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

Good morning and welcome to Mersana Therapeutics 2021 Virtual Analyst and Investor Day. [Operator Instructions] I would like now to turn the call over to Sarah Carmody, Executive Director, Investor Relations and Corporate Communications. Please proceed.

Good morning, and welcome to our first-ever analyst and investor day event. This morning, we issued a press release providing an update on XMT-1536 as well as our goals and anticipated milestones for 2021. Through -- 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. Please note that there is a dial-in phone number for investors and analysts who plan to ask the question that was provided this morning in the press release. 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 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 are early encouraging clinical and 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; that the development and identification of the company's product candidates and new platforms will take longer and/or cost more than planned; that the design, progression and timing of the company's clinical trials may not proceed as anticipated; and that our cash on hand might not be sufficient for our anticipated operating plan commitments. 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-19 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 of and 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, quarantine, 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. And with that, I'll turn the call over to Anna Protopapas, Mersana's President and Chief Executive Officer, for opening remarks.

Thank you, Sarah. Good morning, everyone. And thank you for joining us for today's strategic update. This is a very exciting event for us as we have a lot to share with you on both XMT-1536 and the rest of the pipeline. Today, we will showcase the progress we have made in 2020 and outline our plans and expectations for 2021. Joining us today is Dr. Debra Richardson, Associate Professor and Section Chief of Gynecological Oncology at the Oklahoma University Health Stephenson Cancer Center and the Sarah Cannon Research Institute in Nashville, Tennessee. Dr. Richardson will provide an update on the XMT-1536 ovarian cancer expansion cohort. Dr. Richardson is a key investigator, Chair of our Safety Review Committee and has extensive experience treating patients with XMT-1536. Also joining me today with prepared remarks is Arvin Yang, Chief Medical Officer, who will discuss our FDA interactions and our single-arm registration strategy; Brian DeSchuytner, Senior VP of Finance and Product Strategy will discuss areas of unmet medical need in ovarian cancer and our life cycle management plans; and Tim Lowinger, Chief Science and Technology Officer will introduce XMT-1660, our first-in-class B7-H4 ADC. Two other members of our executive team will be available for the Q&A section. Chuck Miller, our Senior VP of Regulatory Affairs; and Michael Kaufman, our Chief Manufacturing Officer. I will conclude the presentation with the outline of our anticipated goals and milestones for 2021; a year that has the potential to be as transformative for Mersana as 2020 was. Before we start, I wanted to formally introduce Arvin, who joined us in late November as our Chief Medical Officer. Arvin's depth and breadth of experience combined with his leadership skills will be invaluable to Mersana's next stage of growth. Welcome, Arvin. We are very excited to have you on board. 2020 was truly a remarkable year for Mersana. First and foremost, let me start with XMT-1536. We completed the dose escalation, established the maximum tolerated dose and demonstrated robust proof-of-concept in an expansion cohort of heavily pretreated patients with ovarian cancer. We have had 3 data disclosures demonstrating the potential for a robust and consistent level of efficacy and a tolerability profile without the severe neutropenia, neuropathy and ocular toxicity seen with some other ADCs. Today, you will see yet another update of this data from the ovarian cancer expansion cohort. We were granted Fast Track designation and had a successful FDA meeting that informed our plans to initiate a single-arm registration strategy, which we will outline for you in today's presentation. Second, we have observed early signs of activity with XMT-1536 in lung adenocarcinoma that supports the role of NaPi2b in this patient group and continue to work to increase enrollment and gain further patient experience in this indication. Third, XMT-1592 entered the clinic and is advancing through the dose-escalation portion of the Phase I study. Our objective is to clinically validate the potential differentiation that we observed preclinically. This is not -- this not only provides a second shot on goal for NaPi2b expressing lung adenocarcinoma patients but also informs platform selection for our future pipeline. Fourth, we have advanced our 2 first-in-class ADCs addressing areas of high unmet medical need into IND-enabling studies. Today, Tim will provide the exciting preclinical data generated to date on XMT-1660 our first-in-class B7-H4 ADC. On November 16 at the Immunosynthen webinar, we disclosed data supporting the unique potential of STING-Agonist ADCs to harness the power of the innate immune system to address significant unmet medical needs. We also shared data supporting the selection of XMT-2056, our first Immunosynthen ADC. We have also made significant progress in expanding our leadership team and strengthening our capabilities, positioning us well to continue to execute on our goals. Lastly, from a corporate standpoint, we have strengthened our balance sheet and are starting 2021 with approximately $255 million in cash, funding our anticipated operating plan for at least the next 2 years. We also have the ability to draw additional funds from our line of credit. This a truly remarkable year despite the disruptions brought about by the pandemic, Mersana's employees have remained focused on executing on our goal. Their dedication to advancing science and improving outcomes for patients is unparalleled. Let me move on to 2021, which we anticipate will be just as exciting for Mersana. There are 5 pillars to our strategy that will drive the next stage of Mersana's transformation. XMT-1536 in ovarian cancer is at the center of our strategy, as you will hear today. We will be launching a single-arm registration study early in the year followed later in the year by life cycle management studies aimed at exploring the potential of XMT-1536 as a foundational therapy for ovarian cancer patients. XMT-1536 and XMT-1592 in lung adenocarcinoma provide the second and third strategic pillars. We will seek to establish proof-of-concept for XMT 1536, and together with the clinical data we are generating in parallel with XMT-1592, we will aim to make a decision on the path forward in this indication with high unmet medical need. Two things to note, first, we are encouraged with the preliminary data from the early dose levels of XMT-1592. Second, the percentage of lung adenocarcinoma patients who are NaPi2b high appears to be around 40% compared to the 65% to 70% we observed in ovarian cancer, indicating that we will need to fully enroll our expansion cohort to get sufficient understanding of both the cut-off and the profile of the agent. XMT-1660, our first-in-class B7-H4 ADC should allow us to leverage a differentiated platform to advance our next molecule into the clinic. We believe that the significant learnings to date on our platform will allow us to advance this molecule forward in a streamlined fashion. And expect to submit an IND in Q1 of 2022. Lastly, we believe that our Immunosynthen platform based on the clinical data, we have the potential to stimulate the innate immune system in a tumor-targeted manner without the systemic liabilities of other approaches. Potentially, a game changer. XMT-2056, our first Immunosynthen STING-Agonist ADC, and we expect to advance it into the clinic in early 2022 with the objective of establishing proof-of-concept for our approach and informing our deep pipeline of other Immunosynthen candidates. With a promising pipeline, an experienced team and a strong balance sheet, we believe we are well positioned to execute on this strategy with the objective of making a meaningful difference for people living with cancer. Now it's my pleasure to introduce XMT-1536 new name, upifitamab rilsodotin or UpRi for short. Over the past year, data that -- from the ongoing Phase I study of UpRi has continued to suggest the potential for robust activity in late-stage platinum-resistant ovarian cancer patients, including patients who have been sourced with bevacizumab and PARP inhibitors. We have also been encouraged by the tolerability data and have not observed the severe neutropenia, peripheral neuropathy and ocular toxicities associated with some other ADCs. The NaPi2b biomarker may provide the potential for patient selection and enhance patient outcomes. The data set Dr. Richardson will share with you today continues to be consistent and further supports the potential of UpRi to help address the unmet medical needs of ovarian cancer patients. The planned single-arm registration study will be our first opportunity to bring UpRi to platinum-resistant patients who have such a high unmet medical need. However, we believe that the efficacy and tolerability data for UpRi to date indicates that it has the potential to play an important role in earlier lines of therapy, both as a single agent and in combination. Our plan is to expand our evaluation of UpRi in this earlier stage patients with the aspiration to establish UpRi as a foundational therapy in ovarian cancer. With that, I will turn over the call to Arvin, who will describe our single-arm registration approach, a strategy we have named UPLIFT.

