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

Good evening, and welcome to Mersana Therapeutics' conference call to review updated XMT-1536 Phase I Dose Escalation Study 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 evening, and welcome to our call. A short while ago, we issued a press release detailing the updated clinical data from our ongoing Phase I dose escalation study of XMT-1536. This release as well as the slides we will present today are available on the Investors and 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 I 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 information currently available. They are subject to risks and uncertainties that could cause the actual results of the implementation of the company's plans to vary materially, including the risks that our early encouraging preclinical and clinical results for XMT-1536 are not necessarily predictive of the results of our ongoing or future discovery programs or clinical studies, that the development and identification of the company's product candidates and new platforms, will take longer and/or cross 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, and subsequent filings. 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. And with that, I'll turn the call over to Anna Protopapas, Mersana's Chief Executive Officer.

Thank you, Sarah, and good evening, everyone. I want to start by acknowledging the unusual situation in which we all find ourselves with COVID-19 and thank all of you for taking the time to participate in this conference call. I would also like to thank the Society of Gynecological Oncology or SGO for their flexibility in allowing us to disseminate this important information to physicians and investors. We are excited to share the positive data from our ongoing Phase I dose escalation study of XMT-1536, our first-in-class and wholly-owned Dolaflexin ADC, targeting NaPi2b and discuss our path forward. With this disclosure, we have achieved the first of the 3 important data milestones we announced earlier this year on XMT-1536 and are one step closer to our goal of establishing proof-of-concept in ovarian cancer and non-small cell lung adenocarcinoma, 2 patient populations with significant unmet medical need. The dose escalation information we will present today includes further follow-up on to the interim dose escalation data we provided at ASCO 2019 as well as data on new patients dosed at 30 milligrams per meter squared, 36 milligrams per meter squared and 43 milligrams per meter squared. Although we're seeing encouraging signs of activity in non-small cell lung cancer adenocarcinoma patients, we will focus our comments today primarily on ovarian cancer. As we have communicated previously, the majority of patients on the dose escalation are ovarian cancer patients, and we're joined on today's call 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, an investigator in our ongoing trial and the Chair of the Safety Review Committee. We're very pleased to have her with us today to provide her expert perspectives and to help answer your questions. Dr. Richardson will walk you through the data that would have been presented at the SGO annual conference; and Dirk Huebner, Mersana's Chief Medical Officer, will provide some context on the data and the next steps for the development of XMT-1536. Before turning the presentation over to Dr. Richardson, I would like to remind you of the treatment landscape in ovarian cancer and the patient groups represented in the dose escalation study as well as the patient groups represented in our ongoing expansion study on Slide 4. The unmet medical need is significant in ovarian cancer with platinum therapy remaining the backbone of treatment in early 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 and topotecan In patients with 1 to 3 prior regimens, these agents have limited efficacy with response rates in the 4% to 12% and PFS of 3 to 4 months. This is the population we are primarily evaluating in the expansion studies. As Dr. Richardson will explain, the patients treated in the dose escalation study, have had even more lines of therapy, a median of 5 prior lines and have become platinum-resistant and already progressed on standard of care chemotherapies as well as in many cases, on experimental therapy. Slide 5 represents a number of longitudinal studies that have shown that as ovarian cancer patients progress, the potential for a response decreases rapidly with lines of therapy, triangulating across sources in the literature shows that the expected response rate is close to 0 for ovarian cancer patients like those enrolled in the dose escalation study with a median of 5 prior lines. In this context, the fact that we're seeing confirmed responses in durable stable disease in very heavily pretreated patients is very encouraging. Turning to Slide 6, I would like to remind you of the unique design characteristics of XMT-1536 and its target NaPi2b. NaPi2b is a sodium-dependent phosphate transporter that is expressed on the surface of cells with broad expression observed in epithelial ovarian cancer and lung adenocarcinoma. It has limited expression in normal tissues. These features make NaPi2b an ideal ADC target. Our preclinical studies of ovarian cancer patient-derived xenograft models treated with the NaPi2b ADC, shown on the right, suggest a relationship between tumor response and NaPi2b H-score. Given this observation and the data Dr. Richardson will present today, we anticipate that the patient selection strategy will be a part of the development of XMT-1536. To this end, we have developed an immunohistochemistry, or IHC assay, with a broad dynamic range for measuring NaPi2b expression, an assay that distinguish between higher and lower expressions. This robust and reproducible assay is currently being deployed to retrospectively evaluate NaPi2b expression in tumor tissue obtained from patients enrolled in our clinical studies. In addition, we have transferred this assay to a commercial diagnostic partner and are working closely with them to create a commercially available diagnostic assay for using a registration-enabling study. We are excited to see an emerging trend between NaPi2b expression and response in this early dose escalation study, which will further inform our patient selection strategy for the registrational study, though we are not yet ready to define the biomarker pattern. Moving to Slide 7. As a reminder, XMT-1536 is the first-in-class Dolaflexin ADC. There are 2 unique features to this antibody drug conjugate. First, this ADC has approximately 10 to 12 payloads per antibody with excellent drug-like properties, including a long half life linear PKs and very low free payload in circulation as we have previously reported at ASCO in 2019. Secondly, XMT-1536 utilizes a DolaLock payload, a proprietary, or a statin payload with unique pharmacology that allows for controlled bystander killing. When the ADC is internalized and the payload is first released, it is capable of antigen-independent bystander killing. This payload is then converted to its metabolite, kill the potent cytotoxic, but locked in the tumor cell, where it can accumulate and cause cell death. Additionally, the metabolized cytotoxic payload is not a PgP substrate, a major mechanism of resistance in cancer. We believe these unique features specifically designed into the molecule allows to develop ADCs without the severe toxicities of neutropenia, neuropathy and ocular toxicity, commonly seen with other ADC platforms. We are excited to share this data that do reinforce the important differentiation of our Dolaflexin ADC platform. Let me now turn the call over to Dr. Richardson to review the updated clinical data.

