Mersana Therapeutics, Inc. (0M40.F) Earnings Call Transcript & Summary

Good morning, and welcome to the Mersana Therapeutics conference call to review interim XMT-1536 Phase I dose expansion data. [Operator Instructions] I would now like to turn the call over to Sarah Carmody, Executive Director, Investor Relations and Corporate Communications. Please proceed.

Good morning, and welcome to our call. Earlier this morning, we issued a press release providing interim data from the ongoing expansion portion of our Phase I study of XMT-1536. This release as well as the slides we will present today are available on the Investors & Media section of our website at www.mersana.com. A replay of today's call will also be made available. After our prepared remarks, we will open the call for Q&A. Before we begin, I'd like to mention that our call will contain forward-looking statements within the meaning of federal securities laws. These are not statements of historical facts and are based on management's beliefs and assumptions and on the information currently available. They are subject to risks and uncertainties that could cause the actual results and the implementation of the company's plans to vary materially, including the risks that are early encouraging preclinical results for XMT-1536 and XMT-1592, are not necessarily predictive of the results of our ongoing or future discovery programs or clinical studies, as the development and identification of the company's product candidates and new platforms will take longer and/or cost more than planned, and that our clinical trials will not be completed on schedule, if at all. These risks are discussed in the company's SEC filings, including, without limitation, the company's annual report on Form 10-K filed on February 28, 2020, the company's Form 10-Q filed on May 8, 2020, and subsequent filings. In addition, while we expect that the COVID pandemic might adversely affect the company's preclinical and clinical development efforts, business operations and financial results, the extent of the impact on the company's operations and the value end market for the company's common stock will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, physical distancing and business closure requirements in the U.S. and in other countries and the effectiveness of actions taken globally to contain and treat the disease. Except as required by law, the company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future. With that, I'll turn the call over to Anna Protopapas, Mersana's President and Chief Executive Officer.