Thank you, Anna. Before I start, let me first say that I'm excited to be joining Mersana and look forward to the opportunity to be part of this next stage of Mersana's evolution. The design of UPLIFT, our planned single-arm registration strategy is informed by the FDA feedback we have received. The discussion centered on the high unmet need population to be enrolled and the performance of the current standard of care in this population. The feedback also included the design of the single-arm strategy and the primary and secondary endpoints as well as the evaluation of the biomarker strategy. Our FDA interaction was positive and constructive, and we believe we have good alignment on the path forward for UpRi in platinum-resistant ovarian cancer. The platinum-resistant ovarian cancer population represents an area of high unmet medical need as evidenced by the Fast Track designation we received last year. Single-arm studies can be a path to registration acceptable to the FDA for populations with high unmet need. However, in order to assess the performance of a single-arm registration strategy, alignment is required on the performance of the standard of care. We have agreed with the FDA that these 3 contemporary studies are the best current benchmarks for the performance of the standard of care, consistently demonstrating an overall response rate of no more than 12%. It's important to emphasize that our expansion cohorts enrolls a more heavily pretreated population with up to 4 lines of therapy, with a significantly larger proportion of patients who have received prior PARP and bevacizumab treatment. Based on alignment with the FDA, we have defined a target population of the UPLIFT cohort that reflects patients with high unmet medical need. UPLIFT will be enrolling platinum-resistant patients who have received up to 4 lines of therapy. It's important to note that this population is more heavily pretreated population and the study is defining the performance of the standard of care but is consistent with the population in the expansion cohort, where we are seeing data supporting the potential for robust activity. Note that platinum-resistant patients who received up to 2 lines of therapy but are bevacizumab naive will be excluded from the UPLIFT cohort, but broader bevacizumab pretreatment requirements are not necessary for patients with 3 and 4 lines of therapy, consistent with the bevacizumab label. This is an important differentiator. This will allow us to explore the potential of UpRi to address the unmet medical need of patients who have not been previously treated with bevacizumab. Because we have not observed severe peripheral neuropathy on UpRi, we do not plan to exclude patients with baseline neuropathy. These patients are also included in the expansion cohort. This is potentially an important differentiator because platinum-resistant patients have received multiple courses of platinum and taxane, and often experience long-term detrimental effects associated with neuropathy caused by these agents. Patients will also not be biomarker selected, but the role of the biomarker will be evaluated. Specifically, the primary endpoint for the UPLIFT cohort will be ORR in the higher NaPi2b population. The key secondary endpoints will be the ORR in the overall population. This cohort is designed to allow us to more fully evaluate the role of the biomarker to enhance patient outcomes. Enrolling patients without waiting for a biomarker result is also an important differentiator that we believe will contribute to speed of enrollment. Secondary endpoints will include duration of response and safety in both the higher NaPi2b and the overall population. Consistent with precedent, the FDA indicated that the performance of the single-arm cohort will be evaluated based on the 95% confidence interval of the objective response rate as well as the totality of the data, including the secondary endpoints of duration response and safety and tolerability in order to determine risk/benefit. The efficacy will be evaluated in the higher NaPi2b population, which defines the primary endpoint population as well as the overall population, which defines the secondary endpoint population. We expect to enroll approximately 180 patients in the UPLIFT cohort, of which at least 100 are expected to be the higher NaPi2b to achieve the physical power necessary to conclusively exclude the performance of the standard of care. The FDA has agreed to our plan to initiate the UPLIFT cohort as an amendment to the current protocol. This provides for significant operational efficiencies, and we anticipate will help ensure continued enrollment momentum. On a site-by-site basis, upon approval of UPLIFT amendment by each site, enrollment will shift from the expansion cohort to the UPLIFT cohort. Data between the expansion cohort and UPLIFT will be clearly segregated in the database for separate analysis. Patients enrollment in an expansion cohort will not be part of the UPLIFT cohort for the reasons I'll now explain. The 2 cohorts in our study are designed to ensure a systematic evaluation of the potential of patient selection to enhance patient outcomes. As you are aware, in the current expansion cohort, we are evaluating expression based on our clinical assay. This is an assay run in a single lab by a single partner. At this point, we have over 70 patients enrolled into the expansion cohort and expect by the time we switch sites to the UPLIFT cohort to have more patients enrolled given the high level of interest in study participation by the investigators. With our diagnostic partner, we plan to repeat the evaluation of the expression in these expansion cohort patients using our planned commercial assay as it means to train that assay in order to produce a highly reproducible assay, a critical component to the potential success of UPLIFT. Remember that the proposed commercial assay would eventually be deployed in a variety of hospitals in clinical settings so it's critical that it's reproducible. This commercial assay, trained by the data set from the expansion cohort will be used in a prospectively defined retrospective analysis of UPLIFT. This approach should allow for the evaluation of both the higher NaPi2b and the overall population. And based on the results, we expect to deploy either a companion diagnostic or a complementary diagnostic depending on which strategy we think will be most beneficial to patients as well as feedback from the regulators. In conclusion, with this constructive input from the FDA, we are well on our way to finalizing the amendment to the protocol for the UPLIFT cohort and expect to initiate patient dosing this quarter. We believe the design of UPLIFT provides potential for significant advantages. First, given this is an amendment, it will accelerate the ability to initiate the cohort. Second, it includes a broad patient group with high unmet medical need. Consistent with the heavily pretreated patients that benefited from UpRi in our expansion cohort. Specifically, it includes patients who are platinum-resistant and have received up to 4 lines of therapy in contrast to other studies that are limited to patients with up to 3 lines of therapy. In addition, patients with 3 to 4 lines of therapy are not required to have bevacizumab pretreatment. Third, it incorporates development and validation of a planned commercial assay based on a training data set from the expansion cohort to assess the role of the biomarker and patient selection in impacting patient outcomes. With that, I'll pass it to Dr. Debra Richardson, who will provide an update on the ongoing expansion cohort.

