Q4 2024 Mersana Therapeutics Inc Earnings Call
Operator: Thank you, Operator, and good morning, everyone.
Thank you operator, and good morning, everyone. Before we begin. Please note that this call will contain forward looking statements within the meaning of federal Securities laws. These statements may include but are not limited to those related to the potential clinical benefits of our product candidates and platforms, our clinical trial progress and designs.
Unknown Executive: Before we begin, please note that this call will contain forward-looking statements within the meaning of federal securities laws. These statements may include, but are not limited to, those related to the potential clinical benefits of our product candidates and platforms, our clinical trial progress and designs, dosing and patient management strategies, addressable market opportunities, anticipated milestones and data disclosures, and cash runway. Each of these forward-looking statements is subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements.
Dosing and patient management strategies addressable market opportunities anticipated milestones and data disclosures and cash runway.
Each of these forward looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected in such statements. These risks and uncertainties are discussed in our quarterly report on Form 10-Q filed with the Securities and Exchange Commission on November 13th 2024, and in subsequent SEC filings.
Unknown Executive: These risks and uncertainties are discussed in our quarterly report on Form 10-Q, filed with the Securities and Exchange Commission on November 13, 2024, and in subsequent SEC filings. Our filings are available at sec.gov and on our website, mersana.com. Except as required by law, we assume no obligation to update forward-looking statements publicly, even if new information becomes available in the future.
Filings are available at SEC Gov, and on our website Marsano dotcom.
Sept as required by law, we assume no obligation to update forward looking statements publicly even if new information becomes available in the future.
Jason Fredette: On today's call, we have Mersana's Chief Executive Officer, Dr. Marty Huber and our Chief Operating Officer and Chief Financial Officer, Brian DeSchuytner. With that, let me turn the call over to Marty to begin the discussion. Thank you, Jason, and good morning, everyone. Over the past several months, we have accomplished a great deal here at Mersana. Most notably, with our lead dolacenthin ADC, Emily, we reported positive initial clinical data, started the expansion portion of our phase one trial, and were granted an additional fast-track designation for a growing portion of the breast cancer population that has previously been treated with a topoisomerase I inhibitor, or TOPA1-ADC.
Speaker Change: On today's call, we have <unk>, Chief Executive Officer, Dr. Marty Huber, and our Chief operating Officer, and Chief Financial Officer, Brian to shape now with that let me turn the call over to Marty to begin the discussion.
Marty Huber: Thank you, Jason and good morning, everyone.
Speaker Change: Over the past several months, we have accomplished a great deal you're at Masada.
Speaker Change: Most notably with our lead Dulles sent that ADC, Italy, we reported positive initial clinical data started the expansion portion of our phase one trial and were granted an additional fast track designation for a growing portion of the breast cancer population that has previously been treated with a total isomerase one inhibitor.
Speaker Change: We're topel won a D C. At the same time, we advanced phase one dose escalation with X M. T 2056, our lead immuno sent that ADC, while also supporting our collaborators, let's focus first on Emily Masonic ADC targeting <unk> seven inch four inch.
Martin Huber: At the same time, we advanced phase one dose escalation with XMT-2056, our lead immunosynthin ADC, while also supporting our collaborators. Let's focus first on Emily, Mersana's ADC-targeting B7H4. In January, we reported initial clinical data from 130 patients who were enrolled in dose escalation and backfill cohorts as of December 13th, 2024 data cutoff. From a safety and tolerability standpoint, Emily was observed to be highly differentiated within the ADC space. The most common treatment-related adverse events of any grade were transient increases in AST, generally asymptomatic and reversible proteinuria, generally low-grade nausea, and low-grade fatigue. Importantly, unlike many other ADCs, we did not see dose-limiting neutropenia, neuropathy, ocular toxicity, interstitial lung disease, or thrombocytopenia.
Speaker Change: In January we reported initial clinical data from 130 patients who enrolled in dose escalation and backfill cohorts as of December 13th 2024 data cut off from a safety and Tolerability standpoint, Emily was observed to be highly differentiated within the ADC space.
Speaker Change: It's common treatment related adverse events of any grade were transient increases in E. S. T generally asymptomatic and reversible proteinuria generally low grade nausea, and low grade for T. Importantly, unlike many other adcs, we did not see dose limiting neutropenia neuropathy and ocular toxicity.
Speaker Change: Mr Chau lung disease or thrombocytopenia.
Martin Huber: This provides us with the confidence that Emily could have an attractive monotherapy profile. Just as importantly, we believe it also could enable combinations with standards of care like platinum chemotherapy and other ADCs that our competitors would be challenged to pursue. From a clinical activity standpoint, confirmed objective responses were observed in all enrolled tumor types. These included patients with triple negative and hormone receptor positive breast cancer, endometrial cancer, ovarian cancer, and adenoid cystic carcinoma type 1, otherwise known as ACC1. At intermediate doses, which ranged from about 38 to 67 milligrams per meter squared or about one to two milligrams per kilogram, the confirmed objective response rate was 23% across all tumor types with high B7H4 expression, which we defined as an IHC score of 70% or more.
