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spk07: Good morning, and welcome to Masana Therapeutics' fourth quarter and year-end 2020 conference call. Currently, all participants are in a listen-only mode. There will be a question-and-answer session at the end of the call. I would now like to turn the call over to Sarah Karmoudi, Executive Director, Investor Relations and Corporate Communications. Please proceed.
spk08: Welcome to Mursana's fourth quarter and year-end 2020 conference call. We issued a press release earlier this morning reviewing our fourth quarter 2020 and full year financial results and business updates, which will be covered on this call. A replay of today's call will be available on the investors and media section of our website. After our prepared remarks, we will open the call for Q&A. Before we begin, I'd like to mention that our call will contain forward-looking statements within the meaning of federal securities law. 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 and the implementation of the company's plans to vary materially, including the risk that preclinical testing or early clinical results may not be predictive of the of the results or success of our ongoing or later preclinical or clinical studies, that the identification, development, and testing of the company's product candidates and new platforms will take longer and or cost more than planned, and that our clinical studies may not be initiated or 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 26, 2021, and subsequent filings. In addition, while we expect that 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 action taken globally to contain and treat the disease. Except as required by law, the company assumes no obligation to update these forward-looking statements publicly, even if new information becomes available in the future. With that, I will turn the call over to Anna Protopopis, Mursana's President and Chief Executive Officer.
spk09: Thank you, Sarah. Good morning, everyone, and welcome to our fourth quarter and full year 2020 Corporate and Financial Update Call. Joining me today with prepared remarks are Arvind Yang, our Chief Medical Officer, Tim Loinger, our Chief Science and Technology Officer, and Brian Descheidner, our Senior VP of Finance and Strategy. I'm also joined by the rest of the executive team who will be available for your questions, including the newest member, Carla Paulson, our Chief Human Resources Officer who joined us in January. Before we start, I want to take the opportunity to introduce Carla. Carla brings with her substantial organizational and talent development experience, which will be crucial as we scale MERSANA to accommodate our robust and maturing pipeline of ADC candidates. Most recently, Carla was Chief Human Resources Officer at Axia Therapeutics, where she played an integral role in building the organization. Before joining AXIA, she served in multiple roles at Vertex for over a decade, including as head of international human resources, where she was instrumental in helping build the Vertex European organization to over 250 employees in just two years. Welcome, Carla. We are thrilled to have you on board. Moving on to the business update. At Mersana, We aspire to become an ADC leader by leveraging our innovative platform to bring important medicines to cancer patients. 2020 was a transformational year for us. We established the potential of our brief to benefit heavily pre-treated ovarian cancer patients and advanced an innovative pipeline of ADCs addressing areas of high-end med need, including XMT-1592, XMT 1660, and XMT 2056, all while strengthening the organization to deliver on the next stage of evolution of MERSADA. In 2021, we're taking the next step in our journey. Our focus is twofold, building upgrades and building out our innovative pipeline. With respect to building upgrades, We will be initiating Uplift, a single arm registration study informed by FDA feedback. In addition, we will set into motion studies designed to bring upward to patients in earlier lines of therapy as we seek to establish it as a foundational medicine in ovarian cancer. Arvind will describe the design of Uplift and the significant potential advantages of our differentiated design. Arvind would also describe upgrade, a first step in a life cycle management plan we will share with you over time. With respect to building out the pipeline, we will work to complete the evaluation of our two NAPI-TP targeted agents in Long Island of Carcinova, UPRI and XMT 1592, and set a clear strategy for next steps, as well as work to advance XMT 1660 and XNT 2056 through IND enabling studies. In parallel, we will continue to leverage our innovative platforms to discover and bring forward additional ADCs that address areas of unmet medical needs. Both Arvind and Tim will describe in more detail our efforts in continuing to build out our pipeline. With the accomplishment of our 2021 goals, we could achieve another transformational year for MERSANA. 12 months from now, we could be substantially enrolled in our pivotal study for UPRI with multiple life cycle management studies underway. And we anticipate having a clear strategy for the potential of NAPI to be lung adenocarcinoma patients and having two new molecules in the clinic. Accomplishment of these goals would put the next stage of transformational MERSANA in sight. the potential for completing our first pivotal study and preparing to launch our first commercial ADC. With that, I would like to turn the call over to Arvid to review Uplift and our Uplift lifecycle management studies we are planning, and then to Tim to review the advancement of our pipeline.
