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

Good morning, and welcome to the Sutro Biopharma conference call to discuss the updated Phase I data for STRO-002 that was released earlier today. Data from an earlier data cutoff date is also being presented at the AACR virtual annual meeting later this morning. [Operator Instructions] Please be advised that the call is being recorded at the company's request. Now at this time, I would like to turn the call over to Ed Albini, Chief Financial Officer at Sutro Biopharma. Sir, please go ahead.

Thank you, operator. Good morning, everyone, and thank you for joining us. With me on the call from Sutro are Bill Newell, Chief Executive Officer; Dr. Arturo Molina, Chief Medical Officer; Dr. Trevor Hallam, Chief Scientific Officer; and Linda Fitzpatrick, Chief People and Communications Officer. Additionally, Dr. Wendel Naumann of the Levine Cancer Institute is also on the call. This morning, we issued a press release and an 8-K that you can find on our website at sutrobio.com, which includes updated results for dose escalation safety and antitumor activity, reflecting patient data as of April 20, 2020, from our ongoing Phase I study of STRO-002 in ovarian and endometrial cancer. Results for safety and antitumor activity, reflecting patient data as of April 1, 2020, will be presented by Dr. Wendel Naumann this morning at 9 a.m. Eastern Time as a virtual poster at the AACR virtual annual meeting. Slide 2. 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 2019 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 some opening remarks, followed by the data presentation by Dr. Arturo Molina and Dr. Wendel Naumann, and then close with a Q&A session.

Good morning, everyone. Today, we are pleased to share our updated safety and antitumor activity data for our ongoing Phase I study of STRO-002, our homogeneous folate receptor alpha antibody drug conjugate. As a reminder, STRO-002 consists of an antibody targeting folate receptor alpha to which Sutro has in an optimized site-specific manner attached to cleavable linker and a novel proprietary hemiasterlin warhead. The drug to antibody ratio of STRO-002 is 4. There continues to be a high unmet need for new therapies to treat ovarian cancer, and we believe folate receptor alpha has been validated as a target, while other targets remain exploratory. It is overexpressed in 80% of ovarian cancer patients, and there is minimal expression in normal tissues. STRO-002 was discovered and developed using our proprietary XpressCF platform and manufacturing of STRO-002 was initiated at our CGMP manufacturing facility in Northern California. We believe that our CGMP manufacturing facility provides a strategic advantage for Sutro as we control a critical aspect of our ADC CMC process. We designed STRO-002 with the goal of widening the therapeutic window with the potential to improve tumor control and to achieve better patient tolerability than other folate receptor alpha targeted therapies. The data we present today clearly suggests that optimally designed ADCs can achieve both of these objectives. As a reminder, in this Phase I study of STRO-002, we are enrolling patients without knowing their levels of folate receptor alpha expression. Importantly, the 30 ovarian cancer patients in this dose expansion, dose escalation phase of our study are very heavily pretreated and had a median of 5 prior lines of therapy. Dr. Molina will break those down, those prior lines of therapy down momentarily. As you will hear, these patients entered our STRO-002 trial with very advanced disease. The prior study suggests that patients who have had 5 prior lines of therapy should not expect much in the way of disease control and are more likely to be susceptible to adverse events because of the toxicities associated with their numerous prior therapies. As you will see in the slides to be presented shortly by Dr. Molina with comments by Dr. Naumann in patients who were dosed at the more therapeutically relevant dose levels of 2.9 milligrams per kilogram level or higher, 62% of evaluable patients, meaning at least one CA-125 measurement after cycle 1, day 1 had reductions in CA-125 levels of 50% or more or normalization of CA-125 levels. 35% of patients, that is 7 patients who are evaluable for disease progression has stayed on study for longer than 24 weeks. Importantly, an additional 11 patients at 5.2 milligrams per kilogram or higher are on study and have not yet reached the 24-week evaluation point. 75% of ovarian cancer patients have initial post baseline scans showing stable disease or partial response. And finally, 100% of patients, that is 12 patients who have had a CA-125 reduction equal to or greater than 50% or normalization and who are evaluable under RECIST criteria also achieved either stable disease, whether confirmed or unconfirmed or a partial response and still remain on study. Dr. Molina will share in more detail that STRO-002 is generally well tolerated. As a reminder, prophylactic treatment with corticosteroid eye drops has not been required to date, even at the higher doses. We report that 89% of adverse events observed are grade 1 or grade 2. Given the number of patients on study so far, the dose levels received and the duration of dosing, we are encouraged by the overall favorable safety profile. And believe that patients and their physicians will value STRO-002's differentiated safety profile and antitumor activity in heavily pretreated ovarian cancer patients in contrast to other available treatments. I will now ask Dr. Arturo Molina, our Chief Medical Officer, to lead us through the data we released this morning.