Speaker Change: This provides us with the confidence that Emily could have an attractive monotherapy profile.
Speaker Change: Just as importantly, we believe it also could enable combinations with standards of care like platinum chemotherapy and other adcs that our competitors would be challenged to pursue.
Speaker Change: Okay.
Speaker Change: From a clinical activity standpoint confirmed objective responses were observed in all enrolled tumor types. These included patients with triple negative and hormone receptor positive breast cancer endometrial cancer ovarian cancer, and adenoid cystic carcinoma type one otherwise known as a C. C. One at intermediate doses, which range from about <unk>.
Speaker Change: 48 to 67 milligrams per meter squared or about one to two milligrams per kilogram. The confirmed objective response rate was 23% across all tumor types with high E. Seven H for expression, which we defined as an IHG score of 70% or more.
Martin Huber: Focusing specifically on the invaluable patients in this dose range with B7H4 high triple negative breast cancer, the confirmed ORR was also 23%. At the end of 2024, we initiated the expansion portion of our trial in patients with TMBC who have previously been treated with at least one topo-1ABC, a population with a very high unmet need. We believe we are positioned for success for a few key reasons. The first is the dose we're utilizing, the second is our inclusion criteria, third is the standard of care for these patients today, and the final factor is the competitive environment in which we are operating.
Speaker Change: Focusing specifically on the Evaluable patients in this dose range with these seven H for high Triple negative breast cancer.
Speaker Change: Confirmed or are was also 23% at the end of 'twenty 'twenty four we initiated the expansion portion of our trial in patients with T. M. D. C who have previously been treated with at least one telco at one agency.
Speaker Change: Population with a very high unmet need we.
Speaker Change: We believe we are positioned for success for a few key reasons. The first is the dose for utilizing the second is our inclusion criteria.
Speaker Change: Third is the standard of care for these patients today and.
The final factor is the competitive environment in which we are operating well.
Martin Huber: Let's begin with the dose. Generally speaking, as you might expect, we have seen that clinical activity tends to increase along with Emily's dose. As I mentioned, the 23% ORR we observed was generated across a range of doses from about 38 to 67 milligrams per meter squared. We have brought the top dose from this range, specifically 67.4 mg per m2 every 4 weeks, into expansion. As we previously reported, this particular dose was well-tolerated. Additionally, each of the four B7H4 high patients who received this dose achieved target legion reductions, and each also remained on treatment for durations of approximately 16 weeks or more as of the date of cut-off.
Speaker Change: Let's begin with the dose generally speaking as you might expect we have seen the clinical activity tends to increase along with Emily's dose.
Speaker Change: As I mentioned, the 23% or are we observed was generated across a range of doses from about 38 to 67 milligrams per meter square.
Speaker Change: We have brought the top dose from this range, specifically 67.4 milligrams per meter squared every four weeks into expansion as.
Speaker Change: As we previously reported this particular dose was well tolerated.
Speaker Change: Additionally, each of the four B seven H for high patients who received this dose achieved target lesion reductions in each also remained on treatment for durations of approximately 16 weeks or more as of the data cutoff.
Martin Huber: A second factor that can influence response is prior treatment. This is well established in oncology, and specifically in triple negative breast cancer. As a reminder, the 23% ORR that we observed with Emily in TNBC was generated in a population of 13 evaluable patients. 12 of these patients received more than three lines of prior therapy, and all had received at least one TOPA1 ADC. These data compare favorably to historical benchmarks. For instance, a 23% ORR was also seen with Tredelby and TMBC patients who received more than three prior lines of therapy in the Phase III Ascent Study.
Speaker Change: A second factor that can influence response as prior treatment. This is well established in oncology.
Speaker Change: Typically in triple negative breast cancer.
Speaker Change: As a reminder, the 23% or are that we observed with Emily and T. N. D. C was generated a population of 13 Evaluable patients 12 of these patients received more than three lines of prior therapy.
All have received at least one top of one ADC.
Speaker Change: These data compare favorably to historical benchmarks for instance, a 23% or are was also seen which would all be in T. M. D. C patients who received more than three prior lines of therapy in the phase III ascent study.
Martin Huber: But of course, this was in a topo-naive setting. Trudelvy's ORR increased to nearly 40% in patients who received only 2 or 3 prior lines of therapy. In expansion, we are limiting enrollment to patients with a maximum of four prior lines, while also mandating that at least one prior treatment must have been a TOPA 180C. It is also important to keep in mind what the standard of care is in TMDC today. In a sense, the control arm, which was single-agent chemo, had an ORR of only about 5%. And finally, there is the competitive environment. We view recent developments within the B7H4-ADC landscape as favorable for Emily.
Speaker Change: But of course this wasn't a telcos I E.
Speaker Change: To adobe's or are increased to nearly 40% in patients received only two or three prior lines of therapy.
Speaker Change: And expansion, we are limiting enrollment to patients with a maximum of four prior lines. While also mandating that at least one prior treatment must have been a top of one AUC.
Speaker Change: It is also important to keep in mind, what the standard of care isn't tnt's each day.