spk04: Thank you, Anna, and thank you, everyone, for joining us today. Let me start by summarizing the data we've generated to date that support the potential for UPRI to become the foundational medicine in ovarian cancer. As you recall, we've disclosed the substantial data from the ongoing study in four different disclosures in the past 12 months, including a comprehensive disclosure on the January 5th of this year. These data support the potential of UPRI to provide significant benefit for heavily pretreated ovarian cancer patients who have exhausted other options, including bevacizumab and PARP inhibitors, and have a poor prognosis. Specifically, we have consistently shown robust activity substantially above the current standard of care, including complete responses, and a tolerability profile without the severe neutropenia, neuropathy, and ocular toxicities that limit other ADC platforms. This has the potential to facilitate the combinability of upbringing with agents used in earlier lines of ovarian cancer treatment. Let me start with Uplift. our single-arm registration strategy in heavily pretreated platinum-resistant ovarian cancer, the first step in our objective to building UPRI as a foundational medicine in the treatment of ovarian cancer. With FDA feedback and with strong support from the cooperative groups both in the U.S. and in Europe, we are well on our way to initiating dosing in Uplift in March. Let me summarize the key features of Uplift. First, the patient population addresses substantial unmet medical needs and affords us the potential for significant label differentiation. Uplift is designed to enroll platinum-resistant patients who have received up to four lines of therapy consistent with the population in the expansion cohort, where we've already seen data supporting the potential for robust activity. The inclusion of patients with four prior lines differentiates uplift from other ongoing and historical studies in late-stage ovarian cancer. Note that Bevacizumab pretreated and Bevacizumab naive patients are included in the uplift cohort in a matter consistent with the Bevacizumab label. This is another important differentiator because it allows us to explore the potential of upgrade to address the unmet medical need of patients who have and have not been previously treated with Bevacizumab in a single study. Second, the design allows for the robust evaluation of the relationship between the biomarker and patient outcomes. We plan to enroll patients regardless of NAPB2B expression, which we believe will also contribute to the speed of enrollment. Nevertheless, the role of the biomarker will be evaluated in Uplift. Specifically, the primary endpoint for the Uplift cohort will be objective response rate in the higher NAPB2B population, while the key secondary endpoint will be the objective response rate in the overall population. This design allows us to more fully evaluate the role of the biomarker to enhance patient outcomes. It's a two-shot-on-goal approach. We expect to enroll approximately 100 patients with higher NAPI 2B expression in the uplift cohort, which can include up to 180 patients in total, depending on the higher NAPI 2B prevalence. Other secondary endpoints will include the duration of response and safety in both the higher NAPI 2B and the overall population. Thirdly, Uplift is designed to ensure that we have a systematic and robust strategy for a commercial diagnostic assay. Specifically, the substantial data set generated in the ongoing expansion cohort will be used to establish the final cutoff for the planned commercial assay that will be used in Uplift. This approach should allow for the evaluation of both the higher NAPI 2B and the overall population. 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. We are on track to finalize the biomarker strategy and the cutoff for the proposed commercial diagnostic in Uplift. Lastly, Uplift will be initiated as an amendment to the current study, allowing us to capture the enrollment momentum we are seeing in the ongoing expansion cohort. In addition to the Uplift strategy, we are focused on the lifecycle management plans that have the potential to build UPRI into a foundational medicine in ovarian cancer. This plan starts with the upgrade phase one umbrella study designed to evaluate UPRI in combination with other ovarian cancer therapies. We first intend to combine with platinum as platinum therapy is currently the mainstay therapy in earlier line platinum sensitive ovarian cancers. Our goal is to initiate upgrade in the third quarter of 2021. However, over the next few months, we will be sharing with you a more complete life cycle management plan as we leverage the potential of UPRI to address patients in earlier lines of therapy. These studies are important next steps in building UPRI as a foundational medicine in ovarian cancer. Moving on to our ongoing efforts to build out the pipeline, we continue to advance as planned on our NAPI to be targeted Dolacentin ADC XMT 1592 in the phase one dose escalation study. We are on track to generate the data set that allows us to make decisions on the path forward in lung adenocarcinoma as we evaluate both UPRI and XMT1592 in this indication with high medical need. In addition, as Tim will describe, we are preparing to advance XMT1660 and XMT2056 into the clinic early next year. We're encouraged with a high level of interest that these two exciting molecules are generating among the KOL community. I will now turn the call to Tim to discuss our exciting early stage ADC candidate.