Next slide, please. Good morning. My name is Arturo Molina, and I'm Chief Medical Officer at Sutro Biopharma. Today, we are joined by Dr. Wendel Naumann from the Levine Cancer Institute in Charlotte, North Carolina. Together, we will be presenting and discussing the interim results of STRO-002-GM1 on behalf of our core investigators. Our initial STRO-002-GM1 presentation at the ERTC NCIA CR triple meeting in Boston on October 29, reported a preliminary analysis of data on 13 patients analyzed up to October 15. Dr. Naumann will be reporting data on 27 patients analyzed up to April 1, 2020, in a video poster presentation at today's ACR Virtual meeting. And today, during this call, we will present an updated, again, interim analysis on 30 patients based on data analyzed up to April 2020. Next slide. This is a Phase I first-in-human study of STRO-002 in patients with advanced platinum resistant or refractory epithelial ovarian cancer. This Sutro sponsored study was initiated in March 2019. It is being conducted at 10 centers throughout the United States. The trial has enrolled 30 patients with recurrent, heavily pretreated platinum resistant or refractory ovarian cancer. It is important to note that patients are being enrolled without regard to folate receptor alpha expression or the number of previous chemotherapy regimens. The primary objective of the Phase I portion is to determine drug safety, the maximum tolerated dose, recommended Phase II dose, PK data and preliminary efficacy. The trial employed an accelerated dose titration design with single patient cohorts for the first 2 dose levels, followed by a standard 3 -- plus 3 design for subsequent dose levels. The trial is still enrolling, and the MTD has not been reached. Can we move to the Slide #5. The patient demographics and characteristics are shown in this slide. The median age of the patients enrolled is 60.5 years, with a median time from diagnosis of 3.9 years. The population enrolled in this trial was heavily pretreated. The median lines of prior therapies is 5, with a range of 2 to 10. 100% of patients have received platinum-based regimens. And of these, 40% of patients have received 3 or more platinum-based regimens. 97% received taxanes, 77% received bevacizumab, 60% received PARP inhibitors and 23% received checkpoint inhibitors. In addition, 37% of patients also received experimental treatments. As a benchmark, this is a more heavily pretreated patient population that has been reported for -- other folate receptor alpha targeting antibody conjugates during dose escalation. Dr. Naumann, or I will turn to Dr. Naumann, what type of responses do you expect to see in a heavily preceded patient population like this? And specifically, in patients who have progressed after 3 lines of platinum-based therapy?

Yes. Yes, this is a very heavily pretreated group with ovarian cancer. And although ovarian cancer responds well to first-line therapy, as you progress in lines of therapy, responses become much less common. Generally, after a third line, we see a 10% to 15% response rate in third line. And in fourth line, we would expect a response rate of less than 5%, and that's without regard to platinum sensitivity. We rarely see any responses after six line therapies. And once patients develop platinum resistance or recur within 6 months of platinum treatment, response rates are less, and they're generally in the 5% range regardless of line of therapy, and they drop if they've had previous treatment. So we don't have any treatment really beyond third line for patients with ovarian cancer in a broad sense. And I want to emphasize in this data set, the percentage of patients with experimental therapies was over 1/3. And it just shows that these patients have very few options left. Most of the patients that I enrolled in this trial would have gone to hospice, had it not been for this trial, and there's a lot of demand for this. And right now, I have a waiting list of over a dozen patients for this trial.

Thank you, Dr. Naumann. We will now move to Slide 6. This slide shows the spider plot of the CA-125 levels of 21 patients on trial treated at dose levels greater than or equal to 2.9 milligrams per kilogram who are evaluable with a post baseline assessment. 62% or 13 of 21 patients had either normalization of the CA-125 level or a greater than or equal to 50% reduction from baseline. Of the 13 patients with a CA-125 reduction, 6 were confirmed as a CA-125 response on a second evaluation 28 days later for GCIG criteria. One patient had sustained normalization of CA-125 from baseline, and 6 ongoing patients had unconfirmed CA-125 reductions greater than 50% from baseline and will be assessed for confirmation at follow up visits. 4 additional patients that are not included in the total of 21 reported in this figure, have not reached the first post cycle 1 day 1 CA-125 assessment. I will now ask Dr. Naumann to comment on the potential clinical significance of these CA-125 responses on normalization. Dr. Naumann?

Thanks. So CA-125 is a very good marker that we use clinically every day in managing patients with ovarian cancer. And although the FDA has really not embraced this as a response marker, it is -- it's important to understand the clinical practice with ovarian cancer is to follow patients with CA-125 level in base CT assessment on the CA-125. Ovarian cancer is exceedingly difficult to measure on CT because of the nature of the cancer. Many of these patients get carcinomatosis, which can't really measure on CT scan. And that's the problem with resist based criteria. We see also, particularly in Phase I trials, patients that have clinical progression that we can't measure on CT scan. I think this is -- it could be problematic except these patients do exceedingly poorly because those patients generally die within 30 days of clinical progression coming off trial. So again, I think the CA-125 is a good piece of evidence about activity of drugs even if we can't measure this by true resist criteria.