Speaker Change: In a sense the control arm, which was single agent chemo had an O R. R of only about 5%.
And finally, there is the competitive environment.
Speaker Change: We view recent developments within the B seven H for ADC landscape is favorable for Emily.
Martin Huber: Most notably, the company that we have viewed as our primary would-be competitor within the breast cancer space, Pfizer, recently announced that it had discontinued development of its B7H4-ADC candidate. The other B7H4 ADCs that are at a similar stage of clinical development as us all have TOPA1 payloads. As a result, unlike Emily, we believe they are subject to TOPA1 resistance mechanisms. In fact, some of these companies appear to be excluding patients who have received prior TOPA1 therapies from their clinical trials. This positions EMILY as the most advanced or statin ADC in the class, which provides us with a significant opportunity in breast cancer.
Speaker Change: Most notably the company that we are viewed as our primary would be competitive within the breast cancer space, Pfizer recently announced that it had discontinued development of its b seven age for ADC candidate.
Speaker Change: The other b seven each for Adcs that are at a similar stage of clinical development as US all have total one payloads.
Speaker Change: As a result, unlike Emily we believe they are subject to total one resistance mechanisms. In fact, some of these companies appear to be excluding patients who have received prior tougher one therapies from their clinical trials.
Speaker Change: This positions Emily as the most advanced or statin ADC in the class, which provides us with a significant opportunity in breast cancer.
Martin Huber: We are pleased with the level of investigator interest and engagement we are seeing. And while TMBC is our immediate focus, given the clinical activity we have seen across all tumor types, we are excited by Emily's potential in other indications as well. And so, enrollment continues at our initial expansion dose of 67.4 milligrams per meter squared. We also continue to investigate doses up to 95 milligrams per meter squared in escalation of backfill cohorts delays. We're pleased to report that we officially amended our clinical trial protocol in late January as we seek to mitigate the proteinuria-related dose that we were seeing at high doses.
Speaker Change: We are pleased with the level of investigator interest and engagement, we are seeing and while T. M. B C has our immediate focus given the clinical activity. We have seen across all tumor types. We are excited by Italy's potential in other indications as well.
Speaker Change: And so enrollment continues at our initial expansion dose of $67 four milligrams per meter squared.
Speaker Change: We also continue to investigate doses up to 95 milligrams per meter squared and escalation of backfill cohorts delays. We're pleased to report that we officially amended our clinical trial protocol in late January as we seek to mitigate the proteinuria related dose that we were seeing at high doses.
Martin Huber: We expect these efforts will help us identify a second dose for our second expansion cohort in post-TOPO-1 TNBC later this year.
Speaker Change: We expect these efforts will help us identify a second dose for a second expansion cohort in post total one T. N. B C. Later this year and we plan to present additional data from dose escalation of backfill later this year as well.
Martin Huber: And we plan to present additional data from dose escalation and backfill later this year as well.
Martin Huber: Moving on to other areas, we also have advanced the dose escalation portion of our Phase 1 clinical trial of XMT-2056 in recent months. 2056 is our immunosymptom sting agonist ADC targeting a novel epitope of HER2. Later in 2025, we plan to present initial pharmacodynamic data from this clinical trial that helps to characterize this candidate's ability to selectively activate the sting pathway in HER2-expressing tumors. And finally, I would like to note that we continue to make solid progress in our dolosynthin research collaboration with J&J and our immunosynthin research collaboration with Merck KGA.
Speaker Change: Moving on to other areas. We also have advanced the dose escalation portion of our phase one clinical trial of <unk> 2056. In recent months 2056 is our immuno symptom Sting agonist ADC targeting a novel epitope of her to.
Speaker Change: Later in 2025, we plan to present initial pharmacodynamic data from this clinical trial. It helps to characterize this candidates ability to selectively activate the sting pathway in her two expressing tumors.
Speaker Change: Yes.
Speaker Change: And finally I would like to note that we continue to make solid progress in our Dulles Simpson research collaboration with J&J and our imminent said the research collaboration with Merck Kgs.
Brian DeSchuytner: With that, let's turn things over to Brian for some color on our financials. Thank you, Marty. Beginning with our balance sheet, we ended 2024 with $134.6 million in cash, cash equivalents, and marketable securities. We continue to expect that our capital resources will support our current operating plan commitment into 2026.
Speaker Change: With that let's turn things over to Brian for some color on our financials.
Brian: Thank you Marty beginning with our balance sheet, we ended 2024 with $134 $6 million in cash cash equivalents in marketable securities. We continue to expect that our capital resources will support our current operating plan commitments into 2026. Please note that our cash runway guidance does not assume any future milestone payments.
Brian DeSchuytner: Please note that our cash runway guidance does not assume any future milestone payments that we may earn from our current collaborations or proceeds that we may realize from future collaborations. Net cash used in operating activities for the fourth quarter of 2024 was $19.3 million, which is down significantly from $32 million in net cash used in operating activities during the year-ago quarter. This decrease primarily reflects our portfolio reprioritization efforts, including the OPEX reductions we implemented in the second half of 2023 as part of our restructuring. Turning to our income statement, collaboration revenue for the fourth quarter of 2024 was $16.4 million, compared to $10.7 million for the same period in 2023.
