Q3 2023 Mersana Therapeutics Inc Earnings Call
Good morning, and welcome to the first polymer Therapeutics third quarter 2023 conference call and webcast.
Speaker 1: Good morning and welcome to the Marzano therapeutic third quarter 2023 conference call and webcast. Currently all participants.
Currently all participants are in listen only mode.
Speaker 1: There will be a question and answer session at the end of this call. Please note the call.
There will be a question and answer session at the end of this call.
Please note this call is being recorded.
Speaker 1: I would now like to turn the call over to Jason Pradek, Senior Vice President, Investor Relations, and Corporate Communications. Thank Onh?hail Amazephi and Honólizhi Abhinal Malang sesha taita thai thai thai-heartaiad plisaibh??.
I would now like to turn the call over to Jason Fredette, Senior Vice President Investor Relations and corporate communications.
Please go ahead.
Speaker 2: Thank you operator and good morning everyone. Before we begin, please note that this call will contain forward-looking statements within the meeting of federal securities laws.
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 our platforms product candidates business strategy clinical trial execution and results business development efforts and cash.
Speaker 2: These statements may include, but are not limited to those related to our platforms, product candidates, business strategy, clinical trial execution and results, business development efforts.
Speaker 2: 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. These risks and uncertainties are discussed in our quarterly report on Form 10Q filed with the Securities and Exchange Commission on August 8, 2023 and in subsequent SEC filing.
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 August eight 2023 and in subsequent SEC.
Pilings, our filings are available at SEC Gov, and on our website Marsano dotcom, except as required by law, we assume no obligation to update forward looking statements publicly even if new information becomes available in the future.
Speaker 2: Our filings are available at fcc.gov and on our website, mersthonna.com. Except it's required by law, we assume no obligation to update for looking statements publicly, even if new information becomes available in the future.
Speaker 2: On the call today, we have Mersana's President and Chief Executive Officer, Dr. Marty Huber, and our Chief Operating Officer and Chief Financial Officer, Brian Deschaitner. With that, let me turn the call over to Marty to begin our discussion.
On the call today, we have <unk>, President and Chief Executive Officer, Dr. Marty Huber, and our Chief operating Officer, and Chief Financial Officer, Brian to Shatner with that let me turn the call over to Marty to begin our discussion.
Speaker 3: Thank you Jason and good morning everyone. It's a pleasure to be speaking with you about eight weeks into my tenure as Marzana CEO . Over the course of these two months, many investors and analysts have asked why I chose the role. So let's start there. It's really because of our people, platforms, product candidates, and our financial position.
Thank you, Jason and good morning, everyone. It's a pleasure to be speaking with you about eight weeks into my tenure as Marsano C V go.
Of course, these two months many investors and analysts type ask why I chose the wrong. So let's start there.
It's really because of our people platforms product candidates and our financial position.
Having served as a board member since 2020, and having worked with several of our executives in a prior role I knew this was a high caliber phi-function team. It was driven by a mission to make a real difference for patients.
Speaker 3: Having served as a Marissa on a board member since 2020 and having worked with several of our executives in a prior role, I knew this was a high caliber, high functioning team that was driven by a mission to make a real difference for patients.
Speaker 3: In addition, my role as a director provided a clear view that from an innovation standpoint, we had advanced well beyond DOLA Flexon, our first generation ADC platform, and that we were making meaningful progress with our next generation platforms, DOLA Senten, and AMITA Senten.
In addition, my role as a director provided a clear view that from an innovation standpoint, we had advanced well beyond toll flexing, our first generation ADC platform that when were making meaningful progress with our next generation platforms dullness, sometimes and sometimes.
Speaker 3: Not only that, but thanks in part to the difficult decisions that were made in the wake of uplift, we also have a balance sheet providing an opportunity to accomplish our objectives.
Not only that but thanks in part to the difficult decisions that were made in the wake of uplift. We also have a balance sheet, providing an opportunity to accomplish our objectives.
Speaker 3: By time, the CEO role has only strengthened my conviction about these factors and my excitement about personas potential.
My time in the CEO role has only strengthened my conviction about these factors and my excitement about where some of those potential.
Speaker 3: Now, let's move on to our core areas of focus. The first is XMT 1660, which was developed utilizing DolosVinvent, our next generation cytotoxic ADC platform.
Now, let's move on to our core areas of focus.
The first is <unk> 16, 6 billion, which was developed utilizing Dulles center.
Our next generation cytotoxic ADC platform.