Thank you, and good morning, everyone. I am very pleased to be able to join today to provide an update on the ovarian cancer cohort of the expansion portion of the XMT-1536 Phase I study. Before I begin, I'd like to thank the patients and their families participating in this study as well as acknowledge my fellow investigators, their research staff, and the U.S. and international ovarian cooperative groups for their work on advancing this promising investigational therapy for patients with ovarian cancer, a population with continued significant unmet medical need. I'll start with a brief reminder of the expansion study design. While 2 cohorts are being enrolled into this expansion study, namely ovarian cancer and non-small cell lung cancer adenocarcinoma, we will focus today on the ovarian cancer cohort. The ovarian cancer cohort includes patients with high-grade platinum-resistant serous ovarian cancer with 1 to 3 prior lines of therapy. Unlike some other studies in this space, we also include more heavily pretreated patients with 4 previous lines of therapy. These patients may also be platinum-resistant or refractory or they may be very difficult-to-treat patients that have not had platinum as a recent prior line due to toxicity or intolerability. Doses of 36 milligrams per meter squared and 43 milligram per meter squared administered intravenously every 4 weeks are presented here today. The majority of patients were treated with 43 milligrams per meter squared, following an amendment in December 2019. Patients are not selected for NaPi2b expression. However, archived tissue to biopsies are collected for retrospective assessment of NaPi2b expression. This slide outlines the patient demographics and disease characteristics as of the data cutoff of December 3, 2020. 72 patients with ovarian cancer were included in the analysis with a median age of 68 years. The majority were ECOG 1 status, ambulatory but with physical limitations from their disease. 35% had 4 or more prior lines of therapy and 90% were platinum-resistant or refractory to their most recent line of platinum-containing chemotherapy. The majority of patients have received prior bevacizumab and/or PARP inhibitors. This is a population with a very significant unmet need, having failed all available therapy and with an expected median overall survival of less than 1 year. 15% of patients harbored mutations in BRCA 1 or 2. As I mentioned, NaPi2b expression is being evaluated by IHC in the archive and where available in fresh tumor tissue, and the correlation between biomarker expression and clinical response is being explored as part of a diagnostic development. The population has been bifurcated by lower and higher NaPi2b expression levels based on the lowest NaPi2b expression level at which a response was observed with dose escalation. This is consistent with Mersana's previous disclosure of expansion data at SGO, ASCO and ESMO. Expression levels are not yet available for all patients, but note that about 70% of patients with a known NaPi2b status are characterized as higher NaPi2b. Turning to safety. With further follow-up, XMT-1536 tolerability data were similar to previous data releases with no severe neutropenia, peripheral neuropathy or ocular toxicity that can be observed for other ADC. The most frequently reported treatment-related AEs included generally Grade 1 and 2 fatigue, nausea and transient isolated 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 test, generally peaking on day 8 and recovering by the next dose. Thrombocytopenia is also transient in nature, generally nadiring at day 8 and recovering prior to the next dose. 31% of patients experienced dose delays or reduction or discontinuations due to treatment-related AEs. As you will see in the coming slides, despite those reduction, some of the patients achieved or deepened their responses while on a reduced dose of 30 or even 20 milligrams per meter squared. As an oncologist, being able to dose reduce and retain clinical activity is an important potential feature of XMT-1536 for patients living with metastatic cancer. With additional follow-up of these heavily pretreated patients, we would expect more serious adverse events as some patients may experience adverse events associated with disease progression. The SAEs were generally consistent with the known adverse event profile. A total of 28 patients have reported SAEs, 2 patients with ovarian cancer. 11 patients reported treatment-related SAEs. Since the ESMO data cut, new treatment-related SAE cases include abdominal pain, pyrexia, renal impairment and fatigue. Of note, 2 cases of pneumonitis are reported. A Grade 2 pneumonitis, which was previously reported at ASCO and newly reported in this disclosure is a Grade 5 pneumonitis assessed by the investigator as probably related to drug. Unfortunately, these types of events happen in studies of patients living with late-stage cancer. Let me give you some more color on this patient with Grade 5 pneumonitis. This was an 87-year old patient with recurrent ovarian cancer who previously received 4 prior lines of therapy. She developed dyspnea after 2 cycles of XMT-1536 and was initially treated empirically for an alternative diagnosis in a local hospital. 10 days after her initial symptoms, she was diagnosed and treated for pneumonitis at the cancer center. Ultimately, due to family preference, she was transitioned to comfort care and unfortunately died. Upon learning of this event, the Safety Review Committee, which I chair, assembled to evaluate the case. Assessment of the cumulative experience for potential other pneumonitis cases was conducted. Out of 145 patients treated across dose escalation and expansion at the time, 8 additional patients were identified. The majority of these cases were Grade 1 or Grade 2 in severity. Cases generally appear to improve or resolve with dose delays, reductions and treatment with steroids. Modifications to protocols were made to enhance identification and management of pneumonitis as well as dose delay and reduction guideline. This event and the proposed protocol changes were submitted to the FDA, and no further recommendations have been received. Patients enrolled at my site represent 3 of the 9 cases described above. My experience has been that pneumonitis is reversible with dose delay and discontinuation and response to the treatment with steroids as needed. We have also now treated over 150 patients in the Phase I study and continue to be encouraged with the safety data to date XMT-1536. Turning now from safety to efficacy data. These data continue to show that XMT-1536 is active in ovarian cancer and has the potential to provide patients with clinically meaningful outcomes. Of the 72 patients with ovarian cancer, 47 were evaluable for RECIST response with at least 1 scan. In the 47 patients with ovarian cancer, we observed 2 complete responses as was reported at ASCO and ESMO and 11 partial responses. All responses reported here are confirmed. In the overall population, the objective response rate was 28% and the disease control rate was 68%, which, in part, reflects the changing proportions of higher NaPi2b and lower in each data cut as the study is still in progress. As a reminder, both patients with confirmed complete responses and most responders had prior treatment with bevacizumab and PARP inhibitors. The objective response rate is 32% in the higher NaPi2b population, which is consistent with our previous reported response rate at ESMO in 20 patients. With increasing follow-up and additional patients, we begin to see the potential enhancement of activity offered through an NaPi2b biomarker selection strategy. The higher NaPi2b population, which is 66% of the population, includes both patients with complete responses, which are very uncommon in this setting and in partial responses. In addition to a 32% objective response rate, additional patients are also potentially benefiting with 74% of disease control rate. Yet, we continue to see activity in the lower Napi2b population with an objective response rate of 15% and a disease control rate of 54%. While we will establish the biomarker cutoff and declare the patient selection strategy based on the totality of the data, it appears that lower NaPi2b expression level in a tumor sample does not preclude benefit from XMT-1536 in some patients. These data continue to demonstrate promising activity and the potential of XMT-1536 to provide a clinically meaningful benefit for patients with platinum-resistant ovarian cancer particularly in the most difficult-to-treat patients with few other options. The waterfall plot shows the change in tumor dimensions of the target lesions for individual patients as characterized by NaPi2b expression and those where expression is not yet determined. The emerging profile of XMT-1536 continues to show activity with deep responses, including complete resolution of target lesions. In addition, 67% of patients had a reduction in target lesions, including the majority of patients with stable disease, demonstrating tumor shrinkage. Approximately half of the patients had bulky disease at the time of study entry, including the patient at the far right of the waterfall plot, with target lesions measuring over 5 centimeters each that showed 100% resolution after 2 cycles of XMT-1536, further supporting the notion that XMT-1536 may be a potent anticancer therapy in patients with heavily pretreated and high disease burden ovarian cancer. On this side of the graph, we observed 69% of responders obtaining a response by the first scan or end of cycle 2 and multiple patients who have shown deepening response over time. An important note, all of these reported responses were confirmed by successive scans showing continued shrinkage of tumor lesions by more than 30% as required by RECIST 1.1. The tumor blot is broken out by higher, lower and not yet determined NaPi2b expression. As you can see, there is a trend towards longer time on study in the higher NaPi2b expression group, including a patient up to 1 year. The group with NaPi2b expression not yet determined has generally only recently entered the study. Additional follow-up as of the data cut, the median duration of response in the higher NaPi2b population was around 5 months with 10 patients evaluable. With the response occurring on the first and at months 2 for 70% of patients and at month 4 for the balance, these responding patients were able to delay the worsening of their disease for a median of between 7 and 9 months, a significant benefit for group of patients within the expected overall survival of less than 1 year. In conclusion, XMT-1536 continues to show similar tolerability to previous data cuts with no severe neutropenia, peripheral neuropathy or ocular toxicity. Encouraging antitumor activity continues to be observed in patients with ovarian cancer, with an objective response rate of 32% and a disease control rate of 74% in the higher NaPi2b patients. The majority of responses occurred by the first scan and the median duration of response in this population is approximately 5 months with the median duration of disease control for the responders of approximately 7 months, suggesting the potential to provide a clinically meaningful benefit in a population that faces an objective response rate of 4% to 12% and expected overall survival of less than a year from the single-agent chemotherapy standard of care. Responses are observed in those failing platinum and previously treated with bevacizumab and PARP inhibitor. These data further support the continued development of XMT-1536 for the treatment of platinum-resistant ovarian cancer with poor prognosis and very limited treatment options. Informed by the FDA meeting, we plan to operationalize the single-arm UPLIFT cohort as an amendment to the ongoing study, capitalizing on enrollment momentum, the existing relationships with the GOG and ENGOT and the Fast Track designation received earlier this year. As Arvin indicated, discussions with the FDA, which I attended, were constructive and the path forward with UPLIFT is clear and streamlined. I will now turn the call over to Brian.