Brian: But we may earn from our current collaborations or proceeds that we may realize from future collaborations.
Brian: Net cash used in operating activities for the fourth quarter of 2024 was $19 $3 million, which is down significantly from $32 million and net cash used in operating activities. During the year ago quarter. This decrease primarily reflects our portfolio re prioritization efforts, including the Opex reductions we implemented in the second half of 2023 as part of our.
Brian: Restructuring.
Brian: Turning to our income statement collaboration revenue for the fourth quarter of 2024 was $16 4 million compared to $10.7 million for the same period in 2023 the year over year change was primarily related to increased collaboration revenue recognized under our agreements with J&J, Mark Hey, J E N G S K.
Brian DeSchuytner: The year-over-year change was primarily related to increased collaboration revenue recognized under our agreements with J&J, Merck AJA, and GSK. Research and development expenses for the fourth quarter of 2024 were $22.3 million, compared to $21.5 million for the same period in 2023. For the most recent quarter, approximately $1.7 million of this spending was related to non-cash, stock-based compensation. The year-over-year change was primarily related to increased costs associated with manufacturing and clinical development activities for AMELIE and XMT-2056, which were partially offset by reduced costs related to clinical development activities for our discontinued candidate, OPRA. General and administrative expenses for the fourth quarter of 2024 declined to $8.9 million compared to $10.1 million during the same period in 2023.
Brian: Research and development expenses for the fourth quarter of 2024 were $22 $3 million compared to $21.5 million for the same period in 2023.
Brian: For the most recent quarter approximately $1 $7 million of this spending was related to noncash stock based compensation the year over year change was primarily related to increased costs associated with manufacturing and clinical development activities for Emily and X M. T 2056, which were partially offset by reduced costs related to clinical development activities for our discontinued can.
Brian: Operator.
Brian: General and administrative expenses for the fourth quarter of 2024 declined to $8 9 million compared to $10 1 million. During the same period in 2023, approximately $1.7 million in noncash stock based compensation expenses were included in G&A for the most recent quarter the year over year decline was primarily related to reduced.
Brian DeSchuytner: Approximately $1.7 million in non-cash, stock-based compensation expenses were included in G&A for the most recent quarter. The year-over-year decline was primarily related to reduced employee compensation expenses following our restructuring in 2023 and reduced consulting and professional services. And finally, Mersana's net loss for the fourth quarter of 2024 was $14.1 million, compared to a net loss of $19.5 million for the same period in 2020.
Brian: Employee compensation expenses, following our restructuring in 2023 and reduced consulting and professional services fees.
Brian: And finally, where Sun is net loss for the fourth quarter of 2024 was $14 1 million compared to a net loss of $19 5 million for the same period in 2023.
Unknown Executive: That concludes our business update.
Brian: That concludes our business update operator would you. Please open the call to questions from the audience.
Operator: Operator, would you please open the call to questions from the audience? We will now begin the question and answer session. To ask a question, you may press star, then 1 on your touchtone phone. If you are using a speakerphone, please pick up your handset before pressing the key. If at any time your question has been addressed and you would like to withdraw your question, please press star then 2.
Brian: We will now begin the question and answer session.
Speaker Change: To ask a question you May Press Star then one on your Touchtone phone.
Brian: If youre using a speakerphone please pick up your handset before pressing the keys.
Brian: If at any time. Your question has been addressed and you would like to withdraw your question. Please press Star then two.
Operator: At this time, we will pause momentarily to assemble our roster.
Brian: At this time, we will pause momentarily to assemble our roster.
Jonathan Chang: The first question today comes from Jonathan Chang with Lee Ring Partners. Please go ahead.
Speaker Change: The first question today comes from Jonathan Chang with Leerink Partners. Please go ahead.
Yander Li: Hi, this is Yander Li for Jonathan Chang. Thanks for taking my question.
Speaker Change: Hi, This is younger Li on for Jonathan Chang. Thanks for taking my question. So the first question I have is that could you share. The latest progress on how you are mitigating b a S. D O T elevation and proteinuria issue related to Emily and how do you think that might increase.
Yander Li: So the first question I have is that, could you share the latest progress on how you are mitigating the ASDLT elevation and protein urea issue related to Emily? And how do you think that might increase your confidence in maintaining the dose intensity at a higher dose level?
Speaker Change: Your competence in maintaining the dose intensity at the higher dose level. Thank you.
Martin Huber: Thank you for the question. I'll start with the AST, then go into the proteinuria, and then get your last question. So, with regards to AST, AST does not result in meaningful amounts of dose delays, and even if a patient does have a delay, it's only about a week. So, at this point in time, AST is a transient, reversible phenomena that is not having a meaningful impact on our ability to deliver dose. With regards to proteinuria, just to reiterate, that is primarily a challenge or leading to dose delays only at the highest dose rate.
Speaker Change: Thank you for the question I'll start with the ASC that joined the proteinuria.
Speaker Change: Your last question so with regards to a S. T. A S. T does not result in meaningful amounts of dose delays.