Speaker 3: Our pre-clinical work has shown that Dolosinthin has numerous potential advantages over Dolos flexing. Our first generation ADC platform that was utilized to develop upreaks.
Our preclinical work has shown that told us that that has numerous potential advantages over Doe will flex with our first generation ADC platform that was utilized to develop outbreak.
Speaker 3: Like many first generation platforms, dolaflexin produced a heterogeneous population of ADCs. Published data from other platforms have shown that some species within heterogeneous ADC mixtures, specifically hydrophobic high DAR subpopulations, can negatively impact safety and tolerability while having limited to no contribution in terms of efficacy.
Like many first generation platforms don't want flex and produced a heterogeneous population of agencies published data from other platforms have shown that some species within heterogeneous ADC mixtures.
Typically hydrophobic high Dar subpopulations can negatively impact safety and Tolerability, while having limited to no contribution in terms of efficacy.
Speaker 3: We spent years developing a technology that improved upon both first-gen platforms and bill of flexion. Specifically, we wanted the ability to identify an ADC alpha-former and then produce that alpha-former in a completely homogeneous fashion.
We spent years developing a technology that improved upon first gen platforms.
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Specifically, we wanted the ability to identify and ADC outperformer, and then produce stat out performer in a completely homogeneous fashion.
Speaker 3: We believe this would result in improved drug-like properties, the potential for enhanced efficacy, and further reduction in off-target toxicity. Additionally, we wanted the ability to optimize both drug to antibody ratios and site-specific conjugation approaches. Dolas-Syntin is the result of that effort.
We believe this would result in improved drug like properties the potential for enhanced efficacy.
And further reduction in off target toxicity.
Additionally, we wanted the ability to optimize bow drug to antibody ratios and site specific conjugation approaches Dolan symptom is the result of that effort.
Speaker 3: across preclinical models when we compare Dolosin to ADC to those from Doloslexin and first-gen platforms like BCMMAE, we see clear benefits in terms of pharmacokinetics, tumor delivery, efficacy, and toxicity.
Across preclinical models, when we compare dulles at that ADC from Dol flex them in first Gen platforms like E. M. M E. We see clear benefits in terms of pharmacokinetics tumor delivery efficacy and toxicity.
X M. T 16, 16, our lien documents have been ADC now provides a near term opportunity to demonstrate these advantages clinically.
Speaker 3: XMP 1660, our lead, Dolor 780C, now provide a near-term opportunity to demonstrate these advantages clinically.
Speaker 3: XMT 1660 is a DAR 6 ADC targeting B7H4, a member of the B7 family of immune checkpoint markers that's been shown to have limited expression in healthy tissue and over expression in multiple tumor types with high unmet medical need including breast, ovarian and endometrial cancer.
<unk> is a dart six ADC targeting <unk> seven age for a member of the <unk> family of immune checkpoint markers. That's been shown to have limited expression in healthy tissue and over expression in multiple tumor types with high unmet medical need including breast ovarian and endometrial.
Cancers.
Speaker 3: At ESMO last month, initial clinical data were shared by others in the field, helping to validate B7H4 as an intriguing target.
At ESMO last month initial clinical data was shared by others in the field, helping to validate <unk> seven H for as an intriguing target.
Speaker 3: In light of these early data, we believe there are opportunities to differentiate XMT1660 from others in this space.
In light of these early data we believe there are opportunities to differentiate X 17, 16 16 from others in this space.
Speaker 3: We continue to advance 1660 in the dose escalation portion of our phase one trial.
We continue to be at $60 60 in the dose escalation portion of our phase one trial.
Speaker 3: Additionally, we have begun to enroll patients in backfill cohorts at clinically relevant doses as part of our dose escalation design. By the end of this year, we expect to complete dose escalation with dose expansion planned for 2024.
Additionally, we have begun to enroll patients and backfill cohorts at clinically relevant doses as part of our dose escalation design.
By the end of this year, we expect to complete dose escalation with dose expansion planned for 2024.
It also it's worth noting that we have been making good progress in our collaboration with Janssen that.
Speaker 3: It also is worth noting that we have been making good progress in our collaboration with Janssen that focuses on discovering novel, so-resensitive ADCs for up to three targets.
Since I'm discovering novel Dolan sent that ADC for up to three targets.
Janssen has shared publicly that it shows don't want something we.
Speaker 3: Jackson has shared publicly that it shows door-assistant following a comprehensive review of the ADC landscape.
With a comprehensive review of the ADC landscape.