spk01: Thanks, Arvind, and good morning, everyone. We made significant progress in advancing our pipeline in 2020. The focus for 2021 is to build out the pipeline and further demonstrate our position as leaders in ADC innovation. Today, I will focus on XMT2056, our first immunosynthin sting agonist ADC, and XMT1660, our B7H4 dolaloc ADC. We're very excited about the potential of our immunosynthin ADC platform. As a reminder, in November we held a webinar highlighting the characterization of this platform, and I'd like to briefly summarize the key takeaways from that webinar that explain why we are so excited about this platform and the potential of Sting agonist ADCs. We believe that an ADC approach to activating the innate immune system to fight cancer in a targeted manner is a potential game changer and could be a dramatic next step in immune oncology. The Sting pathway has been studied extensively and validated to play a central role in immune activation. but we believe that delivery challenges to date have limited sting agonists from reaching their full potential. Immunosensin leverages our unique expertise in ADC design and optimization to overcome those limitations. Our approach is also differentiated from ADCs carrying toll-like receptor agonist payloads. With immunosensin, we deliver what we call a one-two punch. Unlike toll-like receptors or TLRs, STING is expressed in both tumor cells and immune cells. And we have demonstrated preclinically that we can productively activate the STING pathway in both these cell types in a concerted and targeted fashion, delivering the one-two punch with potential to increase the therapeutic index. That's not possible with TLRs because they are not expressed in tumor cells, but only in the immune cells. Preclinically, we have validated the broad potential of our immunosynthin ADC pipeline, not only for a single target, but across a suite of multiple targets and multiple animal models, demonstrating robust activity after a single low dose. We've also demonstrated excellent tolerability in multi-dose non-human primate studies with IV dosing, at exposure levels far exceeding those that result in complete responses in mouse models, indicating the potential for a wide therapeutic index. XMP2056 is our first immunosynthin ADC that is progressing through IND-enabling studies with the objective of moving into clinical development in early 2022. I'd now like to turn to our novel dolusynthin platform. In early January, we introduced you to our next doula-symptom ADC, XMT1660, which is the first in class ADC targeting B7H4. We believe that B7H4 is a well-suited target for a doula-lock ADC for the following reasons. First, B7H4 is expressed on multiple tumors with high unmet medical need, and provides us the opportunity to target these tumors with our cytotoxic antitubulin mechanism. Second, we also know, based on preclinical studies, that our DOLALOC ADCs lead to immunogenic cell death and that our DOLALOC payload can activate dendritic cells in the tumor, both of which can prime a potential immune response as well. Because B7H4 is expressed on tumor cells, but also on immunosuppressive tumor-associated macrophages, it provides the potential opportunity to co-opt those cells in a targeted manner to further contribute to both the cytotoxic and immunogenic effects and create what we describe as a perfect storm in the tumor microenvironment. Another feature of B7H4 is that it is in the same family as PD-L1, but literature suggests B7H4 and PD-L1 expression are mutually exclusive, providing for the potential to address unmet medical needs in patients who either do not respond or progress with checkpoint therapy due to lack of PD-L1 expression, as they are likely to express B7H4. Leveraging our unique ability for DAR ranging, we selected XMP1660 as our development candidate from a range of variant options evaluated based on efficacy and tolerability. We are hard at work and on track to complete IND-enabling studies on a timeframe that we expect will allow us to initiate clinical studies in early 2022. We are very excited about the potential for both of these innovative earlier stage development candidates and are pleased to announce the two abstracts for XMP2056, and one abstract for XMT1660 have been accepted as e-posters at the AACR virtual meeting to be held in April. We look forward to sharing further preclinical data from these programs at that time. And with that, I'll now turn the call over to Brian for an overview of our financial results.