Thank you, Anna, and good evening, everyone. I am very pleased to be able to join you to present the updated dose escalation data from the Phase I study of XMT-1536 in patients with solid tumors likely to express NaPi2b. Before I begin, I'd like to thank my co-authors and the investigators named on Slide 8 for their work in advancing this important program through the Phase I study. I'll start on Slide 9. Shown here is the schematic of the dose escalation of XMT-1536 in the ongoing Phase I first-in-human study. The study enrolled mostly patients with platinum-resistant ovarian cancer and lung adenocarcinoma, who had disease progression after standard treatments. The study is designed as a modified 3 plus 3 design, which allows additional patients at each level. Every 3 and every 4-week schedules were evaluated before moving forward with the every 4-week regimen only. Patients were not selected for NaPi2b expression. However, archived tissue was required for retrospective assessment of NaPi2b expression. As a reminder, the data being presented today is an update to interim data presented at ASCO 2019 and includes additional patients at the 30, 36 and 43-milligram per meter square cohorts. The 52-milligram per meter square dose cohort is currently under evaluation and not included in today's presentation. Slide 10 outlines the patient demographics and disease characteristics as of the data cutoff. As you can see, this was an older population with a median age of 65 years. Both populations were also heavily pretreated, comprised primarily of ovarian cancer with a median of 5 prior lines of therapies and non-small cell lung adenocarcinoma with a median of 4 prior lines of therapies. The majority of patients with ovarian cancer had received prior bevacizumab or PARP inhibitors. All of the lung adenocarcinoma patients had received platinum-based therapies, pemetrexed and immune checkpoint inhibitors. Additionally, many of these patients had progressed on other investigational regimens before receiving single-agent XMT-1536 in the study. Slide 11 shows the treatment-related adverse events reported in greater than or equal to 10% of patients. XMT-1536 was generally well tolerated with a favorable safety profile. There has been no severe neutropenia, peripheral neuropathy or ocular toxicity. There are no grade 4 or 5 treatment-related adverse events. The most common treatment-related adverse events were grade 1 and 2, nausea, fatigue, headache and transient AST elevation. Grade 3 AST elevations have been observed in some patients, but they are transient in nature and recover by the next dose. However, no changes in bilirubin or high phos cases have been observed. And the AST elevations are easily monitorable with standard lab tests. Importantly, the safety profile at the 43-milligram per meter square dose is consistent with that previously reported at lower doses. As shown on Slide 12, XMT-1536 was generally well tolerated at doses up to 43 -- milligram per meter squared and no DLT was reported at the 43-milligram per meter squared dose level. Turning now from safety to efficacy data on Slide 13. Preliminary efficacy data suggest XMT-1536 is an active drug in ovarian and lung adenocarcinoma, the 2 tumor types that are being evaluated in the expansion cohort. As shown here, from the 39 evaluable ovarian and non-small cell lung adenocarcinoma patients in escalation at 20 to 43-milligram per meter square dose levels, higher response rate is observed with higher dose level. This analysis is limited by the number of patients enrolled at each dose level. NaPi2b expression is being evaluated by IHC in the archived tumor tissue and correlation between biomarker expression and clinical response is being explored as part of a companion diagnostic development. On Slide 14, while more data are required to define the biomarker cutoff, we can begin to empirically bifurcate the data at the lowest H-score at which we have observed a response. As shown here, if we divide the dose cohorts into higher NaPi2b, lower NaPi2b and those with indeterminate NaPi2b expression, tumors with higher NaPi2b expression, especially at the higher dose levels, have demonstrated a 33% partial response rate and 73% disease control rate. Whereas, on Slide 15, we can see that no responses have been observed in tumors with lower NaPi2b expression. And on Slide 16, we have observed one response in patients with indeterminate NaPi2b expression. Again, the indeterminate expression is generally due to hypocellular archived samples, not an issue with the assay itself. Moving to Slide 17. These waterfall plots show the changes in tumor dimensions of target lesions for the patients with higher NaPi2b, lower NaPi2b and indeterminate expression. As you can see, at higher dose levels and higher NaPi2b expression, we observed deep responses and stable disease with homer volume decrease. Shown on this Slide 18 are the swimmers plots for the ovarian and lung cohort at doses of 20-milligram per meter squared and above. A meaningful duration of therapy in a population with a median of 5 prior lines of therapy is 2 assessment cycles or 16 weeks. This is a measurement sometimes referred to as the clinical benefit rate at 16 weeks, or CBR16. Approximately 40% of patients with higher NaPi2b expressing tumors remained on study for more than 16 weeks, including 1 patient who remained on study for over 17 months, compared to only 15% of patients with lower NaPi2b expressing tumors. Lastly, slides 19 and 20 show examples of ovarian and lung patient with partial responses who were treated with the 43-milligram per meter squared dose of XMT-1536. First, on Slide 19, is a 43-year old woman with ovarian cancer, who had 9 prior lines of therapy, including prior bevacizumab and PARP inhibitor with an H-score of 110. This is the patient who used to bifurcate the response data by NaPi2b expression. Her CA-125 was elevated over 5,400 prior to coming on XMT-1536, dropped more than 50% after 1 cycle; and after 3 cycles, her CA-125 was 427, with a significant reduction in tumor volume as shown on the CT images. This response was first observed at end of cycle 2 and confirmed at end of cycle 3, and the patient remains on study to date. And Slide 20 shows a response in an 80-year-old patient with lung cancer who had received 4 prior lines of therapy, including an immune checkpoint inhibitor. Again, response was first detected at end of cycle 2 and confirmed at cycle 3. Turning to Slide 21. In conclusion, XMT-1536 has a favorable safety profile with mostly grade 1 and 2 treatment-related adverse events. Nausea, fatigue, transient AST elevations, headache and vomiting were the most frequently reported treatment-related adverse events. Importantly, to date, there has been no severe neutropenia, peripheral neuropathy or ocular toxicity. Evaluation of the 52-milligram per meter squared dose escalation cohort remains ongoing. But based on the data we have to date, it is unlikely that we will proceed further. The first patient experienced fatigue leading to dose reduction in cycle 2. The second patient experienced platelet decreases, which will likely lead to dose reduction. A dose reduction constitutes a DLT. As such, 43-milligram per meter squared will be determined to be the maximum tolerated dose of XMT-1536, and this dose escalation study is closed to further enrollment. 43-milligram per meter squared remains the expansion study dose. Clinical responses and prolonged stable diseases have been observed in heavily pretreated patients with platinum-resistant ovarian cancer and lung adenocarcinoma with higher response rate at doses at and above 30-milligram per meter squared and in those patients with tumors expressing higher NaPi2b. To date, no responses have been observed in patients with lower NaPi2b expressing tumors. However, more data are needed before a biomarker cutoff point can be declared, which can be used to prospectively select patients likely to respond to XMT-1536. As a reminder, based on the ovarian cancer literature, a 5 prior line patient population would be expected to have a response rate near 0%. Finally, the expansion is ongoing at 36- and 43-milligram per meter squared in ovarian and lung adenocarcinoma and is still heavily pretreated in platinum resistant, but more homogenous population, with 1 to 4 prior lines of therapy in ovarian cancer or non-small cell lung adenocarcinoma, failing chemotherapy, PD-1 and for tumors harboring an oncogenic driver mutation failure of targeted therapy. Before I turn the call over to Dirk, I would like to acknowledge and thank the patients, their families and caregivers without whom this study would not have been possible. I'd also like to acknowledge my co-investigators and their research staff. I am very encouraged by the potential of this agent and look forward to working with Mersana to further advance the study of XMT-1536 and having more promising options for my patients who have progressed on the current standard of care.