Speaker 3: Now let's move on to XMT 2056 and in the center. As many of you know, the ADC field has focused almost exclusively on attacking tumors with cytotoxic payloads for the past two decades.
Now, let's move on to <unk> 2056 aluminum center.
Many of you know the ADC field has focused almost exclusively on attacking tumor cytotoxic payloads for the past two decades.
Speaker 3: Several years ago, we began to explore how we might be able to leverage the benefit of an ADC approach to activate an innate immune response selectively in the tumor microenvironment.
Several years ago, we began to explore how we might be able to leverage the benefits of an ADC approach to activate an innate immune response selectively in the tumor microenvironment.
Speaker 3: Immunicentin is the result of this effort. Immunicentin is an entirely unique platform that leverages a sting agonist payload with the goal of activating sting signaling in both tumor resident immune cells and in antigen expressing tumor cells.
Immuno syndrome is the result of this effort.
I mean, a citizen is an entirely unique platform.
Leverages, a sting agonist payload with the goal of activating distinct signaling.
Tumor resident immune cells, and an antigen expressing tumor cells.
Speaker 3: We initiated a Phase I clinical trial of XNT 2056, our first immunocentin ADC candidate earlier this year. This trial was placed by clinical hold, following a grade five adverse event in one of the initial patients that I've been doing.
We initiated a phase one clinical trial of X M. T 2036, our first immuno sits in ADC candidates earlier this year.
This trial was placed on clinical hold following a great five adverse events and one of the initial patients that had been dosed.
This served as an unfortunate reminder, that when developing truly novel mechanisms. The translation from preclinical to clinical can sometimes be less predictable.
Speaker 3: This served as an unfortunate reminder that when developing truly novel mechanisms, the translation from preclinical to clinical can sometimes be less predictable.
We don't deeply into cytokines pharmacokinetics and other clinical data from the patients dosed in this trial.
Speaker 3: We go deeply into cytokine, pharmacokinetic, and other clinical data from the patients that has been this trial.
Speaker 3: The findings from the initial patients does in our phase one clearly indicated that XMP 2056 is a much more potent in the stimulator in humans than we've seen pre-clinically.
The findings from the initial patients dosed in our phase one clearly indicated that X M. T 2056 is a much more potent.
Stimulator in humans than we'd seen pre clinically.
Speaker 3: As a result, we developed a response to the FDA that included a lower starting dose in our phase one dose escalation, divide.
As a result, we developed a response to the FDA that included lower starting dose in a phase one dose escalation Dubai.
We were very pleased to share the news last week that the clinical hold on the phase one trial of <unk> 2056 have been lifted by the FDA.
Speaker 3: We were very pleased to share the news last week that the clinical hold on the phase one trial of X MT-2056 has been lifted by the FDA. Our kitchen has now turned to re-engage in the clinical sites to reinitiate and roll.
Our attention has now turned to reengage them with clinical sites to Reinitiate enrollment.
Speaker 3: And finally, I would also like to mention that our analysis of the results from uplift and ovarian cancer is nearly in its completion. We plan to present the data at a medical meeting during the first half of 2024.
And finally I would also like to mention that our analysis of the results from uplift in ovarian cancer is nearing its completion, we plan to present the data at medical meetings during the first half of 2024.
In summary, I'm proud of all the recent progress that has been made by the Barcelona team and my excitement about what lies ahead for the company continues to build.
Speaker 3: In summary, I'm proud of all the recent progress that has been made by the mercenacine. And my excitement about what lies ahead to the company continues to build.
Speaker 3: The highly differentiated platforms and clinical stage molecules, strong collaborations, a great team, and a healthy balance sheet. persona has an opportunity to make a difference for patients with a range of cancers. And we are working hard to-
With highly differentiated platforms and clinical stage molecules strong collaboration.
Great team and a healthy balance sheet first of all I don't have an opportunity to make a difference for patients with a range of cancers.
And we are working hard to deliver on this promise we look forward to sharing more with you about our outlook for 2024 and key upcoming milestones in January.
Speaker 3: We look forward to sharing more with you about our outlook for 2024 and key upcoming milestones in January . With that, let's turn things over.
With that let's turn things over to you Brian.
Speaker 3: Thank you, Mari. Let me begin this portion of the call with a brief update on the restructuring and reprioritization actions we've been out in July . These actions included a workforce reduction of approximately 50% and a wind-down of up-rerelated development activities. I'm pleased to report that the vast majority of our workforce reduction is already complete and that the remainder of our restructuring and up-re-bind-down efforts will be substantially completed by the end of the year.