Speaker Change: And even if a patient does have a delay it's only about a week. So at this point in time a S. T is a transient and reversible phenomena that is not having a meaningful impact on our ability to deliver does.
Speaker Change: With regards to proteinuria just to reiterate that is primarily a challenge or leading to dose delays only at the highest doses dose range. So what we're currently doing is as we mentioned we had an amendment to the protocol, which.
Martin Huber: So, what we're currently doing is, as we mentioned, we've had an amendment to the protocol, which does several things. One, it puts in place mitigation, such as ACE inhibitors and ARBs early, in a kind of a prophylactic manner, to minimize the development of proteinuria. But importantly, in the setting of when proteinuria does occur, but it is asymptomatic, in that a patient is not having edema, not having, they're not having any serum hypoalbuminemia or serum creatinine changes. For those patients, we're able to maintain dosing by doing a dose reduction as opposed to a dose delay. So, we look forward to testing that in the clinic to show that we are able to maintain dose intensity.
Speaker Change: Does several things one it puts in place mitigation, such as Ace inhibitors or arbs.
Speaker Change: Early in a kind of a prophylactic manner.
Speaker Change: To minimize the development of proteinuria, but importantly.
Speaker Change: As in the timing of when proteinuria does occur, but it is a symptomatic in.
Speaker Change: Is that a patient is not having a deemed them not having theyre not having any serum hydro all behavior of serum creatinine changes for those patients were able to maintain dosing.
Speaker Change: I'm doing a dose reduction as opposed to a dose delay. So we are we look forward to testing that in the clinic to show that we are able to maintain dose intensity.
Yander Li: The Clinical Outcome will... We're doing the experiment now. Got it.
Speaker Change: The clinical outcome will we're doing the experiment now.
Speaker Change: Got it and just a quick follow up on the protein you Yeah, I think on the separate codes.
Yander Li: Just a quick follow-up on the protein urea. I think on the separate code, you did mention that it was related to podocytopathy. And do you think that's caused by B7H4 on target or off-target effect?
Speaker Change: <unk> mentioned that it wasn't related to produce cytopathology and using that caused by a pizza much for on target or off target effects just curious.
Martin Huber: Just curious about the mechanism. Thank you. We don't, at this point in time, we believe it is off-target. Other orosatin payloads that are not for B7H4 have been observed to have albuminuria, this same type of podocyte effect.
Speaker Change: Thank you.
Speaker Change: We don't at this point in time, we believe it is off target.
Other.
Speaker Change: Or is that an payloads that are not for b seven H four have been observed to have albuminuria. The same type of potent side effect.
Speaker Change: Got it thanks for taking my question.
Charles Hsu: The next question comes from Charles Hsu with Lifesci Capital. Please go ahead. Hey, good morning, everyone. Thanks for taking our questions for the call and hope everyone had a great weekend. Regarding your dose expansion criteria of having patients with one to four prior lines. What's your sense of the distribution of patients that you might be getting that have fewer, call it one to two, as opposed to more, call it three to four prior lines of therapy? I think it's too early to get that read. I mean, we opened it in the study and we're still gathering data, so I think it would be premature for me to give guidance on what we think are the lines that are actually going to be in the population.
Charles <unk>: The next question comes from Charles <unk> with lifestyle capital. Please go ahead.
Charles <unk>: Hey, good morning, everyone. Thanks for taking our questions for the colon hope everyone had a great weekend.
Charles <unk>: Regarding your dose expansion criteria of having patients with one to four prior lines of therapy. What's your sense of the distribution of patients that you might be getting that has you were call. It one to two as opposed to more call. It three to four prior lines of therapy. Thank you.
Charles <unk>: I think it's too early to get that read I mean, we opened it in this study add it we're still gathering data. So I think it would be premature for me to give guidance on what we think are the lines that are actually going to be in the population.
Charles Hsu: One thing we can't clearly say is... per inclusion-exclusion criteria, those patients who had previously been on with 5, 6, or 7 are excluded from the program. So at a minimum, it will ensure that patients don't have more than four. That is part of the program. Got it. Great. Thank you for that.
Charles <unk>: One thing I would say one thing we can clearly say is.
Charles <unk>: Her inclusion exclusion criteria dose patients who had previously been on with five six or seven are excluded from expansion. So at a minimum it will ensure that patients don't have more than four prior lines.
Charles <unk>: That is part of the protocol.
Charles <unk>: Got it great. Thanks. Thank you figure that maybe one quick follow up right now.
Charles Hsu: Maybe one quick follow-up right now. I think you went through this a little bit as well, but, you know. To what extent... will your second dose, your second go-forward dose, the identification of that be dependent, you know, on your ability to mitigate proteinuria? So you've already selected 67.3 in the intermediate range. And is there a scenario where you go for something, let's call it, in the middle to the higher end of your high dose range if your proteinuria mitigation works very well? Or is there an alternative scenario where you could end up maybe selecting even a separate dose beyond?
Charles <unk>: I guess, then you know like them.
Thank you went through this a little bit as well, but you know.
Charles <unk>: To what extent.