Thank you, Dr. Richardson. We appreciate your time today. I'd like to spend a few minutes to outline the ongoing trials with XMT-1536. I'll start on Slide 23. The data that Dr. Richardson presented is represented on the left-hand side of this chart and includes a typical Phase I late-line of therapy dose escalation patient population. These are very heavily pretreated ovarian cancer patients with a median of 5 prior lines of therapy. Just as a note, some of these patients had up to 10 prior lines of therapy. These are patients who have progressed on platinum, taxanes, bevacizumab, PARP inhibitors and often other investigational therapies. There is no standard of care for these patients. Multiple published studies demonstrate the drastic decline in response rate with increasing line of therapies. By the third or fourth line of therapy, the response rate approaches 0. This is why we and our investigators are very encouraged by the activity seen in this patient population. The fact that we have seen confirmed responses and durable stable disease in this patient population provides a strong foundation for us to continue to establish proof-of-concept with the expansion portion of this Phase I study. Turning to Slide 24 and the expansion portion of the study. We are enrolling platinum-resistant ovarian cancer patients, who have had up to 3 prior lines of therapy or 4 prior therapies regardless of platinum status. Although the patients in the expansion cohorts are still late therapy line, they are much more homogeneous population than those in the dose escalation study. In ovarian cancer, the standard of care in this setting, a single-agent chemotherapy and multiple contemporary studies have demonstrated the performance of the standard is a response rate of 4% to 12% and a median PFS of 3 to 4 months. After speaking with our investigators, regulatory experts and reviewing precedent, we believe that we have a fast-to-market test using a single-arm registration study if we can show a response rate that excludes the historical standard of care from the 95% confidence interval. Our objective is to enroll approximately 40 to 45 patients in the ovarian cancer cohort over the course of 2020 to establish a proof-of-concept in this patient population. In particular, we expect to be able to determine a NaPi2b expression cutoff in the population where we seek to run a pivotal study. This 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. We are very pleased with the recruitment of patients in the expansion portion to date and believe we will have a substantial amount of patient data to provide a meaningful interim readout in the second quarter of 2020. On Slide 25, as you have seen from the data, XMT-1536 is showing activity in heavily pretreated NSCLC adenocarcinoma patients. Our objective is to enroll 40 to 45 patients in this NSCLC adenocarcinoma expansion cohort. 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 agents. This standard of care has an overall response rate of 14% to 23% and the median PFS of 3 to 4 months. There are fewer precedents for a fast-to-market path in NSCLC, but we continue to evaluate options. The correlation of NaPi2b expression in eGFR and KRAS mutations as we reported at the triple meeting in 2019 raises intriguing possibilities for further patient selection in these high unmet medical need populations. The collection of both archival and fresh tissue in the expansion phase will allow us to better define the patient selection strategy overall. As Dr. Richardson noted, we are very encouraged by the safety and tolerability profile we have observed today as well as the clinical activity we have seen in both the ovarian cancer and NSCLC adenocarcinoma patient cohorts. We are extremely pleased with the progress we are making toward reaching our milestones and the potential for XMT-1536 to deliver a meaningful clinical benefit to these cancer patients. I will now turn the call back to Anna for closing remarks.