Thank you Marty let me begin this portion of the call with a brief update on our restructuring and re prioritization actions we've been out in July.
These actions included a workforce reduction of approximately 50% and a wind down of our pre related development activities. I am pleased to report that the vast majority of our workforce reduction is already complete and that the remainder of our restructuring an up REIT bind out efforts will be substantially completed by the end of the year. This will set us up for a meaningfully.
Speaker 3: This will set us up for a meaningfully simplified cost structure in 2024.
Simplified cost structure in 2024.
Speaker 3: We ended the third quarter of 2023 with approximately $241 million in cash equivalents and marketable securities, which compares with the balance of approximately $281 million as of the end of 2022. Thanks in part to our restructuring and reprioritization efforts. We expect our available funds to support our operating plan commitments into 2026.
We ended the third quarter of 2023 with approximately $241 million in cash cash equivalents and marketable securities, which compares with a balance of approximately $281 million as of the end of 2022. Thanks in part to our restructuring and re prioritization efforts, we expect our available funds to support our off.
Operating plan commitments into 2026. Please note that our cash runway guidance does not assume any potential milestone payments from our current collaborations or proceeds that we may realize from future collaborations.
Speaker 3: Please note that our cash runway guidance does not assume any potential milestone payments from our current collaborations or proceeds that we may realize from future collaborations.
Turning to the income statement I would like to begin with a reminder, that the third quarter was a time of transition from our previous business strategy that focused heavily on offering to our current strategy that focuses on our next generation platforms Accenture 60 exit to 2056 and our collaborations.
Speaker 3: Turning to the income statement, I would like to begin with a reminder that the third quarter was a time of transition from our previous business strategy that focused heavily on operating to our current strategy that focuses on our next generation platforms, XMT660, XMT2056, and our collaboration.
Speaker 3: Net cash used in operating activities was approximately $46.1 million for the third quarter of 2023.
Cash used in operating activities was approximately $46 $1 million for the third quarter of 2023 collab.
Speaker 3: Collaboration Revenue for the third quarter of 2023 with $7.7 million compared to $5.6 million for the same period in 2022. The year of over year increased was primarily related to a greater contribution from our immune-vacented collaboration with Mark KGA.
Collaboration revenue for the third quarter of 2023, with $7 7 million compared to $5 $6 million for the same period in 2022.
Year over year increase was primarily related to a greater contribution from our music centric collaboration with Merck K G.
Speaker 3: Research and development expenses for the third quarter of 2023 were $30.5 million compared to $50.6 million for the same period in 2022. This decline was primarily related to reduced manufacturing and clinical costs related to operating in XMT 2056 and reduced employee compensation.
Research and development expenses for the third quarter of 2023 were $30 $5 million compared to $56 million for the same period. In 2022. This decline was primarily related to reduced manufacturing and clinical costs related to operating an accident 2056 and reduced employee compensation.
Speaker 3: non-cash R&D-related stock base compensation expense for the third quarter of 2023 is $2.2 million.
Noncash R&D related stock based compensation expense for the third quarter of 2023 was $2 $2 million.
Speaker 3: General administrative expenses for the third quarter of 2023 were $12.9 million compared to $14.6 million during the same period in 2022. The year over year decline was primarily related to reduced consulting and professional services and reduced employee compensation. Non-CASH G&A-related stock-based compensation expense for the third quarter of 2023 was $1.8 million.
General and administrative expenses for the third quarter of 2023 were $12 9 million compared to $14 $6 million. During the same period in 2022 the year over year decline was primarily related to reduced consulting and professional service fees and reduced employee compensation noncash G&A related to stock based compensation expense stripped third quarter.
2023 was $1 $8 million during the third quarter, we incurred $8 $2 million in restructuring charges related primarily to severance related costs and contract termination expenses <unk> net loss for the third quarter of 2023 was $41 $7 million compared to a net loss of $59 $8 million for the same period.
Speaker 3: During the third quarter, we incurred $8.2 million of restructured charges related, primarily to statements related to class and contract termination expectations.
Speaker 3: RISANA's net loss for the third quarter of 2023 was $41.7 million compared to a net loss of $59.8 million for the same period in 2022. That concludes our business update. Operator, will you please open the call to questions from the audience.
2022.
That concludes our business update operator will you. Please open the call to questions from the audience.
We will now begin the question and answer session.
Speaker 1: to ask a question, you may pre-starve in one on your touchtone phone. To withdraw your question,
To ask a question you May Press Star then one on your Touchtone phone.