Thank you, Dr. Naumann. We will now move to Slide 7. This summer plot of patients treated at dose levels of greater than or equal to 2.9 mg per kg, demonstrates that 68% or 17 out of 25 of patients are still on study treatment. Individual patients are arranged according to dose level, going from the 3 patients on the top at the 2.9 mg per kg and then the patient treated at the highest dose so far, 6.4 mg per kg at the bottom of the graph. At declaring the 6.0 mg per kg dose level in consultation with the safety evaluation team with 7 enrolling additional patients at 5.2, 5.6 and 6.0 mg per kg dose levels to better understand the safety profile and define the recommended Phase II dose. The yellow arrows indicate the patient remains on study treatment, while the Orange hexagons indicate patients that have discontinued study due to disease progression. An important observation depicted in the surmise plot is that 35% or 7 of 20 patients evaluable for progression, have remained on study for greater than 24 weeks, implying a preliminary or potential clinical benefit rate or disease control rate of 35%. 11 patients treated at 5.2 mg per kg and above remain on study and can potentially reach the 24-week time point, which is clinically significant milestone. Of these patients, 6 have not had a second scan assessment and 5 have not yet reached their first scan assessment and are not evaluable. Follow-up is still early. The median number of doses administered to date is 3 with a range of 1 to 5. So I will now turn to Dr. Naumann and ask him to comment on the significance of this initial duration and study assessment and the significance of 16 weeks versus 24 weeks as a milestone. Dr. Naumann?

To put this in perspective, I think it's important to remember that the life expectancy of these patients is generally in the 6 to 12 month range. So if I see good disease control at 6 months, that's really promising and clinically meaningful to these patients. If you look at these data, right now, there are 7 patients who are on study more than 6 months and 7 that progressed within 6 months. So really, half of the patients that we can assess at that time period have either -- have stayed on study. So again, as you pointed out, there were 11 patients who were at the higher dose levels who can't be evaluated yet. So just to put this in perspective, all of the GOG 126 Phase II trials in first-line platinum-resistant ovarian cancer, the 6-month PFS was about 16%. So it's pretty significant from a clinical standpoint.

Thank you, Dr. Naumann. We will now move to Slide 8. Patients were evaluated for response, stable disease or disease progression by CT scans at 6 weeks, [indiscernible] then every 9 weeks. 75% or 15 out of 20 patients treated at dose levels greater than or equal to 2.9 mg per kg, have initial post baseline scans showing stable disease or partial response. Evidence of anti-tumor activity to date includes 1 patient with an ongoing confirmed partial response who remains on study for more than 36 weeks. 5 patients with confirmed stable disease per RECIST criteria, including 3 patients at 18 weeks or beyond and 2 patients at 27 weeks. In addition, 9 patients had unconfirmed stable disease at the first post baseline assessment. Of these 9 patients 2 progressed and 7 are awaiting follow-up stance. Follow-up is still early in 5 out of 30 patients or 20%, are awaiting their first post baseline scan and not yet available for RECIST response. I will now ask Dr. Naumann to give us his view on the data presented on this slide, specifically, that 75% of evaluable patients treated at 2.9 mg per kg higher have no evidence of disease progression by RECIST at the time of their first post baseline scan. Dr. Naumann?

So patients on these types of trials generally do very poorly. And we lose as many as 40% to 60% per assessment cycle. So to see 75% of patients stay on treatment past the first assessment is certainly a good sign. And again, long-term stable disease in these patients is clinically meaningful. So I think that's really -- these patients really have no other treatment options. So I think this is, again, clinically meaningful data.

Thank you. We'll now move to Slide 9. We have evaluated the combined CA-125 and RECIST responses for all patients treated at dose levels greater than or equal to 2.9 mg per kg. All 12 out of 12 evaluable patients are 100%, who achieved either a confirmed or unconfirmed CA-125 reduction or CA-125 normalization remain on study treatment. And all 12 of these patients have also demonstrated tumor control for RECIST. 1 patient with an unconfirmed CA-125 response has not yet received a post baseline scan assessment. 4 ongoing patients have not had their first-line -- post baseline CA-125 assessment. So Dr. Naumann, what is your view on the relationship between CA-125 responses as a potential indicator of achieving disease control? And do you have any other thoughts on the data presented on this slide?

Yes. Well, I think it's no surprise that the CA-125 predicts tumor control. As we know, CA-125 is much more sensitive than CT scans. And certainly for recurrence, will proceed CT evidence of recurrence by as much as 6 months. So it's reasonable to assume that a decrease in CA-125 predicts patients who are either going to have a response or will stay on treatment for a while. And again, while the FDA has not embraced this as a clinical endpoint for trials, I think the decrease in CA-125 is significant. And in clinical practice, we use the CA-125 more often than we use CT scan based responses for treatment decisions. So I think the other point is these data are not yet mature, it looks like the unconfirmed CA-125's response. They predict the patients who will stay on study and eventually have a response, particularly those at higher dose levels.