Thank you, Dirk. With this data, we have demonstrated that XMT-1536 is a first-in-class ADC, has a favorable safety and tolerability profile without the severe neutropenia, neuropathy or ocular toxicity seen with other ADCs. We have demonstrated confirmed responses in durable stable disease in heavily pretreated patients who have exhausted all other options. In addition, a patient selection strategy is emerging. The expansion cohorts are underway with the objective of achieving proof-of-concept this year and pursuing a faster market registration opportunity in platinum-resistant ovarian cancer. The current COVID-19 situation and its impact on patients and their access to promising experimental medicines like XMT-1536 is something that is on all our minds. We continue to work with our investigators and sites to ensure we are doing all we can to maintain enrollment momentum and continue to benefit the patients on treatment in our study. Even if we see a slowdown in enrollment as the country and the world work to get the pandemic under control, we still expect to have sufficient patient experience from the ongoing expansion study to reconfirm our prior guidance and report interim data in the second quarter of 2020. We will continue to evaluate our options in terms of the venue to disclose this data and issue a press release outlining our plans when appropriate. Finally, I would like to thank our investigators, including Dr. Richardson, who are working to advance XMT-1536 and extend our gratitude to the many patients who participated in the study, along with their families and their caregivers. We look forward to continuing this work and further evaluating the potential of XMT-1536 to provide improved patient outcomes in these important areas of high unmet medical need. We will now open the call for questions. In addition to Dr. Richardson, we are also joined by the Mersana executive team who are also available to take questions.