With your question. Please press Star then two.
Speaker 1: At this time we will pause momentarily to assemble our roster.
At this time, we will pause momentarily to assemble our roster.
Speaker 1: And our first question will come from Jonathan Chang, a We-Rank partners. Please go ahead.
And our first question will come from Jonathan Chang of Leerink Partners. Please go ahead.
Speaker 4: Good morning and thanks for taking my questions. First question, can you give us a sense of when we might see initial XMT 1660 clinical data and second question, the comment about enrolling patients in Baxal cohorts for 1660 can give us some color around that, how is enrollment progressing on the study and are you still doses clear?
Good morning, and thanks for taking my questions. First question can you give us a sense of when we might see initial accident. She 16 60 critical data and second question.
Comment about enrolling patients and backfill cohorts for <unk> can you give us some color around that how is enrollment progressing on the study and are you still dose escalating. Thank you.
Speaker 3: Thank you, Jonathan. We're making good progress in the dose escalation phase of the trial and have begun to enroll these patients in the backfill cohorts. What I'd like to point out is the design of this, while we're not getting into details, is consistent with other standard kind of phase one designs now where you expand the group of patients at a dose or doses in order to get a better understanding for your recommended phase two dose.
Thank you Jonathan.
We're making good progress in the dose escalation phase of the trial.
And have begun to enroll these patients and the backfill backfill cohorts what I'd like to point out is the design of this is what we're not getting into details is consistent with other standard kind of phase one designs now where you expand the group of patients at a rate at a dose or doses in order to get a better understanding for your recommended phase two.
Speaker 3: Importantly, these patients are the same population as we're enrolling in the study, which is restricted to a set of patients with TNBC, hormone receptor positive breast cancer, and other specific tumor types.
Dose importantly beef.
<unk> patients are the same population as we're enrolling in the study which is restricted to a subset of patients with TMT a hormone receptor positive breast cancer.
Other specific tumor types.
Speaker 3: What we plan to share is a robust data set that will help differentiate XMT 1660 within the broader B7H4 landscape. We plan to share our specific goals on that, 2424 and the milestones in January . We plan to share our specific goals on that, 2424 and the milestones in January .
We plan to share is a robust dataset that will help differentiate the <unk> 16 60 within the broader beef seven H for landscape, we plan to share our specific goals on that 24 24.
Biosolids in January.
Understood. Thanks for taking the questions.
Yes.
Speaker 1: The next question comes from Colleen. To the of Ferd, please go ahead.
The next question comes from Colleen Tuesday of Baird. Please go ahead.
Speaker 5: Great, thanks. Good morning. Things are taking our questions and congrats on the progress. In the XMT 1660 study, I know you've done some work on expression level of B7H4 in different tumor types. Are you measuring B7H4 expression in the patient's enrolled in the study? And would that biomarker data be available whenever you report initial data?
Great. Thanks, Good morning, Thanks for taking my questions and congrats on the progress and the X M. T 16 to 60 30, I know you've done some work on expression level B seven H four different tumor types are you measuring b 784 expression and the patients enrolled in the study and where that biomarker data to be available whenever you report initial data next year.
Speaker 3: We are collecting data on B7H4 expression. We are importantly, we are not selecting patients, though, on B7H4 expression. So it's all patients regardless of the level of expression. With regards to reporting of that data, we are, it's certainly a factor we're considering, but at this point in time, we're giving no further details on exactly what will be in our disclosure.
We are collecting data on <unk> four expression.
Importantly, we are not selecting patients, though on <unk> four expression. So it's all patients regardless of the level of expression.
With regards to reporting of that data we are at.
Certainly a factor we're considering but at this point in time, we're giving no further details on exactly what will be at our disclosure.
Speaker 5: That's helpful, thank you. And on XMT 2056, just after all the work you've done and the data you've been able to gather, can you talk a little bit more about your latest understanding of what caused the patient death? And can you talk a little bit about the next steps between the recent lift of the clinical hold and then restarting of the enroll?
That's helpful. Thank you and an excellent 2056, just after all the work you've done on the data you've been able to gather can you talk a little bit more about your latest understanding of what caused the patient deaths and can you talk a little bit about the next steps between the recent lift the clinical hold and then restarting up that enrollment.
Sure.
Speaker 3: Sure. Well, what we did is we looked deep into our, you know, what we had to the side of time data, we looked at our pharmacokinatics, and essentially we crossed the board for the clinical data, as well as in comparison to our pre-clinical data.
Well, what we did is we look deeply.