Thank you, Sarah. Good morning, everyone, and thank you for joining us. We are pleased to be able to share this exciting interim data from the ongoing expansion portion of the Phase I study of XMT-1536, our first-in-class and wholly-owned Dolaflexin ADC targeting NaPi2b. This data will also be presented in a poster session at the upcoming ASCO Virtual Scientific Program, this Friday, May 29, starting at 8:00 a.m. Eastern Time. This disclosure marks yet another important milestone for Mersana as we continue to advance XMT-1536 and established proof-of-concept in ovarian cancer and non-small cell lung adenocarcinoma, 2 patient populations with limited options and poor prognosis after failing standard-of-care treatments. This disclosure also represents the fulfillment of the third of our 3 corporate goals for the first half of 2020: XMT-1536 dose escalation disclosure, initiation of clinical studies for XMT-1592 and XMT-1536 interim expansion study disclosure. We are very pleased to once again be joined by Dr. Debra Richardson, Associate Professor of Gynecological Oncology at the Stephenson Cancer Center at the University of Oklahoma and the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Richardson is a leader in ovarian cancer treatment, an investigator in our ongoing trials and the Chair of the Safety Review Committee. On today's call, Dr. Richardson will walk you through this interim data. And then Dirk Huebner, Mersana's Chief Medical Officer, will provide more context on the current standard-of-care and discuss mix steps for this program. Before I turn the call over to Dr. Richardson, I would like to remind you of the characteristics of XMT-1536 and its target NaPi2b as shown on Slide 4. XMT-1536 targets NaPi2b, a sodium dependent phosphate transporter that is expressed on the surface of cells with broad expression observed in the majority of tumors with epithelial serous ovarian cancer and lung adenocarcinoma. With limited expression in normal tissue, these features make NaPi2b an ideal ADC target. XMT-1536 leverages Mersana's proprietary and highly differentiated Dolaflexin platform. Dolaflexin ADCs are designed to have 2 unique features aimed at improving both efficacy and tolerability: First, this ADC has approximately 10 to 12 payloads per antibody with excellent drug like properties, including a long half-life linear PK and very low free payload in circulation. Secondly, XMT-1536 utilizes our DolaLock payload, a proprietary oral study payload with unique pharmacology that allows for controlled bystander killing. Additionally, the highly potent metabolite of the released payload is not a Pgp substrate, thereby avoiding a major mechanism of resistance in cancer. These features differentiate XMT-1536 from other ADC platforms on both efficacy and tolerability based on the data we will present today. Our preclinical studies of ovarian cancer patient-derived xenograft models treated with XMT-1536, such as the relationship between tumor response and NaPi2b H-score. These data and our clinical experience to date strongly suggests the protection of a patient selection strategy for the future development of XMT-1536. We have developed in an immunohistochemistry assay with a broad dynamic range that allows us to classify patients based on their NaPi2b expression. This robust and reproducible assays currently being deployed to retrospectively evaluate NaPi2b expression in tumor tissues obtained from patients enrolled in our clinical studies. We have transferred this assay to a commercial diagnostic partner and are working closely with them to create a commercially available diagnostic assay for use in the registration-enabling study. We're continuing to see an emerging trend between NaPi2b expression and response in our Phase I study. But as we have always said, the total expansion cohort data will be needed to make definitive decisions on patient selection. Note that these data to be presented today have being bifurcated around the same expression level used in the dose escalation study, for both consistency purposes and because the expression levels are not yet available for all patients. In addition, the proportion of evaluable patients falling into the higher NaPi2b population appears to be higher in this data set than the dose escalation or any of the tissue banks we have evaluated. This could be a result of random chance. We will define the patient selection strategy at the completion of the expansion study based on the total data set. Turning to Slide 5. I'd like to briefly review the results of the dose escalation portion of this study, which we presented in March of this year. This data showed that XMT-1536 is well tolerated without the severe toxicities of other ADCs platforms, such as neutropenia, peripheral neuropathy or ocular toxicity. The most common treatment-related adverse events were Grade 1-2 nausea, fatigue, headache and the most frequent Grade 3 treatment-related AE was transient AST elevation without associated changes in bilirubin or cases of Hy’s law. We now understand this lab value to be related to the inhibition of AST clearance by specialized macrophages and not hepatic injury. The patients in the dose escalation portion of the study had a median of 5 prior lines of therapy, and in most cases, had run out of treatment options. Longitudinal studies have shown that this ovarian cancer patients progress, the potential for a response decreases rapidly with line of therapy, and that the expected response rate is close to 0 for these ovarian cancer patients. The fact that we saw multiple confirmed partial responses and durable stable disease in this patent population is very encouraging. We also saw our first confirmed partial response in a non-small cell lung cancer adenocarcinoma patient. In addition, a favorable biomarker response trend was observed for the subset of evaluable patients treated at 30 milligrams per meter squared and above, we had higher NaPi2b expression, 5 out of 15 or 33% of patients achieved partial responses and 6 out of 15 or 40% of patients achieved stable disease for a disease control rate of 11 out of 15 or 73%. In contrast, there were no responders in the low NaPi2b expression group. This is important because it indicates the potential for a patient selection strategy, which can identify patients most likely to benefit from XMT-1536. Slide 6 outlines the current treatment landscape for ovarian cancer patients. The unmet medical need is significant in ovarian cancer with platinum therapy remaining the backbone of treatment in earlier stages of the disease. Recently, bevacizumab and PARP inhibitors have been introduced and are being increasingly used in earlier lines of therapy. Unfortunately, patients inevitably become resistant to platinum therapy. And having previously received bevacizumab or PARP at that point, their options are limited to single-agent chemotherapy such as pegylated doxorubicin in topotecan. In patients with 1-3 prior regimens these agents have limited efficacy with response rates in the 4% to 12% and progression free survival of 3 to 4 months. This is a population we're evaluating in the expansion study. In terms of lung cancer, we saw promising signs of activity in the dose escalation portion of the study. However, as we have guided our experience in treating lung patients, lags behind our experience in ovarian. Today, we will include the lung patients for the expansion, but this data limited have not yet matured. It is important to point out that there remains a significant unmet medical need in this population as well. Dirk will provide more context on the current standard-of-care in this population. Let me now turn the call over to Dr. Richardson to review interim data from the expansion portion of the study.