Thank you, Dr. Richardson, for your leadership with the Phase I study and for sharing with us your deep experience treating patients with UpRi. We've outlined what we believe is a clear path to the market in platinum-resistant ovarian cancer. While UPLIFT aims to demonstrate the potential of UpRi to help a group of patients with a very severe unmet need, this is only one of the many unmet medical needs in ovarian cancer and only one of several settings in which UpRi may offer benefit for patients. Innovation in ovarian cancer has been limited until now with bevacizumab and PARP inhibitors being the only targeted therapies introduced in the past decade. These agents were first introduced in the platinum-resistant setting and in late lines of therapy. However, recent changes in the treatment landscape with the approval of bevacizumab and PARP inhibitors in recurrent platinum-sensitive patients and more recently in frontline, have created new unmet needs. Specifically, earlier use of bevacizumab and PARP inhibitors creates opportunities to help patients who exhaust these options early in treatment. In the future, many recurrent platinum-sensitive patients may have already received bevacizumab or PARP inhibitors or both in combination by the second or third line of therapy. The increasing use of maintenance with bevacizumab or PARP inhibitors creates both a definitional and a molecular challenge. Patients who relapse following maintenance treatment may have a platinum-free interval of more than 6 months, which is the definition of platinum-sensitive disease, but their tumors may have molecular differences that mean that they are less responsive to subsequent platinum therapy. This trend is supported by real-world evidence in pivotal study sub-analyses presented at ESMO 2020 that suggests prior part maintenance therapy may result in poor response to platinum in later lines. New non-platinum combinations and potentially new maintenance treatments are needed to serve this growing pool of PARP pretreated patients. Better tolerated and more efficacious platinum-based regimens are also needed for ovarian cancer patients as cumulative toxicities, particularly neuropathy and persistent cytopenia, can be burdensome and impact quality of life for patients. In addition, patients who are not definitionally platinum-resistant, but cannot tolerate platinum and thus are not candidates for platinum are also in need of better tolerated and more efficacious regimen. Finally, we have discussed the severe unmet need present in the platinum-resistant setting, where the single-agent chemotherapy standard of care delivers low response rates and less than 1 year of overall survival. Our life cycle management strategy aims to initiate studies to generate data in support of UpRi's profile in each of these settings. Platinum combinations, non-platinum combinations and maintenance in addition to UPLIFT. And as a reminder, a key potential attribute of UpRi is that the data to date have not shown cases of severe neutropenia, peripheral neuropathy or ocular toxicity. In a recently published Phase I study of the combination of platinum with lifastuzumab vedotin are now terminated NaPi2b targeted ADC based on the vcMMAE platform. The combination resulted in significant overlapping toxicities, and the program did not progress further. Data from the Phase I expansion study of UpRi have demonstrated activity without cases of severe neutropenia, peripheral neuropathy, potentially making it a suitable partner to platinum therapy. UpRi has also not shown the ocular toxicity of some other ADC platforms. Of note, our discussions with the FDA highlighted the FDA's focus on ocular toxicity, given the profile of ADCs in development as well as the recent approval of an ADC with this signal, having an important implication for patients and for treatment logistics. As Anna mentioned in the introduction, our objective is to explore the potential of UpRi to be a potentially foundational therapy in ovarian cancer. The UPLIFT cohort, a planned single-arm registration strategy, addressing patients with the highest unmet medical need, aims to deliver our first indication. The UPGRADE Umbrella study will evaluate combinability and will provide a platform for further studies in the platinum-sensitive setting. We expect to use the data generated in these and all other studies to plot a course into earlier lines of therapy. We will be providing more information on our life cycle management plans over the course of the year. I'll now turn it over to Tim to present XMT-1660, our next first-in-class ADC, targeting B7-H4.