What we have to the cytokine data, we looked at our pharmacokinetics and essentially was across the board for the clinical data as well as in comparison to our preclinical data.
Speaker 3: And one of the things we realized that XMT 2056 was a much more potent in the estimulator humans than we had thought based on the preclinical data. So while we're not going into the granular details.
And one of the things, we realized that <unk> 2056, with a much more potent immune stimulator in humans.
We had thought based on the preclinical data so while we're not going into the granular details going to a lower dose was an appropriate strategy and importantly shifts our whole way, we look at the therapeutic index.
Speaker 3: going to a lower dose was an appropriate strategy and importantly shifts our whole way we look at the therapeutic index. So, importantly, we still think we're gonna be able to achieve a positive therapeutic index and patients going forward.
Importantly, we still think we're going to be another.
Be able to achieve a positive therapeutic index of patients going forward with regards to the details as it is a amendment to the protocol. So in addition to re engaging decides to start enrolling there are some technical details when you amended protocol for <unk>.
Speaker 2: With regards to the details, it is a amendment to the protocol. So in addition to re-engaging the site to start enrolling, there are some technical details when you amend a protocol for.
Speaker 3: So do you like lab kids and things like that that you have to update as part of that and then process?
Yeah. So do you like lab kits and things like that that you have to update as part of that process.
That's helpful. Thank you and then just last one from US when you restart the there's things that are you are you changing the enrollment criteria at all.
Speaker 5: That's helpful. Thank you. And then just last one from us, when you restart the the things that you are you changing the enrollment criteria at all?
Speaker 3: The primary effect was on lowering the starting dose. There are some minimal changes, but really it's about the starting dose.
The primary factor was our lowering the starting dose there are some minimal changes but.
Really it's about the starting dose.
Great. Thanks for taking our questions.
Once again, if you would like to ask a question. Please press Star then one.
Speaker 1: Once again, if you would like to ask a question, please press star then one.
Speaker 1: And our next question will come from a sheep, the bird of city. Please go ahead.
And our next question will come from Ashish <unk> of.
Of Citi. Please go ahead.
Speaker 6: Hi guys, thanks for taking my questions. I guess maybe first you alluded to, you made some comments alluding to the idea of differentiation for your program and the B7H4 landscape. I think it might be helpful to kind of review how you're differentiated from a clinical profile perspective but also how you expect to be differentiated on a clinical development profile. Any color that would be helpful.
Hi, guys. Thanks for taking my questions I guess, maybe first you alluded to you've made some comments alluding to the idea of differentiation for your program and the piece of a niche for landscape I think it might be helpful to kind of review, how you're differentiated from our clinical profile perspective, but also how you expect to be differentiated on our clinical development profile any color that would be helpful. Thanks.
Speaker 3: Maybe I can take that. I think there's two companies that are out there in the BC 7-H4 space.
Sure, Matt maybe I can take that.
Yes, I think there's two companies.
Are out there and these have an age for space.
Speaker 3: CGen and GSK hands-off. When you think about CGen and the classical first generation ADC platform.
<unk> and GSK hand, so.
When you think about CDN and the classical first generation ADC platforms, we've compared dollars. Since then adcs versus the BC MMA adcs extensively pre clinically.
Speaker 3: We've compared Dolosinthin ADCs versus the PC, NME ADCs extensively, preclinically.
Speaker 3: and have shown frequently that our platforms can deliver payload to the tumor much more efficiently and effectively. And in addition, we've shown in our past clinical presentations that are payloads.
We've shown pre clinically that our platform can deliver payload to the tumor much more efficiently and effectively and in addition, we've shown in our past clinical presentations that are payload appears to avoid the severe neutropenia and peripheral neuropathy that that does tend to be dose limiting across MMA E programs.
Speaker 3: Here's to avoid the severe neutropenia and peripheral neuropathy that does tend to be dose limiting across MMAE program.
Speaker 3: when you move to Hanto GSK and AZ, frankly, those are all using Topo 1 payload.
When you move to the Haynesville GSK and AZ frankly, those are all using total one payloads.
Speaker 3: There's increasing evidence from conferences just this year that topo-1 pre-treated patients can develop resistance to topo payloads. And when you look at this landscape and in particular, sort of the faster market and largest opportunities in breast cancer and her two in totalalve becoming standard of care, we believe this could be a consideration.
There is increasing evidence from Congress is just this year that totaled one pretreated patients can develop resistance topel payloads and when you look at this landscape and in particular sort of a faster market and largest opportunities in breast cancer with <unk>, becoming standard of care.