Thank you, Anna. Good morning, everyone. I am very pleased to be able to join you today to present the interim dose expansion data from the Phase I study of XMT-1536 in patients with ovarian cancer and non-small cell lung cancer, or NSCLC, adenocarcinoma. Before I begin, I'd like to thank my co-authors and the investigators named on Slide 7 for their work on this exciting program. I'll start on Slide 8. 2 cohorts are being enrolled into this expansion study. Patients with high-grade platinum-resistant serous ovarian cancer with 1-3 prior lines of therapy or, in some cases, 4 prior lines of therapy regardless of platinum status; and patients with lung adenocarcinoma who had received prior treatment with a platinum-based therapy and a checkpoint inhibitor or have exhausted targeted therapy if their tumors harbor oncogenic driver mutations. Doses of 36-milligram per meter squared and 43-milligram per meter squared administered intravenously every 4 weeks are currently being explored in the ongoing expansion study being presented here today. Patients began enrolling at 36-milligram per meter squared in August 2019, and the study was then amended to enroll patients at the 43-milligram per meter squared dose in December 2019. The maximum tolerated dose of 43-milligram per meter squared was determined in the dose escalation portion of the study. New patients are enrolling at 43-milligram per meter squared. Patients were not selected for NaPi2b expression. However, archived tissue and fresh tissue biopsies when feasible were collected for retrospective assessment of NaPi2b expression. Turning to Slide 9, which outlines the patient demographics and disease characteristics as of the data cutoff of May 1, 2020. 34 patients were included in the analysis with a median age of 67 years. The majority were ECOG 1 status, ambulatory, but with physical limitations from their disease. 27 of these patients had ovarian cancer and 7 patients had lung adenocarcinoma. The ovarian cancer population had a median of 3 prior lines of therapy and the lung adenocarcinoma patients had a median of 2 prior lines of therapy. All patients with ovarian cancer had received prior platinum and taxane contained therapies with the majority of patients also receiving prior bevacizumab and/or PARP inhibitor. All patients with lung adenocarcinoma had received prior platinum, pemetrexed and immune checkpoint inhibitor. Slide 10 shows the treatment-related adverse events reported in greater than or equal to 10% of patients. Consistent with previously presented data, XMT-1536 was generally well-tolerated with auto-toxicities observed with other ADC platforms, such as severe neutropenia, peripheral neuropathy or ocular toxicity. The most frequently reported treatment-related AEs included generally Grade 1 and 2 fatigue, nausea, vomiting, pyrexia, decreased appetite and transient AST elevation, which recovers by the next dose. No changes in bilirubin or Hy's law cases have been observed and the transient AST elevations are easily monitorable with standard lab tests, peaking on day 8 and self-resolving by the next dose. Further, no Grade 4 or 5 treatment-related AEs have been reported. Slide 11 shows that 21% of patients experienced a dose delay, reduction and/or discontinuation due to a treatment-related AE. Some of the responders, as I will show you on the next slide, achieved or deepened their response while on a reduced dose of 30-milligram per meter squared, enabling dose reduction while retaining activity is an encouraging sign. A total of 18 SAEs have been reported in 10 patients, 2 were deemed to be treatment related. As in any study at this stage, we have been carefully monitoring these SAEs in the safety review committee, which I Chair. Remember, we have now treated approximately 100 patients between the dose escalation and dose expansion and are very encouraged by the overall safety profile of XMT-1536. Turning now from safety to efficacy data on Slide 12. These interim data suggest XMT-1536 continues to be an active drug in ovarian cancer. As shown here, of the 27 patients with ovarian cancer, 20 were evaluable for resist response with at least 1 scan. In the 20 evaluable patients with platinum-resistant ovarian cancer, we observed 2 complete responses and 5 partial responses, not including 1 unconfirmed partial response for which a confirmatory scan is planned, but not available at the time of data cutoff. One of the partial responses had 100% tumor reduction in the target lesions, but nontarget lesions, which are evaluable, but not measurable, remained. The objective response rate is 35%, and the disease control rate is 80%. Moreover, both patients with confirmed complete responses had prior treatment with bevacizumab and PARP inhibitors. These data are very encouraging, especially because it is uncommon to see complete responses in this platinum-resistant patient population. As I mentioned previously, NaPi2b expression is being evaluated by IHC in the archived and where available in fresh tumor tissue and correlation between biomarker expression and clinical response is being explored as part of a companion diagnostic development. These data have been bifurcated around the same expression level used in the dose escalation study for both consistency purposes and because the expression levels are not yet available for all patients. I should note that 2 of the confirmed partial responses represent patients for which we have not yet determined NaPi2b expression. The one responder classified as lower NaPi2b had an H-score of 90, just below the threshold. We will define the threshold once we have the complete data set. Moving to Slide 13. The waterfall plot shows the changes in tumor dimensions of target lesions for the patients as characterized by NaPi2b expression and those where expression is not yet determined. What is exciting about the emerging profile of XMT-1536 is not only the level of activity, but the depth of responses. As you can see, we have 2 complete responses and a third response classified as a partial response with complete elimination of the target lesions. The majority of the stable disease patients achieved tumor shrinkage. The spider plot on Slide 14 includes the 20 evaluable ovarian cancer patients. Another exciting feature about the emerging profile of XMT-1536 is that responses appear to deepen over time. Shown on this Slide 15 is the swimmers plot for the ovarian cancer patients. These data are not considered to mature as approximately 60% of patients remain on study, with 2 patients who have been on study over 6 months and with 6 of the 7 confirmed responses ongoing. One of the patients whose tumor achieved a complete response is highlighted on Slide 16. This is a 70-year-old woman with platinum-resistant high-grade serous ovarian cancer, and was initially treated with XMT-1536 at 36-milligram per meter squared with dose reduction to 30-milligram per meter squared in Cycle 2. Her CA125 normalized after 1 cycle and a partial response with tumor reduction of 63% was observed at the end of Cycle 2, with further improvement to a complete response 12 weeks later. The patient remains disease-free and on-study for more than 6 months. Now to data from the lung adenocarcinoma patients on Slide 17. Data in patients with lung adenocarcinoma are early, with 7 patients enrolled and dosed with XMT-1536. While it is too early to draw conclusions based on limited data, 2 of these patients had higher NaPi2b expression and achieved stable disease. Turning to Slide 18. In conclusion, XMT-1536 has a favorable safety profile with mostly Grade 1 and 2 treatment-related adverse events. Fatigue, nausea, vomiting, pyrexia, decreased appetite, diarrhea and transient AST elevation were the most frequently reported treatment-related AEs. Importantly, to date, there has been no severe neutropenia, peripheral neuropathy or ocular toxicity. Clinical responses, including 2 complete responses, deep partial responses and prolonged stable disease have been observed in patients with platinum-resistant ovarian cancer with a trend towards higher response rates in patients with ovarian cancer with tumors expressing higher NaPi2b. However, more data are needed before a biomarker cutoff point can be declared to prospectively select patients likely to respond to XMT-1536. Finally, I would like to thank the patients, their families and caregivers taking part in the study, and acknowledge my co-investigators and their research staff listed on Slide 19. XMT-1536 continues to show great promise for my patients, and I look forward to working with the Mersana team to advance this important clinical trial. I will now turn the call over to Dirk.