[Operator Instructions] And our first question is from Jonathan Chang with SVB Leerink.

Congrats on the update. First question, given the biomarker data available and the update here, can you talk about how you're thinking about a potential biomarker cutoff for future development? And also, what percent of the ovarian and lung cancer populations are represented by an H-score of greater than 110?

Yes. Thank you, Jonathan. We are encouraged with the data we've seen and the bifurcation of the data to high and low H-score. However, we think this is a very important decision for the future development of XMT-1536. So we would like some additional data to confirm that before we make a definitive decision on the cutoff. As for the percentage, I believe based on the data we have not only from the clinical -- the patient experience we have, but also work we have done preclinically with tissue banks and patient-derived xenograft models, we believe that the cutoff as we currently see would represent approximately 60% of patients.

Got it. And can you talk about the impact of COVID-19 on clinical development? What are you seeing, and what could that mean for the additional updates you've guided to this year?

Well, as we all know, this is a difficult situation and a lot of the hospitals are under a lot of pressure. We do find ourselves to be in the best possible situation for -- in the context of a very difficult situation because at the time they started, we already had about 20 sites up and running. The investigators in many of these sites have experienced with the drug. They understand the potential benefit for their patients, and we have seen continued enrollment on the trial. Is it at the same rate? Well, it's probably slower and we'll see how the next few weeks go. But we are continuing to enroll in the trial. We have made protocol amendments that allow for remote monitoring and remote testing. So we can -- patients who are benefiting are continuing to benefit. That being said, as we said on the call that even if we -- recruitment slowed down completely or to a significant amount, we do have a meaningful number of patients on trial and we would be able to make a Q2 disclosure as we had committed at the beginning of the year.