We believe this could be a consideration.
Speaker 3: Frankly, I think we believe this is also evidence by some commentary about focusing on gynecologic tumors for that ADC.
And frankly I think we believe this is also evidenced by some commentary.
About focusing on gynecologic tumors for that ADC.
Speaker 3: I think another consideration is just the humanologic toxicities that you see for for total ones that are dose limiting in similar ways.
I think another consideration is just the hematologic toxicities that you see for <unk> ones that are dose limiting in similar ways.
Got it that's very helpful. Maybe one more on <unk> 2056, or obviously, reducing the dose I guess, what gives you confidence you'll be able to strike a balance between her two coverage, but not over stimulating the sting pathway, which might've course cause some immunologic safety issues I guess any color on that.
Speaker 6: That's very helpful. Maybe one more on XMT 2556, obviously reducing the dose. I guess what gives you confidence you'll be able to strike a sort of balance between her two coverage, but not overstimulating the sting pathway, which might of course cause some immunologic safety issues. I guess some color on your thoughts on the therapeutic window might be helpful here.
Thoughts on the therapeutic window it might be helpful. Here.
Bob.
Speaker 3: We're not going to go into detail here, but I think what's important is, when we look at the amount of staying agonist and the effects downstream,
We're not going to go into detail here, but I think what's important is.
When we look at the amount of staying agonist and the effects downstream.
Speaker 3: in the human systems, it's much more sensitive. So essentially the idea is that you'll shift it, but we believe that evidence of activation at the till or sell level will also be shifting as well. So that it should move, so basically the therapeutic index shouldn't fundamentally change. It just should shift to a lower dose range, but we are.
Yes.
<unk> systems, it's much more sensitive so essentially the idea is that youll shifted but we believe that evidence of activation at the tumor cell level will also be shifting as well so that it should move so basically the therapeutic index shouldnt fundamentally change it just should shift to a lower dose range.
But we are.
Speaker 3: But we're at this point in time, some of that data, we're not, I mean, we need to discuss how we're gonna have that data available. That'll be part of our January .
At this point in time some of that data, we're not I mean, we're.
We need to discuss how we're going to have that data available.
That would be part of our January discussion.
Okay got it thank you very much.
The next question comes from Calgary Pullman of BPI.
Speaker 1: The next question comes from Calvary, a woman of BPIG. Please go ahead.
Please go ahead.
Speaker 7: Yeah, good morning. Thanks for taking my questions. But can you provide any additional color on what your 2026 cash runway includes? Does it include any additional trials beyond dose expansion, 4166E, and save one for 2056?
Yeah. Good morning, Thanks for taking my questions can you provide any additional color on what your 2026 cash runway include it doesn't include any additional trials beyond those expansion or 16 six in phase one for 2056.
So I think you're correct that our cash runway guidance is based on our current operating plan commitments, which include the early clinical development of both $60 60 and 2056.
Speaker 3: So, thank you, Carrier. The Archash runway guidance is based on our current operating plan commitments, which include the early clinical development of both 1660 and 2056.
Got it and for 'twenty have T. SEC can you tell us about the hard to epitope.
Speaker 7: got it. And for 2056, can you tell us about the heart to epitope? How validated it is? And you know, progetta doesn't work well in patients are repreated with it. Is it something that's known for 2056 epitope?
It is then it doesn't work well.
Patients are treated with it is it something that's known for 2015.
<unk>.
So maybe I'll take that hurt your appetite is.
Speaker 3: So maybe I'll think that the HER2 episode is distinct from that targeted by either a pretzeman or a perceptive. But it's obviously on HER2.
From that targeted by either <unk> or herceptin.
But it's obviously on her too.
Speaker 3: It does not cross react with those sites.
It does not it does not cross react with those sites.
Speaker 7: Correct, but is it known, you know, is it known about progetta or what, you know, that it doesn't really work in patients if you retreated, whereas for septin, you can keep giving patients.
Correct, but is it known you know is it known about.
What it doesn't really work in patients that few weeks, whereas the first half and you can keep giving patients.
Yeah.
Speaker 3: even if they progress, they still respond. Is it something now? Why is that? And if your epitope has similar biology as her septum? Yep. We intentionally targeted a different her,
Even if they progress.
Great.
Is it something now.
Why is that and yet you're epitope has similar biology absolute acceptance.
We we intentionally targeted a different her.
But tobey because in principle, we should be able to target patients who have previously undergone treatment with a hurt too.