spk11: Thank you, Tim. Good morning, everyone, and thank you for joining us. I'll now review some of the key financial highlights from our fourth quarter 2020 results. And I'll start with our cash position. We ended 2020 with $255 million in cash and cash equivalents. Net cash used in operating activities in the fourth quarter was $17.3 million. We expect that our available funds will allow us to meet our current operating plan commitments for approximately the next two years. In addition to our current cash position, we have the option to draw funds through the amended existing debt financing agreement. with Silicon Valley Bank refinanced in August of last year. And now, some of the key highlights from our fourth quarter 2020 financial results. Research and development expenses for the fourth quarter of 2020 were approximately $22.9 million, compared to $12.4 million for the same period in 2019. The difference was primarily due to an increase in UPRI and XMT 1592 clinical expenses. an increase in manufacturing activities for UPRI and our Discovery Stage programs, increased headcount, and a non-cash increase in the valuation of stock-based awards as a result of stock appreciation. All of these were partially offset by a decrease in preclinical development and manufacturing expenses for XMT 1592. General and administrative expenses for the fourth quarter of 2020 were approximately $5.9 million compared to $4.2 million in the same period in 2019. The increase was primarily due to an increase in consulting and professional fees, an increase in facility-related costs as a result of the extension of our lease in March 2020, and a non-cash increase in the valuation of stock-based awards as a result of stock appreciation. Net loss for the fourth quarter of 2020 was $28.8 million, or 42 cents per share, compared to a net loss of $16.2 million, or 34 cents per share, in the same period of 2019. Weighted average common shares outstanding for the quarters ended December 31, 2020 and December 31, 2019 were approximately 69 million and 48 million respectively. I'll now turn the call back to Anna.
spk09: Thank you, Brian. Before we open the call to questions, I will like to outline our goals and milestones for 2021. which center on building UPRI as a foundational medicine in the treatment of ovarian cancer and building out our pipeline to demonstrate our position as leaders in ADC innovation. I'll start with UPRI. First, we are on track to initiate the planned uplift single arm registration strategy in platinum resistant ovarian cancer this quarter. 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 the combination study with platinum in key three of this year. We are considering additional life cycle management studies, and we will share these details as we finalize our plan. We are excited for the potential of these studies and the opportunity to build UPRI as a foundational medicine for ovarian cancer across lines of therapy with the objective of creating a differentiated label in this indication. Lastly, for UPRI, we expect to have a meaningful number of lung cancer patients enrolled in the expansion study and to be able to provide a data update from this cohort in the second half of 2021. For XMT1592, our NABI 2B-Dollar symptom ADC 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 upper lung adenocarcinoma expansion data with the XMP1592 data to make decisions as to which molecule we will take forward based on PK, tolerability, as well as activity. We expect to be able to outline our further development plan for XMT-1592 in the fourth quarter of 2021. For XMT-1660, we plan to complete IND-enabling studies in 2021 and initiate a phase one dose escalation study in early 2022. For XMT-2056, our first-in-acronyst ADC from the Unisymptom platform, we plan to complete IND-enabling studies and disclose the target by the end of this year and initiate a phase one dose escalation study in early 2022. Finally, we will continue to leverage our proprietary platform and continue to expand our pipeline of innovative ADC candidates while proactively evaluating potential collaborations for current and future programs. In closing, we have another busy year ahead of us with multiple value-driving opportunities as we focus on building up and building out the pipeline. With a promisingly dastard and exciting pipeline, differentiated platforms, a highly experienced team, and a strong balance sheet, we believe we are well-positioned to execute against these goals and to ultimately reach our overarching mission to discover and develop life-changing ADCs for patients fighting cancer. With that, I will turn the call over to the operator for Q&A.
spk07: Thank you. Ladies and gentlemen, if you wish to ask a question at this time, please press star, then 1 on your touch-tone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you please place your line on mute once your question has been stated. Our first question comes from the line of Jonathan Chang with SBB Lyric. Your line is open. Please go ahead.
spk12: Hi team, this is John Barrett on for Jonathan. Congrats on the progress in 2020. My first question is now that you're closer to the initiation of uplift, what are your expected timelines for the trial related to full enrollment and then obviously potential readout of top line data?
