 and 5.5 months for the higher expressing cohorts. The last set of figures shows the response rate by starting dose of luvelta. The 16 patients in the folate receptor-alpha selected population got a 4.3 milligram per kilogram dose and a confirmed response rate of 31% compared to the 16 patients starting in the 5.2 milligram per kilogram dose with a confirmed response rate of 44%. The duration of response data demonstrated clinically meaningful durability regardless of the starting dose and the PFS data show important patient benefit even for those who did not reach partial RECIST response folate receptor alpha-selected population. It is important to note the TPS scoring in this trial represents any amount of folate receptor alpha expression, not just limited to those with 2-plus expression or greater. Next slide, please. This is the waterfall plot for the patients who had TPS score greater than 25%. So this represents the folate receptor alpha-selected patients. 22 of the 32 patients or approximately 69% had some benefit from treatment with respect to tumor shrinkage. As an oncologist and as a patient, this is clinically meaningful, as it means you remain on treatment, even though you may not have met the criteria for RECIST-defined partial response. The unconfirmed response rate was 44%, and the confirmed response rate was 37.5% in the folate-enriched group. It's interesting to note that patients who started the 5.2 milligram per kilogram dose had a response rate of 44% versus 31% for those starting at the 4.3 milligram per kilogram dose. In the chart on the bottom right, you can see that the response rate was higher in the 5.2 milligram dose despite the fact that the 4.3 milligram dose cohort had a somewhat higher rate of TPS greater than 75%, that's 56% versus 69%. Please note the folate alpha expression at the bottom of the waterfall plot. Many of the confirmed responses were in patients with a TPS score of less than 75% as denoted by the yellow boxes. The overall disease control rate was 80% in this FR alpha-selected group regardless of starting dose. Given the lack of other options for these patients, this is very clinically significant. Next slide, please. This is a spider plot color-coded based on the dose cohort. The 5.2 milligram per kilogram cohort is dark blue and the 4.3 milligram per kilogram cohort is light blue. The response rate appeared to be deeper and more rapid in the 5.2 milligram per kilogram dose cohort. Patients who achieved a response often had a durable response and several of these patients remained on treatment greater than 1 year. Next slide, please. This is a swimmer's plot of the folate receptor alpha selected group, broken down by starting dose. Of note, 50% of the responses persisted beyond the 24-week landmark as indicated by the dotted vertical line in both the 5.2 milligram per kilogram dose cohort and the 4.3 milligram per kilogram dose cohort. Dose reductions are noted by the lighter blue and gray bars. In the 5.2 milligram group, dose reductions were common, but the duration of response continued after the dose reduction. Also, many of the patients who are on the study greater than 24 weeks did not have a high folate alpha expression as noted by the light yellow boxes to the left of each lane. This demonstrates clinical benefit in patients who would not be eligible to receive other folate receptor targeted therapy that labeled only for higher levels of folate alpha expression. I would like to point out that there were 6 patients in this trial that stayed on for greater than 24 weeks that either did not meet the definition of partial response or had a partial response that was not confirmed but did have prolonged stable disease in clinical benefit. Dose intensity of the 5.2 milligram per kilogram dose was 20% greater than the 4.3 milligram per kilogram cohort, but likely would have been higher as the dose intensity was reduced due to delays secondary to neutropenia. Next slide, please. To address the issue of neutropenia Cohort C looked at the addition of growth factors to the regimen. Due to the half-life of the drug and the timing of the neutropenia the GCSF was given on day 8. Prophylactic GCSF reduced the incidence of grade 3 or higher neutropenia at cycle 1 from 67% down to 10%, decreased dose delays from 76% to 30%. Next slide, please. Overall, luvelta was well tolerated. The most frequent treatment-emergent adverse events greater than grade 2 in 2 or more patients are shown in this table. Neutropenia is the most common toxicity with grade 3 or greater neutropenia in 65% of patients at 4.3 milligrams per kilogram and 76% of patients in the 5.2 milligram per kilogram dose cohorts. In the majority of patients neutropenia was uncomplicated. Arthralgias were the second most common toxicity, 26% patients had grade 3 in the 4.3 milligram per kilogram cohort and 10% in the 5.2 milligram per kilogram cohort. Of note, all of these patients are pretreated with paclitaxel were likely to have some baseline neuropathy, which would make arthralgias worse. Of significant interest there was rare grade 3 or greater ocular toxicity and no -- greater than grade 3 pneumonitis has been associated with other ADCs. There were several grade 3 events that were felt to be unrelated to study drug, including large and small bowel obstructions due to the progression of metastatic disease. And acute kidney injury that was attributed to other factors, including sepsis and dehydration. There are also 2 pulmonary emboli that were felt to be unrelated to the study drug. Overall, luvelta had an excellent efficacy in patients with platinum-resistant ovarian cancer had a TPS score, folate receptor alpha of greater than 25%. Luvelta was well tolerated and not associated with higher frequencies of clinically relevant toxicities seen in other antibody drug conjugates that have been used to patients with ovarian cancer. I'm going to turn this back over to Bill for an overview of the registration pathway for luvelta. Thanks.