Thank you, Dr. Naumann. We'll move to Slide 10. The treatment-emergent adverse events without causality attribution are shown in this slide. STRO-002 was generally well tolerated and mostly associated with mild events, and 89% of our treatment-emergent AEs were either grade 1 or 2 events. Ophthalmologic exams are performed at baseline and subsequently at every other cycle. Treatment-related ocular science or symptoms requiring corticosteroid eyedrops have not been observed and prophylactic corticosteroid eyedrops have not been necessary, even at the higher doses. The only great for toxicity noted was neutropenia in 21% of patients. In each of these patients, neutropenia has reversed within a week. 2 DLTs have been reported. Neuropathy at the 6 milligram per kilogram dose level and bone pain at 6.4 mg per kg dose level. MTD has not been reached, and enrollment is ongoing at 5.2 mg per kg and 6 mg per kg to better characterize the safety profile and determine a recommended Phase II dose. So I will turn to Dr. Naumann and ask him to comment on the safety profile reported to date and in the patients he has treated on this study.

Thanks. So my experience has certainly been similar to what was shown on the table with relatively mild symptoms. I think from a clinical standpoint, the patients complain most about fatigue and joint pain and neuropathy, partly because they are heavily pretreated and to have some baseline neuropathy. But I think we're getting better at addressing these in the patients who have had bad joint pain. We've added steroids and reduced the dose, and that seems to control the joint pain better. Again, the preexisting neuropathy is problematic because many of these patients have had at least 1 and generally more than 1 cycle of taxane-based therapy. I have a limited experience with mirvetuximab on clinical trial. The few patients I enrolled did have toxicity, I had patients with ocular toxicity, and I had 1 patient with pretty severe pneumonitis as a result of that drive, neither of which we've seen with STRO-002.

Thank you. We'll move to Slide 11. To conclude, the emerging safety profile, evidence of anti-tumor activity and clinical benefit observed starting at the 2.9 mg per kg dose level is encouraging, particularly in this heavily pretreated patient population that is resistant or refractory to platinum regimens and other therapies that has not been enriched for folate receptor alpha expression. 62% or 13 out of 21 patients treated at 2.9 mg per kg or higher doses with post baseline assessments have had a greater than or equal to 50% reduction in CA-125 levels for normalization or sustained normalization of the CA-125. 75% or 15 of 20 patients treated at 2.9 mg per kg or higher doses, have initial post baseline scans showing stable disease or a PR. 100% of 12 out of 12 evaluable patients treated at dose levels greater than equal to 2.9 mg per kg with CA-125 reductions of greater than or equal to 50%, or CA-125 normalization remain in study treatment and achieved tumor control at the time of first post-baseline scan. We move to the next slide. In summary, STRO-002 was generally well tolerated and mostly associated with mild events. 89% of all AEs reported are grade 1 or 2, prophylactic corticosteroid eyedrops are not required, MTD has not been reached, additional patients are being enrolled at the 5.2 mg per kg and 6 mg per kg range to better characterize the recommended Phase II dose. As mentioned, follow-up is still early, and many patients will have a few assessments of CA-125 and scans in the near future. We are very encouraged with the interim results of this ongoing all comers dose escalation study in women with advanced, very heavily pretreated ovarian cancer. We're getting a strong signal of antitumor activity consisting of CA-125 responses in disease control in patients who have exhausted most treatment options. Even though follow-up is relatively short, we are also starting to see patients who remain on study for more than 24 weeks. Our high priority activities for this year will be to confirm the recommended Phase II dose and to initiate an ovarian cancer dose expansion cohort. Additionally, we are currently conducting a retrospective analysis of folate receptor alpha status using our immunohistochemistry assay and will continue this analysis in patients enrolled in our expansion cohort to better understand the relationship between levels of folate receptor alpha expression and efficacy outcomes. We intend to consider the opportunity for future FDA engagement at a more focused -- within more focused patient population data set. So before I conclude, I would like to ask Dr. Naumann, if he has any additional thoughts on the data we're presenting today.

Yes. Thanks. As I pointed out, I'm pretty excited about these data. I also think that the analysis of the folate receptor is critical based on the mechanism of action of this drug, we wouldn't expect patients who are folic receptor negative to have a significant response. And any medication that I can use and heavily pretreated ovarian cancer patients just welcome because the demand is extremely high for therapies that are effective in this patient population.

Thank you. So we will go to the next slide. We would like to thank the patients and their families and are participating study investigators and staff and coordinators for the contribution to the study. I will now pass it on to Bill Newell, CEO.