spk09: Yeah, great question, Jonathan. I think we're very focused on getting uplift up and running. We're really on the cusp of beginning to dose patients. We have, as you know, agreed with the FDA that we could do this as an amendment to the existing trial. And if you recall, we indicated on January 5th that we had about 40 sites already as part of the expansion cohort. We're working with the cooperative groups in Europe and we'll be bringing additional sites up in Europe. And we feel quite good about the momentum behind the agent and the momentum we hope will translate into enrollment and uplift. At this point, we're holding back from giving specific guidance. We just want to get the trial up and running. But I think a lot of both the support from the cooperative groups, the momentum we've seen in enrollment in the expansion cohorts makes us, you know, optimistic that a year from now we'll be substantially enrolled in the study. But I think we'd like to wait a little bit before we give definitive guidance.
spk12: That's helpful. And following up, Given this is more for clarity, given the two endpoints of ORR in the higher net B2B population and the ORR in the overall population, is it possible that you have two top line data readouts where you have an ORR top line for first the higher population and then later on the ORR for the entire population? Or do you expect those to be coming at the same time?
spk09: I'll let Arvind answer the question, but I think my expectation is that it would be coming out at the same time, but Arvind, maybe you can confirm that.
spk05: Yeah. No, thank you, Anna. And just to confirm, that's correct, meaning that based upon the way the study is designed, we would have both endpoints at the same time.
spk12: Got it. And just one last one. What do you see as the bar for a go, non-go decision in lung cancer, and what gives you confidence that UPRI could succeed in lung cancer.
spk09: So let me answer your second question, and maybe I'll then ask Brian to answer your first question. So what do we know about NABI-2B in lung cancer? We know that it's expressed there in lung adenocarcinoma, not in other histologists. And we've published data where we showed the work we've done to understand the expression. We saw in, if you recall back at the data we disclosed in March, at the NTD, we had several lung patients, we had one partial response, and we had multiple patients with prolonged stable disease. So the target is there. We've seen early signs of activity. We are enrolling an expansion cohort of about 40 to 45 patients. We did say that what we're seeing both in tissue banks as well as with patients, is that the distribution, the prevalence of NAPI TB high is different in ovarian than is in lung and is in ovarian. In ovarian, if we were to take the definition of NAPI TB high as being that age score of about 110, you know that in ovarian, about two-thirds of patients are above that. I think what we're seeing in the clinic is that more like 40% of patients are above that threshold and are on the NAPI TB high side. So I think we need to complete the expansion cohort and really understand the profile of the agent, but the target is there and we've seen some early signs of activity. Brian, do you want to talk about the BAR?
spk11: Sure. So in non-small cell lung cancer, the standard of care following progression on checkpoint inhibitors and platinum-based chemotherapy or failure of targeted therapy for patients with tumors that harbor the oncogenic driver mutations that make those appropriate is docetaxel alone or in combination with targeted therapy. You know, this standard of care is an overall response rate of somewhere between 14 and 23% in a median PFS of three to four months. So remarkably similar, actually. to the performance of the single-aid and chemotherapy standard care in platinum-resistant ovarian cancer. So the unmet need in this space remains very significant. And, you know, to your question about the bar, it really comes down to the totality of data, right? There's the activity. There's the tolerability profile where we think we've shown some real differentiation over other platforms that also come into play.
spk12: Thank you.
spk07: Thank you. And our next question comes from the line of Konstantinos Abalaskas with Stifel. Your line is open. Please go ahead.
spk03: Good morning. Thanks for taking my questions. As we wait for Uplift to initiate, can you disclose how many additional patients have been enrolled into the ongoing expansion cohorts since your last readout? And what are the current plans, if any, for additional data disclosures from the upward expansion cohorts? Do you plan on presenting presenting any preclinical data that would be further validating to potential combinations in upgrade?