Thank you, Dr. Naumann. Based on these results, we're ready to move into our registrational-enabling study. We believe our target product profile is strong with the potential to treat approximately 80% of platinum-resistant ovarian cancer patients with equal or better efficacy than the recently approved folate receptor alpha targeting therapy and with a more tolerable safety profile, particularly for the higher dose in light of the addition of prophylactic pegfilgrastim. I would now like to ask our SAB member, Dr. Stan Frankel, to go through the integrated Phase II/III study design. Stan?

We are excited to initiate the registration-directed study, REFRaME, women with relapsed/refractory ovarian cancer who would otherwise receive single-agent chemotherapy as current standard of care. We have chosen to proceed with a multipart integrated seamless Phase II/III trial design to generate a robust clinical data set that will allow for the potential for accelerated approval while also providing the basis for consideration of a [ regulatory ] approval. We've had helpful discussions with the FDA on Project Optimus and the evolving FDA positions on accelerated approval that have informed our decision. Patients enrolled will be folate receptor alpha selected, meaning our TPS score will be greater than 25%, and they will be platinum-resistant having received 1 to 3 prior lines of therapy, including bevacizumab. In order to provide additional data on dose optimization, the Phase II portion of the study will begin with a randomized run-in dose confirmation phase where we will evaluate 25 patients treated with luvelta, 5.2 milligrams per kilogram with pegfilgrastim delivered prophylactically at day 8 of cycles 1 and 2 and then a step down to dose luvelta at 4.3 milligrams per kilogram. The second arm will enroll 25 patients treated with luvelta at 4.3 milligrams per kilogram without prophylactic pegfilgrastim. Following this run-in phase additional patients will be randomized between 3 treatment arms. The same 2 luvelta dose regimens evaluated in the Phase II dose optimization on one hand and a third standard of care chemotherapy arm. On agreement with FDA on the optimal level to dose, a nonoptimal dose of luvelta will be dropped and the trial will complete its planned accrual. During the conduct of the randomized Phase III portion of the study, when response data and durability data are available, for approximately 110 patients at the optimal luvelta dose. Sutro will assess the overall response rate of the subgroup to support submission of the BLA for accelerated approval. When accrual of the Phase III portion of the trial is complete, full approval can be sought based on progression-free survival as the primary endpoint. REFRaME is expected to begin in the second quarter of this year. Back to you, Bill.

Thank you, Stan. In parallel with our Phase II/III study, we will continue to invest in luvelta and more broadly, including in endometrial and nongynecologic cancers. As I mentioned briefly before, we recently reported positive data with luvelta in pediatric AML at ASH in December, demonstrating the potential to extend benefit of our novel antibody drug conjugate to other patient populations who have a dearth of treatment options. We plan to meet with FDA soon to discuss the clinical path forward in this rare RAM phenotype pediatric disease patient population. As evidenced by a continuously growing data package, we're encouraged about luvelta's ability to reach a broad array of patients and the commercial opportunity ahead. To that end, I would like to welcome Jane Chung, our Chief Commercial Officer; to provide a brief overview of the market opportunity, primarily in ovarian cancer.