Thank you, Dr. Naumann, and Dr. Molina. If we could go to the final slide, please. Thank you both for sharing these encouraging interim Phase I data for STRO-002. In the coming months, additional data will be gathered for those patients on study, particularly at the 5.2 mg per kg dose level and higher, and from any additional patients we may enroll. We look forward to reviewing all of the data later this year as to determining our recommended Phase II dose. Once that is done, we plan to initiate before the end of this year, the dose expansion phase of the STRO-002 clinical study. We also look forward to sharing further data update of more mature data from the dose escalation phase of this study by the end of 2020. I want to conclude our presentation by reminding everyone that we have a strong cash position. As of March 31, 2020, we had $129.6 million in cash, cash equivalents and marketable securities. This gives us the opportunity to continue to move forward with our BCMA antibody drug conjugate, known as CC-99712, which is in Phase I dose escalation study being run by Bristol-Myers Squibb. And our CD-74 targeted antibody drug conjugate, STRO-001, which is in a Phase I dose escalation study with updated data expected by year-end 2020. Also, we are encouraged by the initial data from our recently disclosed immunostimulatory antibody drug conjugate platform, and we look forward to updating more on these efforts as the year progresses. Finally, we anticipate additional progress by EMD Serono as they advance our bispecific ADC towards IND filing; Merck in our 2 program cytokine derivative collaboration and our spin out SutroVax on their 24 valent pneumococcal conjugate vaccine, which is heading towards IND. Thank you, and we will now turn to questions. Operator, please proceed.

[Operator Instructions] And our first question comes from Boris Peaker from Cowen.

Congratulations on making this clinical progress.

Thank you, Boris.

I guess my question, maybe let's start on one question on side effect and maybe one on efficacy. On the side effect profile, there was cases of grade 4 neutropenia, believe single case. Just curious, can you give a little more color on that patient, maybe baseline neutrophil counts, any other medication that they may be on to further drive this side effect?

Arturo, will you answer this question, please?

Yes. So the neutropenias that we have seen have resolved spontaneously within 1 week in every case. Some patients have been dosed at 4 weeks, and G-CSF have been used in other patients. There has been no development of neutropenia with fever for acute infections. And this is one of the events that we will be factoring in our decision regarding the dose level we select, and the dosing schedule of 3 versus every 4 weeks.

Yes my question, sorry, was just to understand if there's a baseline characteristics of that patient to make kind of justified neutropenia? Or it sounds like there is nothing there?

Well, many patients are coming in with evidence of bone marrow -- compromised bone marrow reserves. Many patients have had PARP inhibitors, which, as you know, are associated with substantial hematologic toxicity. We still have too few patients to conduct a multivariate analysis, but it is quite possible and likely that the prior treatments influence the neutropenia that we have seen and the taxane use influences the neuropathy and anticipate that the profile will be different as we advance to expansion cohorts where we anticipate treating less heavily petted patients.

Great. And my last question maybe for Dr. Naumann. For these advanced patients, just curious from your experience, how does CA-125 improvement correlate with long-term clinical outcomes that the FDA would look at, let's say, like something like survival?

I think that's excellent -- yes, I think that's an excellent question. We -- as I say, 125 stay down, we know that these patients are not progressing. If you look at data that goes back a ways, to be honest, stable disease is probably as good as a partial response in terms of prediction of outcome, particularly survival. I think it's -- as I said, it's a little difficult to assess these patients by resist criteria sometimes. And that's why the CA-125 from a clinical standpoint, tends to be used more often. And when we see these type of activity or this type of activity with the drug, we would expect that they likely would have survival benefit, although that can be difficult to prove in a clinical trial.

Our next question comes from Ed Tenthoff from Piper Sandler.

Thanks taking our time to walk us through this data. My question has to do on kind of at a high level. Just remind us what CA -- or I'm sorry, what folate receptor alpha levels are broadly in ovarian cancer? And do we see that -- do we see any commits in that as patients progress? So is folate receptor? Does it know if that increases over time? Or is that not necessarily indicative?

Thanks, Ed. Arturo, will you reply, please?

Yes. Our studies have been conducted, not by us, but by other sponsors where archival tissue is obtained on patients. And then patients are enrolled in a study that requires biopsies at the time of initiating treatment and at the time of disease progression. And so in patients treated with folate receptor alpha targeting agents, there's no evidence of modulation or down-regulation of folate receptor alpha expression as the disease progresses. And when compared to archival tissue, there seems to be a pretty good concordance with archival tissue and tissue obtained at the time of a repeat biopsy. These studies have been conducted in relatively small sample sizes, but they do suggest that folate receptor alpha down-regulation or up-regulation is not very common based on sequential biopsies.

Got you. And is there anything special with respect to the immunohistochemistry test that you've designed? Or what should we be thinking about just in terms of sensitivity?