Charles <unk>: Will your second dose your second go forward dose the identification of that'd be dependent on your ability to mitigate proteinuria. So you've already selected 67 three in the intermediate range and is there.
Charles <unk>: Scenario, where you go for something let's call. It in the middle to the higher end of your high dose range, if you're protein urea mitigation works very well or is there an alternative scenario, where you could end up maybe selecting even separate dose beyond that thank you.
Charles <unk>: Well at this point in time, we are studying doses up to 95 milligrams per meter squared.
Charles Hsu: At this point in time, we are studying doses up to 95 milligrams per meter squared. We are, so we are not exploring anything higher than that at this. Thank you for taking the time.
Charles <unk>: Ill.
Charles <unk>: So we're not exploring anything higher than that at this point in time.
Charles <unk>: Thank you for taking the questions.
Operator: As a reminder, if you have a question, please press star then 1 to be joined into the question queue.
Speaker Change: As a reminder, if you have a question. Please press star then one to be joined into the question queue.
Michael Schmidt: The next question comes from Michael Schmidt with Guggenheim. Please go ahead. Hey, good morning. Thanks for taking our questions. This is Paul. I'm from Michael.
Speaker Change: The next question comes from Michael Schmidt with Guggenheim. Please go ahead.
Speaker Change: Good morning, Thanks for taking our questions. This is Paul on for Michael.
Paul: I wanted to expand a bit on how you're currently thinking about establishing the final biomarker cutoff. Is it reasonable to expect wherever you land on TPS score to still capture roughly half of the TNBC population, or could there still be a meaningful swing factor in how you're thinking about B7H4i? I think while we continue to explore it, I would be surprised if it's outside of that 40% plus or minus rate, you know, 40 to 50 at the upper limit is, is. Most likely, where we'll end up, it would be, to me, it would be very surprising if we end up with more than 50, more than 50, or substantially less than 50.
Speaker Change: Wanted to expand a bit on how you're currently thinking about establishing the fire final biomarker cutoff.
Speaker Change: No both expect wherever you land on TPS score just don't capture roughly half of that.
Speaker Change: CNBC population.
Speaker Change: Will be a meaningful swing factor and how youre thinking about would be some need for high.
Speaker Change: Yes.
Speaker Change: While we continue to explore it.
Speaker Change: Would be surprised if it's outside of that 40% plus or minus range.
Speaker Change: 40 to 50 of the upper limit is.
Speaker Change: Most likely where we'll end up.
Speaker Change: To me it would be very surprising if we end up with more than 50 more than 50 or substantially less than 40.
Paul: But, and with the TPS, I'm sorry, for proportion of the population, the TPS score could be That's TBD, with the actual percent, TBS, Tumor Proportion Score Number. Got it.
Speaker Change: But with a T P I'm sorry.
Speaker Change: The proportion of the population the TPS score could be.
Speaker Change: That's TBD.
Speaker Change: The actual percent GBS tumor proportional score number is.
Speaker Change: Got it and then just as a follow up just can you set some expectations for the phase.
Jason Fredette: And then, just as a follow-up, just can you set some expectations for the updated base 1 dose escalation and backfill data later this year, which dose levels are in focus for enrollment, how many additional patients of data we potentially see, and what's the sort of gating factor for when you'll be ready to provide that update? Thank you. Yeah, this is Jason. We haven't defined that. What we've said is we plan to present additional escalation and backfill data later on this year, as Marty alluded to. You know, we're looking at doses up to 95 mgs per meter squared.
Speaker Change: Today's one dose escalation and backhaul data later this year, which dose levels are in focus for enrollment how many additional patients of data can we potentially see and what's the sort of gating factor for when you'll be ready to provide an update thank you.
Speaker Change: Yes.
Speaker Change: This is Jason we haven't defined that what we've said is we plan to present additional escalation and backfill data later on this year as Marty alluded to.
Speaker Change: We're looking at doses up to 95 <unk> per meter squared.
Andy Shea: But we haven't defined how much incremental data would be in that, in that The next question comes from Andy Shea with William Blair. Please go ahead. Great, thanks for taking our questions. Just one quick one for us. Just looking at the updated deck, I think the only thing that changed is the competitive landscape.
Speaker Change: But we haven't defined how much incremental data would be in that and that readout.
Speaker Change: Yeah.
Speaker Change: The next question comes from Andy Shay with William Blair. Please go ahead.
Speaker Change: Yeah.
Speaker Change: Okay, great. Thanks for taking my questions. Just one quick one for US just looking at the updated deck, Andy the only thing that changes the competitive landscape Marty I think you mentioned a little bit in your prepared remarks about about.
Martin Huber: Marty, I think you've mentioned a little bit in your prepared remarks about the evolving competitive landscape, but I'm curious if you can kind of dive in deeper about some of the competitors. Phase 3 dropped out, just, you know, hoping to hear a little bit more from you. Thank you.
Speaker Change: About the evolving competitive landscape, but I'm curious if you can kind of dive in deeper about some of the competitors.
Speaker Change: Phase III dropped out.
Speaker Change: Hoping to hear a little bit more for me. Thank you.