Thanks, Bill. So we shared a lot of data with you today. And for commercial, it's important we have a simple story for luvelta. And to that end, I want to make 3 simple points that will shape luvelta's market potential. First is efficacy. Luvelta's efficacy is driven not by a small group of super high folate receptor alpha expressers, but instead by a much broader patient population that includes folate receptor low, medium and high expressors with TPS greater than 25% and all of whom contribute to 80% of patients benefiting from this drug. Second is safety. With the initial look at Cohort C data, we see that luvelta's safety is well managed with GCSF reducing grade 3 neutropenia down to 10% and we're still not observing any clinically notable ocular and lung toxicity seen with other ADCs. Third, testing. With luvelta, folate receptor alpha testing is simplified with TPS or tumor proportion score [indiscernible] only without the need for intensity staining for PS2+ and PS3+ et cetera. So what is the market potential for luvelta. This favorable product profile we just discussed with you gives luvelta multiple shots on goal to drive significant commercial opportunity in gynecologic cancers and beyond. In ovarian cancer, we just discussed the registrational plan for luvelta that would benefit around 4,000 platinum-resistant with monotherapy. We are also studying luvelta in combination with bevacizumab that would benefit an additional 2,000 to 3,000 patients in an early line maintenance setting. We also have an ongoing endometrial trial evaluating luvelta across folate receptor-alpha expression levels. And further beyond, we have a rather unique and large Compassionate Use Program in a super rare pediatric RAM AML, where we've already treated over 17 patients and have shared positive clinical data at ASH and for which luvelta has received orphan drug designation and a rare pediatric disease designation. Importantly, while this may not be a big commercial opportunity, it may accelerate our time line to market and accelerate our readiness for ovarian cancer. In addition, we have some important translational work to do in lung cancer to define the strategies for folate receptor stratification. All of these opportunities make luvelta a pipeline in a drug, and we are excited about the great potential. Next slide. So where does luvelta fit in the overall treatment paradigm in ovarian cancer. As mentioned already, platinum-resistant ovarian cancer remains a very high unmet need. In the current treatment algorithm, illustrated here, stage III to IV ovarian cancer women received platinum-based chemotherapy, [ double ] chemotherapy plus or minus bevacizumab following surgery. These women unfortunately received lots of chemotherapy. And once they progress on a platinum-based therapy within 3 to 6 months, they become platinum-resistant where treatment options become even more limited. Now bevacizumab and PARP inhibitors are important treatment options as they provide more benefit in an early line and in maintenance and the recent withdrawal of some of the PARP inhibitors from later lines to actually lead fewer options for platinum-resistant disease. Recently, mirvetuximab or ELAHERE received accelerated approval, yet their label restricts their use to 30% to 35% of patients with folate receptor outcome of PS2 positive and 75% or greater positive staining as represented by the dark golden circle on the right. Despite the approval, there's still a high unmet need for the remaining 70% of platinum-resistant patients who are either ineligible or unresponsive to ELAHERE. And that is why we are super excited to see luvelta bring meaningful benefit to a broader group of patients, upwards of 80% of patients who have folate receptor alpha TPS greater than 25% as represented by the much larger yellow circle on the right. And the visual on the right is simply to show that the mirvetuximab eligibility is a smaller subset of the larger luvelta opportunity. Okay. I will turn it back to Bill.

Thanks, Jane. As you've heard today, this is an exciting time for Sutro as we prepare for our first pivotal study in an indication in which we believe we can offer a differentiated approach to treating patients who have exhausted their options. As we set out to do when at the onset of the dose expansion study, we've identified an enriched patient population for treatment with luvelta using a TPS scoring algorithm of greater than 25%, which gives us a potential market opportunity of approximately 80% of platinum-resistant ovarian cancer patients. We've seen strong evidence of efficacy regardless of dose level which is as good or better than recently approved folate receptor alpha targeted therapy, and the higher starting dose looks even more beneficial in terms of response rates and PFS. We successfully piloted a cohort that gives us confidence that we can ameliorate the high rates of neutropenia seen in patients who were dosed at the higher dose level by a short course of pegfilgrastim prophylaxis. No new toxicities have emerged and the safety profile does not show the significant ocular toxicities associated with other folate receptor alpha targeted therapies, even without the use of prophylactic ophthalmic corticosteroid drops. And finally, we have a path forward for accelerated approval that is efficient, is most cost effective and is designed in harmony with our data to maximize our probability of success. Our Phase II/III clinical design was informed by our FDA discussion, the advice of our clinical advisers and regulatory experts and the additional clinical data that we now have in hand. We look forward to providing future updates on our development plans for luvelta and to taking your questions in just a moment. On behalf of the entire Sutro team, I would like to thank all of the women who participated in our ovarian cancer studies as well as their families and the investigators and their teams who have devoted their lives to treating these women. We are so grateful for your help as none of this would have been possible without you. And with that, operator, you may open up the lines for a question-and-answer period.

[Operator Instructions] Our first question comes from Roger Song with Jefferies.

Congrats for the impressive data. A couple of questions from us. The first one -- just help us to interpretate the consistently longer PFS than the DOR. What is the potential driver for the longer PFS than the DOR and how clinically meaningful the data is appreciating this is single-arm clinical trial.