Well, we continue to collect archival tissue provided to us by our study sites and our procurement rate is in the 50% to 70%. And so we have analyzed the tissue in about 16 of these 30 patients. We are anticipating or hoping to get more archival tissue, and then we can present that at a subsequent meeting. For our expansion cohort, patients who do not have archival tissue will be required to have a repeat biopsy for folate receptor alpha expression determination and measurements. At this point, we do not anticipate enriching for a prespecified level of expression, at least not in the first part of the expansion cohort. But as we get more data to correlate expression levels with antitumor activity, we certainly will be likely to require some prespecified level of folate receptor alpha expression. But as Dr. Naumann mentioned, we are not likely to see antitumor activity in patients who have no expression or very large -- That's the data that we need before we -- with our own assay and our own therapeutic, so that we can go to the FDA and propose an enrichment strategy.

Our next question comes from David Nierengarten from Wedbush.

I just had 2 quick ones. First off, on the safety side, just if you could remind us if neutropenia was an expected side effect from animal models or at animal models? And then secondly, on the disposition of the patients at baseline, on the range of medium time and diagnosis that goes as low as 0.6 years. Is there a significant component of refractory patients on -- as in patients who really didn't respond to platinum or only responded for 1 cycle or 2 cycles before moving on to subsequent treatments?

Arturo?

Yes. So the first question, yes, the preclinical studies with a non-human primate showed that the main liability was dose-dependent neutropenia that was reversible up to fairly high doses, and we saw no ocular toxicity. But the reversibility that we saw in the animal studies is at dose levels that we are now at in the clinic. To answer your second question, some of these patients are very refractory. And I can think of a couple of patients who are truly refractory, meaning that they had not had a lot of prior therapy but had grown or progressed within a month or 2 of completing the initial front line platinum treatment. And those patients, I think, are not expected to do very well. I think we have patients who had multiple lines of platinum therapy who are pretty refractory to everything. Our PR patient had 8 prior treatments, including PARP inhibitor and checkpoint inhibitor. So as we get more patients or get final outcomes on the patients we have on the study, it will be easier for us to try to correlate prior platinum -- lines of prior platinum or chemorefractory as or prior PARP inhibitors to levels of anti-tumor activity. But some patients were very, very refractory.

Our next question comes from Reni Benjamin from JMP Securities.

Congratulations on the data update. Maybe just to start off, have you done any sort of correlation analysis between the -- treated patients -- patients and maybe the checkpoint treated patients to see if -- you saw any activity in those prior treated patients versus others? And I guess where I'm going with this is how you might ultimately be thinking about a combination strategy to move the drug more in the front lines of therapy?

Thanks, Reni. Arturo?

Yes. As I just mentioned, we will -- since many patients are still not fully evaluable for response. We have not been able to correlate the prior therapies. But that -- and the impact on anti-tumor activity, but that is high, high on our to-do list. I mean, we will look at whether patients have had 3 or less power treatments versus 4 or more. Obviously, PARP inhibitor is one that we will look at. And this work is ongoing, and we'll be able to provide an update at our next presentation, which we anticipate to be in the fourth quarter of this year, either at the Triple meeting or ESMO.

Got it. And then just as a follow-up, I think to one of the 2 physicians on the call. I think there was a mention of the GOG trial, and they talked about a 6-month response rate of about 16%. I just wanted to get maybe a little bit of context regarding those studies and maybe a little bit more color as to how that data might compare with the study?

Maybe Dr. Naumann, since I think you mentioned.

Yes. So the GOG 126 series was a series of Phase II trials and evaluation of drugs, first-line platinum resistant. So -- and as I recall, they couldn't have had more than 3 priors, but I don't have the criteria in front of me. But again, and this was not a response rate. This was a progression-free at 6 months of 16%. In other words, patients had not come off trial in 16 months compared to the numbers we see here. And I just -- I put that -- so you had some context as to what has been seen with other trials compared to this drug. So it just goes to show you that platinum-resistant patients are very difficult to treat.

Our next question comes from Konstantinos Aprilakis from Deutsche Bank.

Just have a few quick ones for the teams. Considering the MTD has not yet been reached in the Phase I, could you provide more color on the decision to focus on that 5.2 to 6.0 milligram per kilogram dose level range as you try to finalize the go-forward dose for STRO-002? And then have you made a decision as to which folate receptor alpha express levels you plan to include in the dose expansion phase of the trial? Were you exclusively focus on high expressors or it's for lower levels of expression?

Yes. Arturo, please.