Thank you, Dr. Richardson. We thank you for joining us today to discuss this exciting data. I'll continue on Slide 20. We've very promising data in hand from both the dose escalation and dose expansion portions of the Phase I study, we are well on our way to establish a proof-of-concept for XMT-1536 in ovarian cancer and NSCLC adenocarcinoma. Moving forward, our objective is to enroll approximately 40 to 45 patients in the ovarian cancer expansion portion of the study over the course of 2020. The ongoing expansion study is designed to generate a robust data set to support a conversation with the FDA to initiate a single-arm registration-enabling study meant to support an accelerated approval path. Slide 21 shows the current standard-of-care in the platinum-resistant ovarian cancer setting with a single-agent chemotherapy and multiple contemporary studies have demonstrated the performance of the standard is a response rate of 4% to 12% and the median PFS of 3 to 4 months. Based on precedent and feedback from our investigators and regulatory experts, we believe we have a fast-to-market path using a single-arm registration study, if we can show a response rate that excludes the historical standard-of-care from the 95% confidence in Taxol that is approximately 25% objective response rate, the threshold we have exceeded in both the dose escalation and the current interim readout of the dose expansion. Turning to Slide 22. In the NSCLC adenocarcinoma expansion cohort, our objective is to enroll 40 to 45 patients. In NSCLC, the standard-of-care following progression on checkpoint inhibitors and platinum-based chemotherapy or failure of targeted therapy for patients with tumors harboring oncogenic driver mutations is docetaxel alone or in combination with targeted therapy. The standard-of-care has an overall response rate of 14% to 23% and a median PFS of 3 to 4 months. Our research efforts have confirmed the broad expression of NaPi2b and lung adenocarcinoma while our early dose escalation clinical experience indicates that XMT-1536 had activity, including 1 confirmed partial response and multiple prolonged stable diseases. We look forward to additional patient experience in the lung adenocarcinoma expansion cohort to better define the potential of XMT-1536 to address this important unmet patient need. We are very encouraged with the profile of XMT-1536 both from a safety and tolerability as well as an activity standpoint. We look forward to continuing to treat these patients with high unmet medical needs and advancing this important program towards the pivotal study. I will now turn the call back to Anna.