Thanks, Roger. We have a lot of stable disease that we're seeing in patients, and that really is what is driving the higher degree of progression-free survival. And this is -- as we talked about during the slides that were presented, this is something that we think is what we were trying to achieve with this molecule, which is disease control, not only for patients who respond but for women who do not respond, and we're really pleased to see the progression-free survival numbers at this early stage. Of course, we've been piloting the right treatment strategy for these doses. And I think Cohort C gives us confidence to move forward with a dose level that we believe could have even better benefit in terms of duration of response and ultimately, progression-free survival in future studies.

Got it. Yes. That makes sense. And also just a question related to the Cohort C. The safety profile, particularly for the neutropenia is very impressive, kind of very improved. But would you report efficacy data from that cohort, I mean, knowing you will do the run-in phase for the dose confirmation in your pivotal. But what is your kind of strategic assumption for the delta of DOR -- ORR and DOR and the compared to the -- without the GCSF.

So let me just really answer the question in this fashion. We wanted to understand whether prophylactic pegfilgrastim could significantly reduce the amount of grade 3 or grade 4 neutropenia, and this initial look at the data, which is really relatively mature but important suggested that right at the outset, we're able to ameliorate the risk of that and that we're able to actually keep patients on treatment with much fewer dose delays at cycle 2. Now obviously, we have a 15 patient cohort here that is going to be treated and going to hopefully have good duration of response to the extent they respond and good progression-free survival but it is way too early to have any data at that level. As we move forward this year and as we get that data, we'll look to talk about it in the future. But really, the cohort was designed to answer the question about ameliorating high-risk neutropenia.

Got it. Okay. Maybe just last from -- for the pivotal study design, you have the control arm as the standard of care, and we know [ mirvetuximab ] they will have the confirmatory study reading out this year and potentially for the full approval if the [ bevacizumab ] is approved, will that be part of the standard of care in the control arm or your control arm is the -- basically is the chemo?

We're looking at standard of care as being chemotherapy in this patient population. That's certainly been something that's been discussed.

Our next question comes from James Shin with Wells Fargo.

Roger dug into the DOR and PFS question, but could you remind us how much of this Phase I population for 002 is going to be reflective with the Phase II design. And then could you remind us how much of this 002 data had bevacizumab exposure?

Sure. So -- in terms of bevacizumab exposure, it was approximately 70% in the folate receptor alpha selected patient population. And given the sample sizes, we really didn't see any differences between -- that were meaningful between patients who are BEV-naive and BEV treated. With respect to the patient population, we did not use prophylactic pegfilgrastim in this study. So really Cohort C is a bit closer to what we're going to be seeing in 1 arm of the study that we're going to do this II/III study. The 4.3 mg per kg dose is exactly as we've been studying it in this Cohort A patient population. And so that's the closest thing that I can say. The starting doses are really intended to give us additional data to satisfy Project Optimus but we're optimistic that the 5.2 mg per kg dose with pegfilgrastim will prove to be the right dose for this patient population.

Appreciate it. And one more, if I may. Going to the DOR and PFS, could I ask Dr. Naumann or Bill yourself, which is the better metric in this population? It sounds like PFS is and DCR is still valuable in the setting. Is that kind of the way to think about things?

So I'll let Dr. Naumann answer this, and then I'll be happy to provide perhaps a supplemental comment if appropriate.

Yes. Well, so I think the problem comes down to the fact that if you look at how drugs are actually used in clinical practice versus our sort of the way we do research. We don't look at RECIST defined responses and the progression is -- I'm more worried about the patient progressing clinically. And so I think you get a little bit of an artificial setup here, but it's -- it now has to level the playing field. This is how we have to evaluate drugs. And so for me, it's clinically important for patients to have prolonged stability of their disease. So again, that's -- I think, probably the best way I can say it. Bill, I don't know if you have a better...

No, I appreciate Dr. Naumann you're providing the kind of the practical practitioner perspective, I think, obviously, from a regulatory perspective for accelerated approval, we are going to need good response rates with good duration of response. And clearly, for full approval, we're going to need progression-free survival. So in this study, we're going to get both of those answers on our pathway to getting this drug approved.

Our next question comes from Boris Peaker with Cowen.

First, I just wanted to clarify, in the REFRaME study, should the FDA know how far the randomized part of the study needs to be enrolled for you to file on a single-arm part.

Sorry, can you repeat that question, Boris?

Can you comment -- so how many patients do you need to have enrolled in the randomized part of the study in order to be able to file on the single-arm part of the study. Because we've heard comments from the FDA these days that they want the confirmatory studies largely enrolled before filing on a single-arm trial for accelerated approvals.

Boris, I'm going to ask Stan Frankel, to respond. Thanks, Stan.