Yes, thank you for that question. So although there were no DLTs in the first 3 patients treated at the 6 mg per kg dose level. The safety evaluation team recommended additional exploration of safety at 6 mg per kg before advancing to a higher dose level. Also, because of preliminary evidence of antitumor activity at of 2.9 and 4.3 mg per kg and the observation of the reversible neutropenia, the safety evaluation team thought it would be prudent to investigate the lower doses at 5.2 and 5.6 mg per kg as these could be potential recommended Phase II doses as well. So after additional safety was established with more patients at 6 mg per kg and at the lower dose levels, the SCT recommended a modest dose escalation to 6.4 mg per kg. In that first patient, we saw a DLT of bone pain, at which time Sutro decided to not pursue 6.4 mg per kg at this time, especially since the patients are very heavily pretreated, and they are coming in with compromised bone marrow reserve and as Dr. Naumann mentioned, almost all the patients who have developed neuropathy had it pre-existing and it worsened on treatment, but they had it. They were already in medications for neuropathy. So right now, we're focusing at 5.2 and 6.0, because the goal is to find a dose that we can give over an extended period of time or over multiple cycles. Now your question about folate receptor alpha expression. In the 16 patients, we have obtained immunohistochemistry on, we are using an H score, which quantitates the frequency and intensity of expression. And with 16 patients were -- it's hard for us to make a correlation with activity, given that some of these patients are pretty early in their treatment. But it started to give us a sense of that patients who don't have folate receptor alpha expression are less likely to benefit. And so stay tuned for a more detailed analysis. I think we need to get more samples. But our assay is up and running. It's been vetted with the FDA and the analytical validation process that we agreed to with the FDA is ongoing, and we will be implementing it in the near future in patients where we will be biopsying them and potentially enriching for a certain prespecified level of expression. But at this point, we have not made any decisions. We need more data.

Our next question comes from Asthika Gu Martin from SunTrust.

Thank you for all the color provided on the call today. It's been really helpful and have Dr. Naumann on as well. So I had a couple of questions, if I mind about just a little bit more about the folate receptor alpha level. I know that was not a requirement for study entry, but I'm wondering, apologies if I missed this. Have you looked at that either by or via own test? What that level is after the patient entered the study and you got samples? And if so, have you presented any -- or do you plan on presenting any of that data and time soon? Sort of related to that, I also want to get your thoughts on whether the pool of patients unlikely that are out there might have been skewed a little bit to the folate receptor alpha low side given the other -- the other programs that are underway by other folate receptor alpha targeting agents that are selecting for higher expression? And then I got a follow-up, please.

Great. Go ahead.

Yes. Well, your first question, I just answered, and that is, we are collecting archival tissue, but we are not requiring it. Fortunately, the sites have been very cooperative, and we have been obtaining samples. We have analyzed it retrospectively in 16 out of the 30 patients, and we are waiting or procuring more samples. But we obviously plan to report on this in the future. We are not prepared to report on it today. And then your question about skewing towards folate receptor alpha lower patients, that's part of the information we intend to get as we analyze more samples. But obviously, we know some of our study sites have competing studies where patients are being enriched, and it's something we will monitor and we will factor in as we make final decisions on site selection for our expansion cohorts. But right now, with the patients -- or with the studies that we have, enrollment has been quite brisk. We've had waiting lists throughout all these months. And as Dr. Naumann mentioned, there's a lot of patients waiting to be treated and study.

Excellent. I appreciate that color. Just then, I'd also like to get your feel on this. For the dose expansion, given this data that you're presenting today and as Dr. Naumann alluded to the significance of the long durability of even the stable disease patients, patients with stable disease. How do you expect the recruitment for the expansion to change? Would you expect to see more patients come on with fewer lines of therapy, perhaps a lesser amount of patients which prior experimental therapies? Just trying to get your thoughts, if you can speculate on that.

Yes. I'll take that question. Absolutely. In our dialogue with the FDA as part of the IND, the door is open for us to treat less heavily pretreated patients during expansion, including platinum-sensitive patients. The protocol as currently written, requires primarily one prior line of platinum treatment. We do understand that there will be a lot of competition for patients who are less heavily pretreated. And we are having internal discussions on what our cutoff on the number of prior treatments will be we also want to better understand the activity in some of the subset of patients, for example, how did the patients who have had prior PARP inhibitors do in our study. Those analyses are being initiated. That's an important question because this could inform different registration-directed strategies. If we see activity in a more advanced patient population. For example, patients who have progressed on BEV and PARP inhibitors, that could be a potential pathway for accelerated registration. So we're keeping options open, but we do have the opportunity to treat the heavily pretreated patients during expansion, and we'll be making some decisions in the very near future.

Excellent. One last one. Can you give us some color on the one set of patients who had prior experimental therapies, anything to note there in terms of what they've had?

We just started looking at that. Some of the experimental treatments like intraperitoneal CAR-T against Merck 1 and then some bispecific therapeutics against ovarian cancer associated antigens. Some patients coming in after multiple prior experimental treatments have not done well. Consistent with earlier comments that once patients start going on experimental treatments and progress on those, they've not only exhausted standard of care treatments, but they've already exhausted some of the investigational treatment. So for us, it will be important to study some patients who are not as heavily pretreated or have not progressed on multiple investigational agents.

Our next question comes from Debjit from H.C.

Congratulations on the data. This is Aaron on for by the way. So given the durability of response and the CA-125 reductions, could you quantify the degree of tumor shrinkage in patients with stable disease? And also, have you switched to screening for FR alpha Tier 2 enrollment like requiring it in the new patients being enrolled? Or are you continuing to enroll all coming?