Got it. Just one last question for Dr. Richardson. Can you talk about what kind of durability of response do you think is meaningful in this late-line ovarian cancer patient population?

Thanks for your question. I'll remind you, in the dose escalation study, we enrolled patients that had a median of 5 prior lines. Based on previously published data, these patients would have -- be expected to have a response rate of basically 0%. So the fact that we're seeing any responses and also stable disease for prolonged periods is actually quite promising.

Our next question is from Debjit Chattopadhyay with H.C. Wainwright.

Maybe a couple of questions for Dr. Richardson first. Doctor, did you have experience with the Roche program or any of the other folate receptor alpha ADCs? And how would you rate your experience with XMT-1536? And the one case of Grade 3 congestive cardiac failure, how would you consider management of those patients? Or was there something unique about that one patient?

Thanks for your question. I did not participate in Roche's. I assume you're referring to their LIFA ADC trial. I do -- I am familiar with it, and it did show us that it was a proof-of-concept that NaPi2b could be targeted as an ADC. They definitely had some different side effects than we've seen. They've had neuropathy and neutropenia, which were dose limiting, and we have not had those issues with the Mersana XMT-1536 drug. I would also point out that the LIFA study was in earlier less pretreated -- less heavily pretreated patients than ours. I do have experience with the folate drug. So I have studied mirvetuximab. I think they're different drugs. They have different side effect profiles. Mirvetuximab, I have to be careful about what I say what's publicly available, but the ocular toxicity is published and the neuropathy. There's no reason to think that there's overlap between NaPi2b and the folate receptor. So hopefully, both of those will be good options for patients in the future. And then you asked about the congestive heart failure patient. I'm going to defer that answer to Dirk.

Maybe Dirk can take it since it was not a patient of Dr. Richardson's.

Yes, thank you. I'm happy to take that question. So yes, we had a patient who developed congestive heart failure, grade 3. It was a patient on the 20-milligram per square meter dose cohort in the past. We disclosed that patient already at ASCO last year. So there's a couple of things to say with respect to this patient and particularly important is the history of that patient. So the patient had a breast cancer in the history and radiotherapy and a couple of other chemotherapy regimens. So we assume that this potentially has increased the risk of this particular patient to develop such an event. I can tell you from further experience now with this -- within the study, even at higher doses, I mean, up to 43-milligram per square meter, we haven't seen another case like this, and we monitor this very carefully. So it appears to be very well tolerated. And this so far appears to be a very single case without any further cases of such quality.

Great. Thanks for the clarification. So just wanted to clarify a couple of other points. You had 22 patients in the 30 mg per meter square to 40 mg per meter square and 7 in the 43. Do you have a breakdown of how many of these are ovarian versus non-small cell?

Debjit, why don't we follow up with that, so that we're sure we're giving you the exact numbers rather than try to do this online -- on the phone. You could probably find it in the swimmers plot because it's separated there by dose and by indication.

Okay. So then one quick clarification. Before discontinuations that are listed here, are some of these being carried over from the ASCO data set as well because there is an intermingling of 2 patient data sets here.

If I understand correctly, this is -- your question is whether this includes the patients from ASCO. And the answer is, yes, it does include the patients from ASCO.

Our next question comes from Mike Ulz with Baird.

Maybe just a follow-up on some of the earlier questions. Just compared to the ASCO update, it looks like you had 3 additional PRs. Can you just clarify what dose and whether they were ovarian or lung? And then I have a follow-up.

Dirk, can you answer that question?

Yes. Yes. So by now, we have 6 PRs altogether on this dose escalation study. And there was 1 PR on the 20-milligram dose. There were 3 PRs on the 30-milligram dose cohort and there are 2 PRs on the 43-milligram dose cohort. And we -- so 1 -- 5 of those PRs were in ovarian cancer and 1 PR was in the NSCLC adenocarcinoma group. And remember, the adenocarcinoma group is smaller, but we definitely see activity in both of those indications.

And for the non-small cell lung cancer responder, what -- can you just tell us what the dose was for that patient?