Brian DeSchuytner: I'm going to let Brian give you a more detailed answer on that one. Yeah. As Marty articulated, we believe that EMILY is very well positioned in the B7H4 space. As you noted with the departure of one of our competitors, we're the most advanced for statin B7H4 development. We're the only company that has shared initial positive efficacy data in that post-op breast cancer setting. As you remark, one competitor is moving into pivotal studies in a gynecologic tumor. I think we feel like this is very encouraging because it's an additional validation that you can see meaningful activity on that target.
Speaker Change: Yeah, I'll, let Brian give you a more detailed answer on that one yeah as Marty articulated we believe very well positioned in the <unk> space.
Speaker Change: As you noted with the AD the departure of one of our competitors. We are the most advanced or statin B seven H for development are the only company that is shared.
Speaker Change: Our initial positive efficacy data that puts total breast cancer setting.
Speaker Change: As you remark one competitors moving into pivotal studies in a gynecologic tumor.
Speaker Change: And feel like this is very encouraging because it is additional validation that you can see meaningful activity on that on that target.
Brian DeSchuytner: But several topo competitors very much focused on ovarian and endometrial at this stage. So we believe, one, in EMILY's potential as monotherapy. We also believe that our safety and tolerability profile may afford us an opportunity to combine with things like platinum chemo and other ADCs. And we think long-term, as a set of development opportunities, some of our competitors might be very challenged to pursue those combinations. And so I think as we look at the overall competitive landscape, we view it very favorably.
Speaker Change: But.
Speaker Change: Several co towboat competitors very much focused on on ovarian and endometrial at that at this stage. So should we believe one in emily's potential as monotherapy. We also believe that our safety and Tolerability profile may afford us an opportunity to combine with things like platinum chemo and others.
Speaker Change: D season, and we think long term.
Speaker Change: As a set of development opportunities some of our competitors might be very challenged to pursue those combinations and so I think as we look at the overall competitive landscape, we view it very favorably.
Asthika Goonewardene: The next question comes from Asthika Goonewardene with Truist. Please go ahead. Hey, good morning, guys. Thanks for taking my questions. Two quick ones, if I may.
Speaker Change: The next question comes from the S ticket goon awarding with the truest. Please go ahead.
Speaker Change: Hey, good morning, guys. Thanks for taking my questions two quick ones, if I may could.
Asthika Goonewardene: Could you give us a little bit of clarity on when we could expect some of the expansion cohort data to 67 migs? And then when you presented data earlier this year, we looked at three different intervals, the Q3, the Q4, and then a two-on, two-off. I'm curious if you're looking at other intervals, maybe like a three-on, one-off, or any other types of other formats as well, just to kind of clutch on the dosing. Thanks.
Speaker Change: Could you give us a little bit of clarity on when we could expect some of the expansion cohort data to 67, Megs and then.
Speaker Change: When you presented data early this year, we looked at three different intervals. The Q3 to Q4 and then two on two off.
Speaker Change: I'm curious if you are looking at other intervals, maybe like a three on one off or any other types of other formats as well just to kind of extended the collection the dosing. Thank you.
Martin Huber: This is Marty. I'll answer the second one first. At this point in time, we are not studying any schedules beyond what we previously shared. We are continuing to explore different schedules at this point in time, but they're limited to the three we've already shared. And with regards to expansion, we are not giving any further details on timing of expansion, other than to say that we are continuing to enroll patients, and investigators remain enthusiastic about the study.
Marty Huber: It's Marty I'll answer the second one first.
Marty Huber: At this point in time, we are not study any schedules beyond what we previously shared.
Marty Huber: We are continuing to explore different schedules at this point in time, but they are limited to the three we've already shared.
Marty Huber: And with regards to expansion, we are not giving any further details on timing of expansion other than to say that we are continuing to enroll patients and investigators remain enthusiastic about the study.
Colleen Kusy: The next question comes from Colleen Kusy with Baird. Please go ahead. Hey, y'all.
Speaker Change: The next question comes from Colin <unk> with Baird. Please go ahead.
Marty Huber: Okay.
Nick: This is Nick on for Colleen. Thanks for taking our question.
Marty Huber: Oh this is Nick on for Colin Thanks for taking our question. So for <unk> 2056, just wanted to ask what you have to show on the PD update and if there's a ballpark on how many patients or how much follow up you might have and if we can might see any early efficacy efficacy data at that time as well.
Martin Huber: So for XMT 2056, just wanted to ask what you have to show on the PD update, and if there's a ballpark on how many patients or how much follow-up you might have, and if we might see any early efficacy data at that time as well. We're not going into any detail beyond the fact that our primary objective will be to share pharmacodynamic data showing that we're getting activation of the same pathway in HER2-positive tumors. As far as any other details, we're not sharing.
Marty Huber: We're not going into any detail beyond the fact that our primary objective will be to share pharmacodynamic data showing that we're getting activation of the sting pathway.
Marty Huber: In her two positive tumors as far as any other details we're not sharing it at this point in time.
Operator: As a reminder, if you have a question, please press star, then 1, to join the question queue.