Your second question, we continue to enroll all comers. One of the reasons is we want to see if -- we don't want to ignore the low expressors of medium expressors just yet. It could -- one approach in the future could be to select for the high expressers based on the H score, the way is doing. But I think we want more data to make a data-driven decision on what the enrichment strategy should be. And we will require a biopsy of archival tissue is not available during expansion. But the analysis, at least, initially for the folate receptor alpha will be rental actively retrospectively, until we get a little bit more data. We'd like to get data in about 40, 50 patients, and we're getting there. We just need a little more follow-up on those patients. And I think -- can you repeat your first question?

Sure. So about the durability of response in CA-125 reduction, like -- can you quantify the degree of tumor shrinkage? Is it like a lot of decrease? Or is it a slight increase or pretty stable

We will report that at a future update because some of these patients are still on treatment, like many of them are still in treatment. So we'll have a better sense at the next update.

We'll take our next question from Jim Bargenel from Wells Fargo.

Thanks for providing all the details. This is a few for me. I know it's hard to make cross trial comparisons. But maybe for Dr. Naumann and the team, how would you compare these results to what you'd expect from mirvetuximab in a similarly advanced patient population?

Dr. Naumann?

Again, I think it's a little -- I know people like to look at cross trial comparisons. I think it's extremely difficult because of the types of patients that you get in Phase I trials. But again, I think, particularly the data on CA-125 and the in a stable disease at 6 months is probably more encouraging than what we saw with mirvetuximab. So -- but with my caveat there.

And then do you guys have a sense for the 20 patients where you've got response data and the 15 of 20 where there's disease control, what's the best response to the immediately preceding therapy was? Were these patients that blew through their prior therapy? Or are these patients that responded pretty well previously and might just be good responders? Just trying to get a sense of contextualizing this data versus prior line therapy.

Yes. Yes. So patients come into the study have progressive disease. Some, like the one I mentioned earlier that just blew through the frontline platinum regimen, we get some of those who had been on treatment of 2 for only a month or 2 and had progressed. And then there have been some who had like one patient who had been on PARP inhibitor for 6 months. Some have been done for less. Some have been on for more. We will be looking at all of that. Some patients who got platinum as a third line did not respond. So they all have progressed. But as you alluded to, some patients had an initial response before progressing, and some did not respond to their previous treatment. We have not done that analysis yet. It's one that we -- it's going to also one that will be a high priority for us. That's a very important one. We just have not had time to do that one.

Yes. And let me add -- I put about 8 patients on this trough. And none of them have -- they've all progressed on their last therapy and have no other therapeutic options left.

Great. Maybe just one final question. Just in terms of an enrichment strategy, just trying to understand how difficult it is to get pretreatment biopsies if a lot of these patients have carcinomatosis. And if you have to rely on archival tissue to assess folate receptor status, how reliable is the archival tissue? I think it relates to an earlier question by Ted, but just how stable is folate receptor expression? And can you rely on archival tissue to guide enrichment strategies?

Yes. So I'll answer the second question, and I'll ask Dr. Naumann to comment on the first. For the reliability of our archival tissue, there is a study by Martin who is now at Upenn, she's an investigator in our study as well. And she looked at specifically that question. Archival tissue was obtained in patients who then went on to have a biopsy before starting treatment with mirvetuximab and then a biopsy at the completion of treatment with mirvetuximab. And my recollection is that the concordance rate of archival tissue with the repeat biopsy tissue was in the 70%, like 7-0 percent range. So not 100, but fairly good. And they also saw stability of the folate receptor alpha express at baseline and at the conclusion of treatment. And then for the biopsy, I will ask Dr. Naumann to comment since he and his colleagues are the ones who actually do the procedure. Dr. Naumann, maybe you can comment on this.

Yes, obtaining tissue is, again, if you can use archival tissue, that's usually not a problem because these patients often have a lot of archival tissue. For the most part, we can get some tissue. A lot of times, they'll have a nodule and the residual momentum or something that we would be able to So it's not impossible. But the problem is that the disease progression is with carcinomatosis. And so they have increasing So when you look at RECIST criteria, the presence or absence in is not -- it's not -- you can't quantify it. So it doesn't count in the resist criteria as these patients get worsening on and that's the problem with measuring RECIST criteria as opposed to -- So biasing is not as much of a problem, but evaluating the degree of carcinomatosis is really the issue.

And that does conclude our question-and-answer session for today's conference. I'd now like to turn the conference back over to Bill Newell, CEO, for closing remarks.

I want to thank everyone for participating in today's conference call to discuss our updated Phase I data for STRO-002. We look forward to future updates on CT-99712, STRO-001, our bispecific antibody drug conjugate with EMD Serono, our Merck collaboration cytokine derivative programs, our and our IADC platform. Thank you again, and have a good day, everyone. Stay safe and healthy.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. You may all disconnect. Everyone, have a wonderful day.