Yes, that was the 43-milligram per square meter.

Got it. And then maybe just 1 last question for me. Just a follow-up on the biomarker data. It looks like you're kind of trending towards a cutoff of 110, but you want to do some follow-up work in your expansion cohorts. But just curious, could you be in a position where you have a different cutoff for ovarian versus non-small cell lung, for example?

I don't think we have enough information at this point to make a statement one way or another. But maybe Dirk has any additional comments.

Yes. So the expansion study actually will be very crucial to address that question because that study is designed in a way to explore NaPi2b expression at different ranges, from low all the way up to higher doses. We're going to have a sufficient amount of patients included here that will allow us to make those determinations. You're right. At the moment, what we see is that there is most likely a correlation between higher NaPi2b expression that goes along with activity. Whether that is similar or different between ovarian cancer and NSCLC, we can't tell at the moment, but that is certainly a question that we will address in the context of the expansion study that's ongoing.

Our next question comes from Boris Peaker with Cowen.

Great. Just following up on some of the prior questions. Can you comment on what is the median duration of response and how that correlates with NaPi2b expression?

Dirk, could you take that question? I think what we've shown is the duration of treatment, which is shown on one of the slides. Dirk, can you answer the question?

Yes. Yes. So at the moment, the data that we have are represented on Slide 18, which is the one with the duration on treatment. That slide shows you all the PRs. It also shows the distinction between NSCLC and the ovarian cancer patients, and the ones that are still ongoing. So we see good durability in terms of treatment duration in the number of patients. And as Dr. Richardson pointed out, in those patients with higher NaPi2b expression, the range or the amount of proportion of patients going out 16 weeks and longer with treatment is about 40%, which is remarkable, if you think about the patient population being so heavily pretreated and basically have run out of options with respect to their treatment.

No, I'm just looking at this without measuring every one of the swimmers plot. It just looks like it's roughly around 8 to 10 or so weeks as the duration of response and it looks somewhat similar between higher NaPi2b and lower just visually. That's why I just want to know if you have a quantitative number for that?

Yes, we don't have a number for that at this moment in time. Again, this evaluation is ongoing. And we would present that at a later point in time in the publication, but we are not in the position to do this right now because it's still ongoing evaluation.

And maybe a question for Dr. Richardson. My last question is, based on the data to date, what do you think you'd have to show in the pivotal study in terms of response rate, specifically in addition to durability of response for the FDA to accept a single-arm path to approval?

So I think -- thanks for that question. I think my understanding at least with other drugs that are looking at single-arm for accelerated approval. If we set the expected response rate, which -- it would be different than what we're enrolling, just to be clear in the escalation, what we'll be talking about as more of the expansion phase patients. So 1 to 3 priors would be the average. And the response rate in most of the previously published clinical trials are 12% for the control arm. So we want a response rate with a 95% confidence interval that excludes 12%. So you're looking probably in the 25% range or so.

Our next question comes from Daniel Wolle with JP Morgan.

This is Daniel for Jessica Fye. Question -- the first question is what can you make at the lack of response and durability for the 36-milligram per meter square dose compared to the 43?

Yes. Thanks for asking the question. I think when we -- if you look at the data more closely, you'll see that the 36-milligram per meter squared had patients with very low and some that were almost 0 H-score. And I think we attribute that to the lack toward the very low expression of the antigen.

Okay. And then maybe one more question for Anna. Are you also reiterating the timelines for reading out the full expansion cohort in the second half?

Yes. So Daniel, we all live in a very uncertain world, as you know. I think we're in a position to say we have a meaningful number of patients on the expansion cohort today that we can make a disclosure in Q2. I think we'll be able to be in a better position in the next few months to really confirm what the second half of the year milestones will be. It would be premature for me to do that given the uncertainty we all live in.

Got it. And one more, if I can ask. Were the responses at the 43-milligram per meter squared confirmed responses?

All of the responses we have presented are all confirmed.

Our next question comes from David Nierengarten with Wedbush.