Marty Huber: As a reminder, if you have a question. Please press Star then one to join the question queue.
Justin Zelin: The next question comes from Justin Zelin with BTIG. Please go ahead. Great. Thanks for taking the question.
Justin Zelman: The next question comes from Justin Zelman with P. T. I G. Please go ahead.
Justin Zelman: Great. Thanks for taking the question. This is jeet on for Justin.
Jidon: This is Jidon for Justin. I believe you had said you're going up to 95 mg per meter squared, but I do believe there was a 115 mg dose. Was there any reason why 115 isn't being explored further? And will we see a meaningful number of patients with proteinuria mitigation as part of this year's update? Well, I think, well, first of all, we are not studying 115 any further. At the 115 dose, we did observe the, we saw it was reversible, but we did see grade 3 AST in two of the three patients. And while we could have potentially explored that further, we made the decision that we were not going to, because we were getting the exposures we were targeting at 95 and below.
Speaker Change: I believe you had said you're going up to 95 <unk> per meter squared, but I do believe there was a $1 15, Meg dose was there any reason why $1 15 isn't being explored further and will we see a meaningful number of patients with proteinuria mitigation as part of this year's update.
Speaker Change: Well I think well first of all we are not study $1 15 any further.
Speaker Change: The 150 dose we did observe the we saw it was reversible, but we did see grade three a S T.
Speaker Change: Two of the three patients and while we could have potentially explore that further we made the decision that we were not going to because we were getting we were getting the exposures. We were targeting at 95 and below so our focus has been on a cap of the 95 every four weeks or the variations of that.
Jidon: So our focus has been on a cap of the 95 every four weeks or the variations of that. And on the second question, in terms of, again, the additional escalation and backfill data, you know, what we'll show is somewhat time-dependent, right, in terms of when we plan to share data.
Speaker Change: And then on the second question in terms of again.
Speaker Change: Additional escalation and backfill data.
Speaker Change: What will show is somewhat time dependent right in terms of when we plan to share data. So we're not providing any additional specifics at this stage.
Jidon: So we're not providing any additional specifics at this time. Got it.
Speaker Change: Got it and maybe a follow up with the Pfizer program now discontinued have you spoken to any kols, who have been on both the Pfizer study as well as yours and if so how do they compare the two agents so far thank you.
Jidon: And maybe a follow-up.
Martin Huber: With the Pfizer program now discontinued, have you spoken to any KOLs who have been on both the Pfizer study as well as yours? And if so, how do they compare the two agencies? Well, they're not going to give us details of confidential data from Pfizer. I think the main thing has been at this point in time, we had already heard from the investigators and the KOLs that Pfizer was not going to pursue their B7H4 in TNBC post-TOPA. That was known even before they discontinued the program overall. And so we were being approached by investigators to participate in our study because they have – when they heard through the grapevine, to be frank, even before our data was disclosed, because we meet with these investigators, we have them under CDAs, they looked at our data as a promising opportunity in TNBC post-TOPA, and to be frank, it was the only game in town for their patients.
Speaker Change: Well, they're not going to give us details are confidential data from Pfizer I think the main thing has bad at this point in time, we had already we had already heard from the investigators and the Kols that Pfizer was not going to pursue pursue their b seven H for.
Speaker Change: Sure Ian T N V C pulse topol that was known even before they discontinued the program overall.
Speaker Change: And so we were being approached by investigators to participate in our study.
Speaker Change: Because they have they were they basically heard.
Speaker Change: Through the great volume to be Frank even before our data was disclosed.
Speaker Change: We meet with these investigators we have them under CDA. They looked at our data as a promising opportunity at <unk> and to be Frank It was the only game in town for their patients. So that's why we had.
Martin Huber: So that's why we had – Several of those sites actively decide to join our study. As far as the actual data that Pfizer had in this population, they did not share that with us, once again, other than to state that Pfizer was not pursuing.
Speaker Change: Several of those sites actively decide to join our study.
Speaker Change: As far as the actual data the advisor had in this population they did not share that with us once again other than to state that Pfizer was not pursuing this indication.
Operator: This concludes our question and answer session.
Speaker Change: This concludes our question and answer session I would like to turn the conference back over to CEO, Dr. Marty Huber for any closing remarks.
Martin Huber: I would like to turn the conference back over to CEO Dr. Marty Huber for any closing remarks. Thank you, Operator, and thanks, everyone, for dialing in. We'll look forward to seeing many of you at the TD Cowan Healthcare Conference here in Boston tomorrow, as well as at Larynx Healthcare Conference in Miami next week.
Speaker Change: Thank you operator, and thanks, everyone for dialing in we look forward to seeing many of you at the TV Cowen Healthcare conference here in Boston Tomorrow, as well as at Leerink Healthcare Conference in Miami next week that concludes our call operator. Thank you.
Operator: That concludes our call, Operator. Thank you.
Speaker Change: Yeah.
Operator: The conference is now concluded. Thank you for attending today's presentation.
Speaker Change: The conference has now concluded. Thank you for attending today's presentation you may now disconnect.
Operator: You may now disconnect.
Speaker Change: Okay.
Speaker Change: [music].