Thank you, Dirk. We are very excited with this interim data. This data demonstrates that XMT-1536 has a favorable safety and tolerability profile without the severe neutropenia, neuropathy or ocular toxicity seen with other ADCs. We have seen clear signs of activity with confirmed complete responses and partial responses that deepen over time in a patient population with poor prognosis and very limited options. This is particularly promising given complete responses are relatively rare in platinum-resistant ovarian cancer. We also continue to see an important biomarker response relationship, which we believe could allow for a patient selection strategy in a registration-enabling study. We believe this data support the continued development of XMT-1536 and its potential to provide a meaningful clinical benefit to these patients with very limited options. I would like to thank Dr. Richardson and the other investigators working to advance XMT-1536 as well as the many patients and their families who have participated in the study. Before we take your questions, I'd like to remind you of our anticipated goals and milestones for the remainder of the year, as shown on Slide 23. We have now reached 2 of the 3 important data readout milestones for XMT-1536 this year. Our objective is to be able to provide a more mature look at data in ovarian cancer from the expansion study in the second half of the year. We remain on track to deliver on that goal. As we have said, a recruitment in lung adenocarcinoma lags behind ovarian, but we aim to complete the recruitment of this expansion cohort by the end of the year. For XMT-1592 or Dolasynthen ADC targeting NaPi2b, we recently achieved our goal of initiating patient dosing in the dose escalation portion of the Phase I study, and we'll continue to work to achieve rapid dose escalation throughout the remainder of the year. We're also continue to make great progress in advancing 2 exciting pipeline development candidates. We believe we're on track to disclose our B7-H4 and STING ADC development candidates in the supporting data in the second half of the year. In closing, it has been an immensely productive year so far and we look forward to updating you on our continued progress throughout the year. We will now open the call to questions. In addition to Dr. Richardson, we're also joined by the Mersana Executive Team. Operator?

[Operator Instructions] Our first question comes from Jonathan Chang from SVB Leerink.

Congrats on the data. The first question I made it for Dr. Richardson. Can you help us contextualize the quality of responses observed in the study? How common or not are complete responses in the setting?

Thanks for your question. Actually, I'm very excited by the responses we're seeing in this trial. It's very rare to get a complete response in platinum-resistant ovarian cancer. And to remind you what we showed, 2 out of our 20 evaluable patients had a confirmed complete response. And a third patient actually had a resolution of her target lesions. So -- the other thing I'd like to point out is that the responses seem to deepen over time, which is also very promising.

Got it. Maybe I'll just follow-up on that point. While the data is certainly still evolving, how should we be thinking about durability of responses and clinical benefit? And how should we be thinking about the implementations of some of these responses deepening over time on durability?

So I think both are very important. I think the number one thing is the overall response rate because going for registration, that will be the thing that the FDA really locks into. However, it's also -- we'll look at the totality of the data, and it's very important to look at the durability. I think if we can exceed that median PFS of 3 to 4 months or at least match 4 months, we'll be in very good situation for our patients. So we're going to have to look at everything. So response rate and durability are both going to be very important.

Jonathan, I also -- I think it's important to add that at the current state, about 60% of the patients are still ongoing. So the data needs to mature further for us to get a better understanding.

Understood. And just one final question for me. It looks like activity can be achieved at doses lower than 43 mg per meter squared, the starting dose and the expansion cohort. How should we be thinking about the dosing strategy moving forward in the context of dose reductions in the study and the overall safety profile to date?