One question and follow-up. First off, on the safety side, there were 3 patients who discontinued 1 before the scan. Could you maybe elaborate a little bit on that -- those patients dispositions? And then on lung cancer. I mean it looks, you had 1 PR on the swimmers plot in the high expressing group. Is there any more enthusiasm to continue looking at high expressing lung cancer patients? Or are you going to really shift the focus to follow on compound or ADC?

So, I'll take the second question, and I'll ask Dirk to answer the first one. So we are continuing to recruit in the expansion cohort, the lung expansion cohort. As we've always said, our patient experience in ovarian was ahead of our experience in lung, but we are continuing to recruit in the lung expansion cohort as well. And in both cases, before we make a definitive decision on patient selection, we want more data on the cutoff of the H score. So we're continuing to execute on the plan we had laid out at the beginning of the year. Dirk, do you want to answer the question of the 3 patients who were excluded?

Sure. Yes. So we had those patients excluded because they withdrew consent very early in the study, before we were able to do the first scan. So this is a patient population heavily pretreated. It's not uncommon that this happens. And as you know, in clinical studies, the patients always have that option to withdraw consent without any further justification and it happens. They may have moved on. Some of them may have given up on treatment altogether. So we don't -- unfortunately, we don't have further information from those patients at the moment when they withdrew our consent.

Okay. So it wasn't -- just to be clear, it wasn't due to toxicity or adverse event?

No, not that we are aware of.

[Operator Instructions] Our next question is from Tom Shrader with BTIG.

It's really a very general question. But -- Dr. Richardson, does the drug get harder to use above 30 milligrams? And does the company -- are you really confident you have a dose response over 30 mg, I mean, outside of 1 PR at 43. It's hard to convince yourself. So with the lowest effective dose sense, is 30 the best dose right now? Or just your thoughts.

I feel -- I've treated patients on -- I participated in this dose escalation, so I've treated patients at all the different dose levels. And I don't see a big difference clinically for my patients at 30, 36, 43. So we want to give the correct dose. That's always a little bit hard to define, but we want to give the dose that patients can tolerate that also has the highest chance of getting a response and also keeping that response as durable as possible.

Okay. So just for the company, do you feel like you need more doses at 36 and 40 to really go forward?

So, Tom, if you recall, we started the expansion cohort at 36. And as we got more experience at 43, we're now recruiting patients at 43. We saw our first response at 20. We saw additional responses at 30. So I think with the expansion cohort and the data we are collecting there, will give us a good sense of what the right dose is to go forward into pivotal studies. And we do think that it's important that we understand the right dose and make the right dosage selection as well as the right H-score cutoff as we move into a pivotal study. But we'll have a lot more data from the expansion cohort to make that decision. But we do feel there's a dose response. It's a bit hard to discern from the dose escalation because we are dealing with multiple variables. There's dose, there's H-score, there's lines of therapy. And I think the various variables might confound a little bit the -- what you would have seen otherwise, if you only had one variable, the dose -- in a dose escalation.

Our last question is from Debjit Chattopadhyay with H.C. Wainwright.

So the correlation with NaPi2b expression. These are obviously in very heavily pretreated patients. So as you move towards a more homogeneous population, would you not expect responses even in the intermediate dose cohort, I mean, intermediate expression?

Debjit, I think that we'll have to let the data take us, answer that question. And remember, on the expansion cohort, we're collecting both archival and fresh tissue, and we'll better understand what the cutoff is.

And one last one. In terms of the homogeneity of expression of NaPi2b, any thoughts or correlations with -- across different sites, I mean, for example, different metastatic sites?

We have done some work on that. And based on the data we have, there appears to be good correlation, and we are gathering more data as we speak, so we can increase our experience. But there appears to be good correlation between different -- the metastatic side as well as the initial tumor.

And I'm not showing any further questions. I would like to turn the call back to Anna Protopapas for her final thoughts.

So I wanted to maybe close by thanking everyone for joining us today. We appreciate the time you have taken, your continued support. And we look forward to giving you our next update on 1536 in the next few months. Thank you very much.

And thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for participating, and you may now disconnect.