Thank you, Brian. I'm very excited to share with you more details on our next DolaLock ADC. We believe that B7-H4 is a well-suited target for a DolaLock ADC, and let me explain why. First of all, B7-H4 is selectively expressed on tumor cells in multiple indications with unmet medical needs. Of course, that provides us the opportunity to target those tumor cells and selectively deliver the DolaLock payload. As you've heard before, our controlled bystander effect is designed to allow a controlled diffusion of our proprietary payload to neighboring tumor cells to affect so-called bystander killing. We also know, based on preclinical studies, that our DolaLock ADCs lead to immunogenic cell death in that our DolaLock payload can activate dendritic cells in the tumor, priming a potential immune response as well. These effects are analogous to what we see with NaPi2b as a target, but a differentiator B7-H4 is that it is also expressed on immunosuppressive tumor-associated macrophages, providing the opportunity to coapt those cells in a targeted manner to further contribute to both the cytotoxic and immunogenic effects and create what we clinically describe as a perfect storm in the tumor microenvironment. Because we often focus on the cytotoxic effects of ADCs, the data shown here is just a reminder of the nonclinical data we have generated to support that our DolaLock payload and ADCs can induce immunogenic cell death and contribute to an immune response. This is why there's growing interest in combining appropriate ADCs with checkpoint inhibitors, for example, which might be especially appropriate for our DolaLock ADC, given the favorable and differentiating tolerability profile we have seen to date. As for indications, as already mentioned, B7-H4 is selectively overexpressed in multiple tumor indications with high unmet medical need, including major indication such as triple-negative breast cancer and hormone-receptor-positive breast cancer as well as more niche indications, such as bile duct carcinoma. B7-H4 is a member of the B7 receptor family, which also includes PD-L1, which is also known as B7-H1. Interestingly, the expression of PD-L1 and B7-H4 appears to be almost mutually exclusive. Multiple reports, such as the breast cancer example shown here from Altan and coworkers, show that patient samples that expressed PD-L1 do not express B7-H4, whereas tumors that don't express PD-L1 do express B7-H4. This opens up very interesting possibilities for development. For example, patients who progress on or not candidates for PD-L1 therapy because of lack of PD-L1 expression, may be a readily identifiable population that may be appropriate for B7-H4 targeted therapy. We have stated multiple times that we don't believe ADCs are onetime fits all, and we strive to identify the optimal ADC for a given target in a data-driven manner. This slide reflects some of that effort. As you know, we have 2 DolaLock platforms, Dolaflexin and Dolasynthen. We use both of these clinical-stage platforms to create a variety of ADCs and tested them head-to-head to identify the optimal ADC for B7-H4. In the example here, we show 3 different DolaLock ADCs, all created with the same antibody. A site-specific Dolasynthen, DAR 2 ADC, shown in purple; a stochastic Dolaflexin DAR 12 ADC, shown in orange; and a site-specific DAR 6 Dolasynthen ADC, shown in blue. In 2 separate tumor models as shown here, all 3 ADCs were administered as a single injection into mice at an equivalent payload dose. What's also clear is that the DAR 6 ADC in blue clearly outperforms the other comparators. In fact, as shown in the model on the left with the dash blue line, the DAR 6 Dolasynthen ADC shows the same activity as the other comparators at a 50% lower payload dose. Or in other words, it's twice as potent as the other 2 ADCs. So based on these and multiple other preclinical studies, including additional efficacy and head-to-head tolerability studies, we have selected the Dolasynthen DAR 6 ADC as our clinical candidate, which is now called XMT-1660. Of course, it's not only efficacy that drives our decision, and we've extensively evaluated XMT-1660 preclinically. The PK profile shows our long half-life of circa 5 days in nonhuman primates as well as dose-dependent exposure, XMT-1660 was found to be well tolerated in nonhuman primates after multiple doses. And importantly, it demonstrates a positive therapeutic index based on well-tolerated exposure in nonhuman primates relative to efficacious exposures in mouse. So in summary, XMT-1660 represents a first-in-class opportunity with a target that is especially well matched to the potential benefits of our Dolasynthen platform, an opportunity to address multiple indications with high unmet medical needs, and is an ADC that has been precisely designed and selected to maximize its potential. We're very excited to move this forward into the clinic as efficiently as possible. And with that, I'll turn it back to Anna.