spk09: Yeah. Thanks, Constantino, for that question. So we are continuing to see momentum in enrollment of the expansion cohort. So I think we've always said that that's encouraging in terms of converting the expansion cohort into the uplift. In terms of data disclosures, We have a few different opportunities, and let me just outline our considerations here. We've done four data disclosures between March of 2020 and January 5th. I think we've disclosed a very, we've shown a very consistent and promising profile for UPRI. We're now single-mindedly focused on getting UPLIFT up and running. enrolling as quickly as possible, and bringing this promising agent to patients. As we convert the expansion cohort to Uplift, that's happening on a site-by-site basis. So at some point, we're going to close down the expansion cohort. We're going to lock and clean the database. And I think that could give an opportunity for us to disclose the data, either as a publication at the scientific conference or both. I think at this exact point, we're not in a position to know what the exact timing is of that disclosure, but obviously we have that option in front of us. We are also finalizing the expansion cohort, the cutoff, sorry, the cutoff for the for the biomarker, and I think that's another opportunity for us to share more data with you. And I think we're trying to determine what is the right forum to disclose that, but that would be another opportunity for data disclosure. But again, this is a year where we're very focused on initiating uplift, initiating upgrade, and really putting in motion the studies that will bring this agent to patients And we will, of course, disclose data along the way, but our top priority is to get these studies up and running.
spk03: Thanks for that. That was very helpful. And then I guess just coming at it from just a different angle for upgrade, you know, how should we think about the other potential combination partners that you're thinking about in the umbrella study? And, again, is it going to be sort of preclinical data to support those decisions that we would see or, you know, I guess just underlying rationale for the combinations that you that you presume?
spk09: So we're working through all those additional combinations, and I think we'll be able to share more data in the near term. But there are multiple options here, and I know that Arvind and Tim are collaborating to do what is necessary from a preclinical standpoint to understand the potential of some of the additional combinations.
spk03: All right, perfect. Thanks, guys. Congrats on the progress.
spk07: Thanks. Thank you. And our next question comes from the line of force. Peeker with Cowan. Your line is open. Please go ahead.
spk13: Good morning. My first question is on the diagnostic side. You mentioned that there's a possibility here of a companion versus a complementary diagnostic. Is there a difference from the FDA regulatory perspective for either of those diagnostic approaches?
spk09: Arvind, do you want to take this?
spk04: Sure, let me start. And, of course, just to address the question between a companion versus a complementary diagnostic, for a companion diagnostic, the guidance really is in relationship to that test is utilized to identify and select patients that would then have an indication in order to be treated with the drug. So in the instance that the companion diagnostic would be utilized, it would be primarily based on the fact that the benefit risk is focused specifically on those patients with a higher NAPB2B status. Now, in a secondary instance where a complementary diagnostic would have value is whereby the benefit risk is considered supportive to approve in the broad indication, meaning regardless of NAPB2B status. However, having a diagnostic available may be helpful for physicians to understand if there's differential benefit risk within the populations of the higher or lower NAPI 2B status. And so the clear distinction here is that in the complementary diagnostic, there would not be a requirement for a test result in order for a physician to be able to potentially utilize OPRI in patients, assuming it was approved in that broader indication.
spk13: Gotcha. And my second question is, For the upgrade study, is the goal to ultimately find a combination for running a future pivotal study for that combination, or do you just plan to generate enough data for a compendia listing in parallel with the uplift regulatory study so that you could complement the approval based on uplift?
spk09: Boris, thank you for the question. We're actually finalizing the designs of our confirmatory trial, and we will have an opportunity to share it externally in the near term. So I would ask you to be a little patient with us as we finalize those plans. But our objective, as we've said before, is to have a confirmatory trial in the earlier lines of therapy and be able to move our brief as a treatment in platinum sensitive.
spk13: Great. Thank you very much for taking my question.
spk07: Thank you. And our next question comes from the line of Jessica Fee with JP Morgan. Your line is open. Please go ahead.
spk06: Hey, guys. Good morning. Thanks for taking my question. First is when do you expect to solidify the cutoff for higher NAPI 2B expression? And second is, to the extent that the cutoff for higher NAPI 2B expression changes relative to what you have been using, can we expect you to update the expansion data analyzed using that new cutoff so investors can get a clearer sense of the potential efficacy in this group?
spk09: Yeah, Jess, that's a great question. We are in the process of finalizing that cutoff and we will be sharing that data. We are trying to you know, complete and wrap up our work and then find the right forum to do that, as well as really describe the whole strategy around the diagnostic, the commercial diagnostic. So in that context, we will also show the whole analysis, which includes really showing the expansion cohort data that led us to the determination of the cutoff.
spk07: Great. Thank you. Thank you. And our next question comes from the line of Tom Schrader with BTIG. Your line is open. Please go ahead.