So -- that's true. What I would say is that we're seeing a safety profile, that's very similar between the 43-milligram per meter squared and the 36-milligram per meter squared. And thankfully, we're really not seeing severe neutropenia, neuropathy or ocular toxicity. So overall, it appears to be tolerable at the 43-milligram per meter squared dose. But it's also important for clinicians to be able to dose reduce their patients rather than having to discontinue a drug. And so it's promising that there -- it does seem to be an activity profile that is adequate at the 36-milligram per meter squared dose as well. So it gives us options.

If I may add, the 2 complete responses were patients who started at 36, we're down dosed to 30 and still achieved complete responses. So we have here a therapeutic window, which allows physicians and treating physicians to really manage their patients and in an effective manner.

And our next question comes from Boris Peaker with Cowen.

Let me add my congratulations on the excellent data.

Thank you.

Maybe Dr. Richardson, an initial question for you. For that one PR with 100% tumor reduction of target lesion. Can you talk about what happened in the nontarget lesion to prevent the RECIST classification of CR? And can that patient still be classified as CR in the future?

So for RECIST, the target lesions have to resolve for CR, but so do the nontarget lesion. So if the nontarget lesion continues, even if it's say 2 or 3 millimeters, we can't call that a complete response. Certainly, we have seen that our slide we showed show that 70-year-old who did eventually get to a CR. So it's certainly possible that the PR could convert into a CR in the future.

Got you. And maybe a question on the biomarker. So I'm just curious for the NaPi2b biomarker H-score, do you have a sense of how repeatable the assay is when performed by different people in different labs at this point? Just wanted to kind of get an understanding between 90, you mentioned one of the patients 110, how big of a difference is that in practice?

So we are still developing the biomarker assay. So I did have the opportunity to participate in Mersana's Assay Development Advisory Board. And it included some of the key investigators, the GLP lab for the assay as well as the commercial diagnostic partner for the assay. So I don't know that we can answer that question yet because we're still under development. And we need additional data from this expansion to know the proper cutoff, but it's very exciting that it looks like we will be successful in developing a biomarker that will allow us to best predict who will respond to the drug.

Great. And just my last question. In the dose expansion protocol, just curious, is there a limit on the number of treatment cycles that patients could get? Or is this a typical treat until disease progression protocol?

It's treat until disease progression protocol.

And we have a question from Debjit Chattopadhyay with H.C. Wainwright.

Just to start off with Dr. Richardson. Would you know what the platinum-free interval was for these patients, for example, the responders versus nonresponders? And the same thing for the 2 CR patients in terms of whether the platinum-free interval was less than 6 months, greater than 6 months or less than -- or between 1 and 3 months?

So all of these patients are platinum-resistant. So they're all less than 6 months. I don't have the exact numbers. I don't know somebody from Mersana would care to elaborate. I don't know if that data was collected. I will say that as far as for the expansion study, we don't allow patients who have progressed within the first 3 months after platinum.

Appreciate that. And one last question for the company. So given the profile that you're seeing for 1536, what is your hurdle for 1592? Or are you primarily working on 1592 for non-small cell lung? And congrats on the data.

So -- yes. Thanks, Debjit. So I think it's full speed ahead on 1536 in ovarian cancer. We're very excited about the profile. We want to complete the expansion cohort and take what we think will be a very robust data set to the FDA and have a discussion about the registration trial. And as we've said before, I think, based on all our interactions with investigators and regulatory consultants and precedent in this area, we believe there's a path for a single non-registration trial, and we're well in a way towards that goal. We look at 1592 as really an opportunity to have a second shot on goal. In lung, we'll be dose escalating through this year. We'll be recruiting the expansion cohort of 1536 through this year and the data we really guide us as to where we go next in lung cancer. But it's full speed ahead on -- with 1536 in ovarian cancer.

We have a question from Mike Ulz with Baird.

Congratulations on the data as well. I just had a follow-up on the biomarker. And maybe -- I know you're waiting for the full data from the study, but maybe you can just comment on your current thinking related to the cutoff. I know you used 110 for consistency but it looks like maybe you need to go lower at 90, but if you ultimately decide to push that down, can you maybe comment on the patient population? Does that increase in a meaningful way? Or is it not meaningful?

Well, I -- as we've said before, if we end up with a cutoff around what we have -- what we put forward at the dose escalation, we think that, that represents about 2/3 of the population. I think the difference between 110 and 90 is difficult to discern in detail, in terms of any changes to the percent population. But we are talking about the majority of the patients. A substantial portion of the patients being above the cutoff and that's pretty exciting that we have the opportunity here to really benefit patients, the majority of patient platinum-resistant patients because the majority of them will be expressing NaPi2b to be above what we expect approximately to be a threshold.