Thank you, Tim. The data that Tim shared with you on XMT-1660 highlights the power of our highly differentiated approach that allows us to optimize ADC properties on a target by target basis. I believe this is a unique capability in the ADC field. In today's presentation with an update to the UpRi expansion corporate data, we have continued to demonstrate robust activity in heavily pretreated patients without the severe neutropenia, neuropathy or ocular toxicity seen with other ADCs. This data set supports our investment in advancing UpRi into the UPLIFT cohort. The UPLIFT cohort is designed to be operationally streamlined, support the development and validation of a commercial diagnostic and exploring in a systematic manner, the role of patient selection in outcomes. Lastly, there remains significant unmet medical need in the earlier lines of ovarian cancer, and the efficacy and tolerability data to date supports further exploration of UpRi in earlier lines of treatment. As we have outlined in this presentation, our vision is to build UpRi into a potential foundational therapy in ovarian cancer by moving into platinum-sensitive disease with opportunities both as treatment and as maintenance therapy, both as a single agent and in combination. To date, the absence of severe neutropenia, peripheral neuropathy and ocular toxicity is encouraging as is the activity in bevacizumab and PARP inhibitor pretreated patients. Together, this provides the potential to improve care for patients waiting for new options. Lastly, I would like to close our update today with a review of our anticipated goals and milestones for 2021. I'll start with UpRi and recap what we heard today. First, we expect to initiate the planned UPLIFT single-arm registration strategy in the first quarter of 2021. As for our longer-term life cycle management studies for UpRi in ovarian cancer, our goal is to initiate the dose-escalation portion of the UPGRADE study, starting with a combination study with platinum in Q3. And lastly, for UpRi, we expect to have a meaningful number of lung cancer patients enrolled in the expansion study and be able to provide a data update from that cohort in the second half of 2021. Moving to XMT-1592. Though we did not have time today to discuss XMT-1592, our Dolasynthen ADC targeting NaPi2b, we are pleased to say the dose-escalation portion of the Phase I study is moving forward as planned. We are encouraged by the data from the early dose cohorts. We plan to disclose dose escalation data in the second half of 2021. As we have said in the past, our objective is to compare the XMT-1536 lung adenocarcinoma expansion data with the XMT-1592 data to make decisions as to which molecule we will take forward. As such, we expect to be able to outline our further development plans for XMT-1592 in the fourth quarter of 2021. For XMT-1660, as Tim said earlier, we plan to complete IND-enabling studies in 2021 and initiate a Phase I dose-escalation study in early 2022. Lastly, for our early-stage ADC programs, we introduced to you XMT-2056, our first STING-Agonist ADC for Immunosynthen platform back in November. In the fourth quarter of 2021, we plan to complete IND-enabling studies and disclose our target. We plan to initiate the Phase I dose-escalation study in early 2022. Finally, we will continue to leverage our proprietary platforms and continue to expand our pipeline of innovative ADC candidates while proactively evaluating potential collaboration for current and future programs. We are leveraging our innovative and differentiated platforms to build a pipeline of medicines that are designed to help cancer patients in need. In 2020, we have made significant progress in advancing this pipeline. In 2021, we have the potential to make further significant strides as we launch UPLIFT and UPGRADE for UpRi, advance our understanding of NaPi2b expression in lung adenocarcinoma patients and select our lead asset for this indication and advance XMT-1660 and XMT-2056 through IND-enabling studies. With that, I will turn it over to the operator for Q&A.

[Operator Instructions] Our first question comes from the line of Mr. Jonathan Chang.

First question, can you provide any color around the time lines for the UPLIFT cohort?

Thank you, Jonathan. This is Anna. At this point, we're going to refrain from providing an update on the time lines for UPLIFT other than to say that it will be initiated in Q1. As you know, we have -- as you can see from the expansion cohort, we have quite a bit of momentum on the expansion cohort trial. And this will be an amendment to that cohort. We have great support from the corporative groups, both here in the U.S. and in Europe. But because of the uncertainty brought about by COVID, we decided it was wiser to hold off before giving more precise guidance on the enrollment time line for UPLIFT. We will do that in due course. We will give guidance in due course. But at this point, we thought it was wise to hold off. We are though encouraged by the enrollment rate we showed in the expansion cohort by the number of sites that are engaged in the expansion cohort and by the excitement of investigators both here in Europe to participate in this study.

Got it. Second question, regarding your recent regulatory interactions, I'm curious to know if there was discussion around what the bar for duration of response is?

Yes. Maybe I'll ask Arvin to comment on that.

Yes. Thank you, Anna. And so thank you for the question, Jonathan. And so in relationship to the duration of response, we did discuss with FDA in relationship to the standards of care to define the objective response rate. As was described earlier, there's 3 Phase III studies that define that standard of care with this refractory population is at best 12%. But in discussions with FDA, as is typical it will be the totality of the information, including the response rate, the duration of response and the safety that will go into the determination of the benefit/risk.

Got it. And just last question for me. How should we be thinking about the implications of a pneumonitis observed on your development strategy? And is there a mechanistic explanation for this?

Yes. Maybe I can ask both Arvin and Dr. Richardson to comment on that. As you saw from the data, this is a low-frequency event and one that is readily manageable, but Dr. Richardson has the most experience with them.

Dr. Richardson, would you like to start and then I can certainly add on?

Sure. Thank you, Anna, and Arvin, and thanks for the question, Jonathan. My experience basically has been that the pneumonitis has typically been Grade 1 or 2 and in general has been reversible with dose delay and discontinuation and also response to steroids as needed. We've now treated over 150 patients, and we have 9 cases of the pneumonitis. And we did make some modifications to the protocol in order to enhance identification and management of the pneumonitis as well as dose delay and reduction guidelines. And these were reviewed, submitted to the FDA, no further recommendations were received. So I think that this is a manageable thing. And quite frankly, there are many other drugs that cause pneumonitis, and oncologists are relatively adept at recognizing the signs and being able to intervene. And I'll let Arvin answer.

Yes. Thank you, Dr. Richardson. I think the only thing I would add is that when evaluating the pneumonitis, to your point, I think you have to look at the totality of the safety information. And again, I think we've shown -- Dr. Richardson kindly showed that the safety profile does have consistency in relationship to, again, no evidence of the severe peripheral neuropathies, neutropenias or ocular toxicities that are potentially associated with other regimens. And so again, I think that affords them the potential for the combinability and utilization in studies in potentially different types of settings. Maybe just to pivot to your other point, though, from a preclinical perspective, it's unclear at this time, just really in relationship to whether or not it is associated with a sort of a target or a platform media type effect. What we do know is actually is that there is NaPi2b expression within pneumocytes. But in our preclinical toxicology experiments, we did not find evidence in relationship to toxicity associated with the lungs.

Our next question comes from the line of Mr. Tom Shrader.

Congratulations. To follow on the previous line, can you -- do you have enough pneumonitis signal to benchmark relative to other drugs like Daiichi's 8201? Is it significantly lower? Is it similar?

Arvin, can you comment on this?

Yes. Thank you, Tom. And so what I would say is that you have to really look at the 150 patients that we have and recognize that they are low grade in nature for the majority of them, as Dr. Richardson was outlining, right? So 7 of those cases out of the 9 are Grade 1, Grade 2. She's already pointed out that pneumonitis can be an adverse event, unfortunately, associated with multiple different classes of therapies. And you can see here that the frequency is lower. Again, the 9 of the 145 or plus treated per se. And they have been manageable, reversible. And so given the guidance that we have in the protocol, I think it will only further enhance the ability to not only identify but also manage these adverse events if they were to develop in the future.

Okay. Great. And second, safety. So did you give an overall neutropenia number? And I'd just be curious to Dr. Richardson's thoughts on trying to combine this drug with platinum. Does it seem reasonable still now that you have more data? And would fatigue probably be the big thing you'd be monitoring?