spk10: Thank you. Let me congratulate everyone on a nice year. I had a question kind of triggered by your careful language about prior Avastin use in Uplift. Who's not going to have Avastin? That patient's with platinum-resistant cancer and then three lines of chemo? And are they going to be sicker?
spk09: Brian, would you like to take this question or Arvind?
spk11: Sure, I can start and then Arvind, you can join in. So, Tom, thanks for the question. And I think this is a really important differentiator here in how we're pursuing uplift and what we think is important for a label. So you will notice from the demographics of our expansion data that about 70% of patients that we enrolled had prior Avastin. And now there may be – there's reasons it's that high. Avastin is approved in the frontline, it's approved in platinum-sensitive relapse, and it's approved in platinum-resistant disease. But not everybody is really a candidate for Avastin. But that's a minority of patients. And that might be because of a comorbidity or concerns about bowel obstruction or wound healing or hypertension. What we wanted, the important thing here, though, is in a single study, in a very capital efficient way, we want to be able to address both populations, the people who have had Avastin previously and the people who have not had Avastin previously. And because of the nature of the Avastin label, we're able to do that in one study. Avastin in platinum-resistant disease is only approved for patients who have had only one or two prior lines of therapy. So for patients with three or four, we can pursue a fast path to market while also including patients who may not have seen Avastin before. And this is a really important point. It allows us to go after a very broad patient population in a single, single-arm study.
spk10: All right, great. Got it. And then a question on upgrade. If you are combining with platinum to get this through IRBs and stuff, will you have to give patients full-dose platinum and then titrate in your drug, or can you start at lower levels of both drugs, do you think?
spk09: Arvind, you want to take that?
spk04: Yeah, sure. So we'll be coming out with, obviously, our trial design in relationship to the upgrade. But what I would want to start with from the standpoint is, remember, one of the key differentiators for UPRI is really from the standpoint of, again, the fact that our safety profile has been quite consistent with the lack of that severe neutropenia, the peripheral neuropathy, as well as the ocular toxicities. So it sets us up in a way to really fully appreciate and maximize the potential to combine, in particular with platinum agents where there can be associated neutropenias as one example. And so we'll be coming out with a trial design. Obviously, safety is paramount in relationship to these Phase I studies, and so certainly dose escalation is quite standard just in relationship to how these studies are designed in order to ensure that we're appropriately dose escalating and maximizing the ability for these two compounds to be either additive or potentially synergistic.
spk12: Okay, great. Thank you.
spk07: Thank you. And our next question comes from the line of David Nierengarten with Bloodbush Securities. Your line is open. Please go ahead.
spk02: Thanks for taking the question. Maybe a follow-up to a couple other ones on upgrade study. Do you anticipate or is there a possibility to – use UPRI as a maintenance therapy or, you know, extend the dosing beyond the fixed platinum cycles, or are you planning to, you know, focus in on dosing with platinum for that fixed set of cycles?
spk04: Thanks.
spk09: David? Yeah, go ahead.
spk04: Oh, sure. I was just going to say, I think it leads back to the response we mentioned with Tom, just from the standpoint that Again, that tolerability profile lends itself toward the ability to dose really to potentially progression in regards to operability. So as we're evaluating the dose escalation strategy here, we're really going to maximize the characteristics of each of these compounds to make sure that we're trying to maximize the benefit for patients per se. So certainly from a combinability perspective, we do believe that there is going to be the potential to combine, and that's how we're thinking about approaching this. And, again, I think with the line of sight toward the idea that we will try to maximize each of these agents in a way to benefit most of those patients.
spk02: Okay. And, I mean, would there be, or I know you're disclosing details later, but would there be an option, do you think, for patients to continue on maintenance therapy or anything like that as part of the a study assuming you begin with a fixed set of cycles to combine with platinum?
spk04: Yeah. So the short answer is that is definitely under consideration from the standpoint that remembering that for chemotherapies, it's typically a fixed number of cycles, and we have not seen that type of treatment approach with upper monotherapy. Okay. Okay.
spk07: Thank you. And I'm showing no further questions at this time. And I would like to turn the conference back over to Anna Protopopoulos for any further remarks.
spk09: I just want to thank you all for listening in. This is another really exciting year for us as we really build UPRI and build out the pipeline. So thank you very much for your continued support.
spk07: Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program, and you may all disconnect. Everyone, have a great day.
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