Got it. And then just -- you had 2 PRs that you hadn't determine NaPi2b status yet. Can you maybe talk about the reason for that? And then your level of confidence in being able to determine that in the future?

So it's really a timing issue, Mike. At the time of cutoff, we had not yet received the tissues for assessment. So we will be getting them. We're pretty confident we will be getting them. And when we have our next data disclosure, we'll be able -- in the second half of the year, we'll be able to have a more complete data set.

Our next question comes from Tom Shrader with BTIG.

This is Kaveri for Tom. Congrats on the progress. I just have a couple. Are you studying changes in Napi2b expression in the patients post-treatment?

So we are not getting biopsies post treatment, but we have tried to accumulate as much data as we can on the expression of NaPi2b. We have fresh and archival tissue for the patients who come onto the expansion cohort. We have found tissue banks that -- where we have access to paired biopsies, that is patients that, this is tissue samples from the primary and then the metastatic tissue for a given patient. And we've also had access to awoke biopsy this is a patient who has consented to being biopsied as soon as they pass away which allows us to get tissue samples from different nations. And overall, we see a fairly good concordance in the expression of NaPi2b.

Got it. And from the dose escalation trial, the patients who were treated at 43 mg per m squared dose. Do you plan to include them in the dose expansion study at some point?

To include them in the dose expansion. What do you mean in any disclosure of data in the dose expansion?

Yes. If you plan to provide any more data from those patients that were treated before the screen.

So at some point, we would like to publish the complete dose escalation dataset that would include any -- live any follow-up to the data we disclosed on March 30. We haven't yet guided on exactly our publication timing and strategy.

[Operator Instructions] Our next question comes from David Nierengarten with Wedbush Securities.

Just a quick two, and not surprisingly, on safety and efficacy. First off, on the safety side, you had a couple clotting related AEs. And I was just curious if there are any plans to screen for patients who might have clotting problems prior to the pivotal study? And then the second on the efficacy, just a quick question on BRCA status. So, of course, more than half our PARP experienced. Were there any differences in the response rates that you could tell between BRCA and other negative patients?

So you recognize that these patients come into the trial with a lot of comorbidities, including coagulopathies. And the safety review committee, which Dr. Richardson Chairs, their role is really to review the data on a regular basis and decide for what is a baseline signal and what is potentially a drug effect. I think the one patient with CVA had some specific comorbidities. And I know Dirk has looked into that in detail, and maybe he can comment on that. But before I pass it on to Dirk, your question about patients, whether any of the patients were BRCA positive, the patients were not. A lot of the patients who responded had either PARP or BEV or both. And we do not seem to see a difference in response based on pretreatment. But Dirk, could you comment on the CVA patient?

Sure. I'm happy to. So yes, it's a patient that was reported with an SAE. It's an NSCLC patient and it had multiple comorbidities. So a patient that has included coagulopathy as well as an open heart, and what we call an open foramen ovale between the two atriums. So the possibilities here that these kind of comorbidities and underlying conditions may have contributed to the effect. And then also to answer your question, whether we plan to exclude these kind of patients with coagulopathy in the future? So we look at every case very carefully and do retrospectively reviews with the Safety Review Committee. So it has not emerged as a significant pattern. And we would not exclude those patients moving forward because this is just the way they come into the study and they have these underlying conditions. And having this kind of events is a kind of a typical event pattern that we see and it happens in oncology studies, not just here but elsewhere as well.

Yes I could -- if I could just add to that real quick about the BRCA question. I don't know that we have the exact numbers figured out right now about how many people have BRCA mutations. What I would say is a lot of these patients who had prior PARP inhibitors weren't necessarily BRCA-mutated patients because PARP inhibitors have been FDA-approved now for some time for platinum-sensitive recurrence for maintenance. So many of these patients have received maintenance PARP in that setting.

And I'm showing no other questions at this time. I'd like to turn it back to Anna Protopapas for any closing remarks.

Thank you again for joining us. We're really excited about the promise of 1536 for patients with platinum-resistant ovarian cancer, and we appreciate your time and continued support.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect. Everyone, have a great day.