Thanks, Tom, for the question. I did miss the second part. I heard about the platinum, but something dropped off about what would you be concerned about combining with platinum, what side effect?

That was fatigue.

Fatigue, sorry. So I think that it can probably combine with platinum. Obviously, we need to do the trial to find that out. Thrombocytopenia is something we would have to monitor, but it has not led to dose delays in general, on this particular trial. So we would have to monitor for that in combination with platinum. And then in regards to fatigue, in general, we can manage the fatigue through various methods that we discuss with patients. And so I don't think that, that would be a major problem combining it with platinum. That would not be my primary concern.

Okay. And then one question. Why did you drop the 4 lines for platinum-sensitive patients from the pivotal trial?

Maybe, Arvin, I think -- would you like to answer that?

Sure. Thanks, Anna. I just want to make sure. And so just for clarity, I mean we -- in discussions in a very positive collaborative fashion with the FDA, really, we were working together to find again the highest area of unmet need, just in relationship to where the benchmarks would again be defined by those Phase III studies that define that 12%. And so the unmet need was in alignment with the discussions with the FDA.

Yes. And Tom, may I add that there was a handful of patients in the expansion cohorts that were not formally platinum resistant, but were fourth line or beyond. So it's a very small number of patients and -- that were in the expansion cohort.

Our next question comes from the line of Ms. Jessica Fye.

I was curious to know maybe a good amount of overlap here, but have you looked at the subgroup of your expansion cohort patients who would meet the UPLIFT enrollment criteria? And if so, can you tell us their ORR and DOR?

Anna, do you want to go ahead?

Go ahead, Arvin.

Yes. Yes, sure. Thanks, Jess, for the question. So just to give you a sense that the expansion cohort when applying the UPLIFT, it does have relative similarities in regards to activity. So we are seeing activity essentially regardless of line of therapy, whether they've been treated with bevacizumab or PARP inhibitor therapy. So it gives us confidence in relationship to as we move forward and plan and design of the UPLIFT population.

Okay. And given that the UPLIFT trial will enroll all-comers, what was the duration of response in the overall population in the expansion cohort? And related to that, maybe for Dr. Richardson, what would you want to see for a duration of response in the NaPi2b high? And what would you want to see in the overall population?

Maybe I'll handle that.

Yes, go ahead.

Sorry, go ahead. Dr. Richardson, do you want go ahead?

Sorry. I wasn't sure if you want me to respond. So thanks, Jessica, for the question. I mean, I think in regards to duration of response, we really need to, as Arvin had pointed out, look at the totality of the data and so it's not just duration of response, it's going to be response rate, duration of response and the safety and tolerability, which I think we've demonstrated pretty well at this point with about 150 patients treated. And so in general, most patients were having a response, either at the first scan or the second scan. And that's looking at a decent duration of response of 5 months or longer. And quite frankly, that's quite clinically meaningful to these patients who, on average, have a median overall survival of less than a year at this point.

The only thing I'll add on to that answer...

And what was the duration of response for the overall population?

Right. So I can answer that. And the only thing I would add is if you go back and you have the slides available to you, you will be able to see that we've shown not only the duration of response for the higher NaPi2b, and that's the 5 months and there's the 10 patients that are there, we also showed the patients' duration of response for the lower as well as the nondetectable in some bullets below. And again, they're very small numbers. And so in part, giving you an opportunity to understand both in the higher and lower based upon the sample sizes we have at the moment.

Okay. And maybe just to confirm lastly. Of the total 180 patients in UPLIFT, how many do you expect to be NaPi2b high? And can you just elaborate a little more on the motivation behind enrolling all expression levels? Is it to increase commercial opportunity, to speed up enrollment since you won't need to confirm expression in advance or is it because you haven't yet firmly established the NaPi2b cutoff?

Arvin, I think you can answer that question.

Yes. No, absolutely. Thank you. And so thank you for that question. Let me walk through them and start with actually the 180 patients. You've seen from the demographic slides and also independently from our tumor banks that we are seeing a prevalence of approximately 65% to 70% of the higher NaPi2b expressers within the overall population that we are bringing on to study or seen from the tumor banks. And so that affords us an ability with the 180 overall patients to essentially have projected around 100 patients or so in the higher NaPi2b population. And that essentially gives us -- and this is speaking to the second question, 2 shots on goal, right? And so this is essentially a single-arm study with an opportunity to not only evaluate objective response rate within a higher NaPi2b population, with sufficient patients to potentially support regulatory approval but also to support an overall indication with a potential complementary diagnostic to potentially identify patients that would have enriched opportunity for benefit. If we see that the benefit of -- and risk supports an indication within the overall population. So that hopefully speaks to your question just in regards to the strategic intent and relationship to the approach we're taking.

Our next question comes from the line of Mr. Boris Peaker.

Can you hear me? Just want to confirm.

Yes, we can. Go ahead.

We can.

Fantastic. So first question, in terms of clinical study design. I'm just curious, did the FDA request you conduct a randomized confirmatory trial in addition to the single-arm UPLIFT study?

As is typical with the FDA, there will be a requirement for a confirmatory study. I think the FDA has confirmed that there's only a need for 1 confirmatory study, and we will be talking about it as we finalize our plans around the confirmatory study. But at this point, it's premature to provide guidance on that.

Got you. And I just wanted to circle back on the pneumonitis question. Are there any predictive biomarker or any kind of criteria that you could -- selection criteria you could establish in a study to minimize or reduce overall severity or occurrence of pneumonitis?

I'm not familiar with any biomarkers to predict this, but I don't know if Arvin has any comments on this.

Yes. Thanks, Anna. You're absolutely right. So there are no biomarkers that are known, to my knowledge and relationship to preselecting or screening out essentially patients with pneumonitis or the potential for pneumonitis. However, what we have done in the protocol is to ensure that we're excluding patients that have had history of pneumonitis, which obviously is very rare, in order to screen for potential clinical factors.

Got you. And my last question, you mentioned that you're collecting some fresh tissue NaPi2b for sampling -- for the NaPi2b sampling. I'm just curious, do you have any data to show correlation between archival tissue NaPi2b expression versus fresh tissue NaPi2b expression?

So Boris, we've done a fair amount of work both in comparing fresh and archival tissue, but also looking at tissue banks, where we can compare primary and metastatic tissue, but overall, we see good concordance.

Our next question comes from the line of Mike Ulz.

Just a couple of questions on the UPLIFT study in terms of the design there. Looks like you guys are kind of giving yourself an opportunity to have a broader label, which includes sort of the low NaPi2b expressers as well. So I'm just curious, in terms of the endpoints and maybe the powering of the study, is it fair to assume there's probably a higher probability of meeting the bar on the primary endpoint in the high expressers relative to the secondary expressers in the overall population?

Arvin, do you want to comment?

Yes. Thank you, Anna. So just to walk through this, the statistical design is designed in such a way that we should have 95% confidence interval, an ability to essentially rule out the lower bound in relationship to the standards of care. In relationship to the design of the study, it will be obviously based upon the data. And the data that we have currently does suggest that there appears to be enrichment by the higher NaPi2b expression. However, again, recognizing we continue to see activity within the lower NaPi2b expressers. And hence, the rationale and strategy behind having this approach to look at both the higher expressers as well as the overall population. But with a built-in ability to have a robust biomarker strategy in order to either use as a complementary or companion diagnostic, so in both settings, you would have still the ability to identify the higher or lower, where it may be enriching for the potential for response.

Got it. That makes sense. And then maybe just a follow-up on the NaPi2b biomarker. Just maybe you can share your current thinking on the cutoff at this point. I think in the past, you've sort of been using 110 on the H-score. Is that changing? Or what's your current thinking there?

So Mike, we always said we will finalize the cutoff when we have the complete data set. The complete data set are the patients, the data set you've seen plus a handful of additional patients where we are waiting for the H-score or we're waiting for our own study, but haven't yet reached their first scan. So we're very close to finalizing that cutoff based on this data set. We almost complete data set, and we'll have the complete data set very shortly.

Our next question comes from the line of Mr. David Nierengarten.

I had one for perhaps Dr. Richardson and Brian. Given the possibility in the relatively near term -- near future, 2 targeted ADCs in ovarian cancer being approved with yours in NaPi2b expressing patients and also, of course, the fully targeted ADC. Maybe for Dr. Richardson, what would be your decision tree for deciding which one to prescribe in late-stage ovarian patients? And then, Brian, on the commercial side and product planning strategy, how are you anticipating planning for that potential scenario?

Thanks for your question. I would say that for the mirvetuximab, the folate receptor, ADC, only about 1/3 of patients with high-grade serous ovarian cancer expressed high folate. So if that drug does get approved, it will only be -- only about 1/3 of patients will be eligible for it. And then in addition, I think you have to look at toxicity profile like we do any time we're choosing the next drug that we're going to treat our patients with. And they definitely have different toxicity profiles. And so those are the kind of conversations typically a treating clinician and their patient have to determine what the next step is as far as drugs. And quite frankly, I'd like to have both as options for my patients because our goal is to try and turn ovarian cancer into a chronic disease. And so my goal is to prolong quality and quantity of life.

Sorry, maybe before Brian answers maybe more to the point, where would you test? Would you test first after platinum patients for folate? Would you consider perhaps prescribing the Mersana agents given more patients are likely to benefit, and that would just kind of -- I don't want to say default, but that would be your first choice or absent a folate test? Or how are you thinking about that test given that there seems to be more discrimination for a folate-receptor-targeted agent on the NaPi2b?

Thanks for that question. I think it's a little premature to be able to answer that, quite frankly, because we'll need to decide do we use the biomarker for NaPi2b or not in which way. Certainly, if NaPi2b has a complementary diagnostic then it's much easier, especially if you have a symptomatic patient to start them on a drug that you don't need to wait testing results for. On average, it can take a week or 2, if you send tissue, in order to get results. And so if a patient's symptomatic, they often don't have time to wait for that in addition to all other delays that occur when you're trying to start somebody on therapy.

Yes, David, thank you for the question on -- and Dr. Richardson, I think you hit all the major points. And I think the key parameters here are one of prevalence of the biomarker to more likely than not that an individual patient would be higher NaPi2b expresser. And the difference in the tolerability profile. I think we're pleased to see over multiple data disclosures, the lack of severe neutropenia, peripheral neuropathy or ocular toxicity in the profile here. And we agree, it's hard to overstate the level of unmet need in this patient population. So more options are good for everyone to help patients live longer, do better with their disease. But I do think the prevalence and the tolerability profile and I think we think our design for the UPLIFT cohort is also quite innovative.

[Operator Instructions] Our next question comes from Mr. Konstantinos Aprilakis.

First, could you provide some color on the size of UPLIFT? Why you're targeting 180 patients versus the 100-patient target enrollment in Immunogen's SORAYA trial, for instance, and if that's an appropriate comp?

Yes. Arvin, I think -- can you comment on that?

Yes. No. Thank you. So just as a reminder, the 180 patients that's based on, again, that 2 shots on goal strategy. And so the 180 patients will include the higher NaPi2b population. And so based upon the projected prevalence of around 65%, 70% of those patients having a higher NaPi2b score, that will give us sufficient numbers in order to robustly evaluate the primary endpoint, which is in the higher NaPi2b population.

Great. And then revisiting the pneumonitis signal, it's not common in ovarian cancer, but did the patient with Grade 5 pneumonitis have metastatic lesions in or near the lung?

No, they did not as far as I'm aware. Arvin, is that correct?

That's right. So this was, unfortunately, obviously, a very complicated patient with 4 lines of prior therapies and advanced disease, but she did not have metastatic lesions within her lungs.

Got it. And then could you comment on potential combinations for XMT-1536 with checkpoint inhibitors, given the pneumonitis signal? Just with the lesions, mirvetuximab in combo with pembro, pneumonitis was deemed a potential overlapping tox. How do you guys think about that and future combinations there?

Go ahead.

So just to address that question actually holistically. I think I'll remind folks of the safety profile as well as the efficacy profile. It really does lend itself towards the potential for combinations, given the lack of that severe neutropenia and the peripheral neuropathy. So whether they be approved agents with chemotherapeutics, including we've already discussed the potential combinations with platinum partners, but as well as other approved agents that are not platinum-based because there is high unmet need in these populations. In addition to that, though, there still continues to be opportunity to potentially combine with other novel agents, including immunotherapeutics, including the PD-1 pathway or other immune-modulatory effects. It's been successfully done with multiple different approved regimens. And there's no current reason to believe that we wouldn't be able to interrogate this clinically.

There are no further questions at this time. I would now like to turn the call over to Ms. Anna Protopapas. You may continue.

Yes. I'd like to thank all of you for participating today. We're excited about the path forward for UpRi as well as the advancement of our next molecules, XMT-1660 and XMT-2056, and we look forward to updating you throughout 2021 of our progress. Operator, I think that concludes the call.

This concludes today's conference call. Thank you for participating. You may now disconnect.