Speaker 3: the tope because the in principle there it we should be able to target patients who are previously under law treatment with a hereto there that so it it was part of the thinking was to intentionally go to a different part of the the energy.
Got it.
It was part of the thinking was to intentionally go to a different part of the the antigen.
Got it thanks for taking my question.
The next question comes from Boris <unk> of Cowen. Please go ahead.
Speaker 1: The next question comes from Boris Peaker of Cowan. Please go ahead.
Great. My first question on 16, 60 can you discuss the concept of target optimize drug to antibody ratio I just want to understand how do you know what the ideal drug to antibody ratio is for a specific target.
Speaker 8: Great. My first question on 1660. Can you discuss the concept of target optimized drug to antivariate ratio? I just want to understand how do you know what the ideal drug to antivariate ratio is for a specific target?
Speaker 3: Thank you. Well, we've done as part of a preclinical program, and this is public data, is for a given target, we create a molecule with a range of dark species. And then what we can look at, as for example, if you look at two versus dark 12 versus dark six, dark six is optimal for a given target. So this is basically experimentally derived for each one of our targets.
Bob Thank you.
What we've done as part of our preclinical program, but this is this is public data is for a given target we create a molecule with a range of <unk> to our species.
Then we can look at it is for example, if you look at our two versus dollars 12 versus our six Dr. <unk> optimal for a given target. So this is basically.
Experimentally derived for each one of our targets.
Speaker 8: And I guess for 2056, so I understand the goal to deliver the immune stimulator to the tumor microenvironment. I'm curious, is it possible somehow to tell if the activity that you're seeing is systemic in nature? Let's say the payload is coming off or just working systemically or is it actually starting in the local tumor microenvironment?
Got you and I guess.
For 2056, so I understand the goal is to deliver the immune stimulator to the tumor microenvironment I'm curious is it possible somehow to tell if the activity that youre seeing.
Stomach in nature lets say the payload is coming off or just working systemically or is it actually starting in the local tumor microenvironment.
Speaker 3: Based on the limited data we have to date, we cannot draw a conclusion on that.
Based on the limited data we have to date, we cannot draw a conclusion on that.
Great. Thank you very much for taking my questions.
Yeah.
Speaker 1: Again, if you would like to ask a question, please press star then one.
Again, if you would like to ask a question. Please press Star then one.
And our next question comes from.
Speaker 1: And our next question comes from Estica, Buonavarti of Truist, please go ahead.
Hello, Novartis of Truest. Please go ahead.
Speaker 5: Hi, this is Karina Prostika. I had a question on the B7H4 competitor data that was presented at Eizmal. Does that make you more inclined to pursue certain indications? And the mutual for example had only a 6% ORR, but this was a CR. Can you share a comment?
Hi, This is corinne across ticker I had a question on the B seven each for competitor data that was presented at ESMO.
That makes you more inclined to pursue certain indications endometrial for example had only a 6% RR, but this wasn't here can you just share color on that please.
Okay sure.
Speaker 3: Sure. I think we want to be a little careful in drawing conclusions prematurely about the specific tumor types outside of breath.
I think we want to be a little careful in drawing conclusion is pretty materially about the specific tumor types outside of breast because the numbers were fairly limited across the board. We also know in some of those some of those other tumor types. The levels of Dxp's that makes for expression may not be quite as common as it is for example.
Speaker 3: because the numbers were fairly limited across the board. We also know in some of those other tumor types, the levels of the ephenage forespression may not be quite as common, as it is, for example, in triple negative breaths.
In triple negative breast so we.
Speaker 3: So we, at this point in time, while breast cancer, especially triple negative, is probably one of the places where it's gonna be the easiest to get a clear understanding of the data. The other tumor types, we would say it's a little bit premature. We do think they're still interesting. So we still think there's an opportunity for 1660 in tumor types beyond triple negative breast.
We at this point in time, while breast cancer, especially triple negative is probably one of the places where it's got to be the easiest to get a clear understanding of the data.
The other tumor types, we would say, it's a little bit premature. We do think there is still interesting. So we still think theres opportunity for $16 60 in tumor types beyond triple negative breast.
Okay. Thank you.
Speaker 1: This concludes our question and answer session. I would like to turn the conference back over to Dr. Marty Huber for any closing remarks.
This concludes our question and answer session I would like to turn the conference back over to Dr. Marty Huber for any closing remarks.
Thank you operator, and thanks to everyone for dialing in and we hope to see some of you later this week in New York at the Truest Biopharma Symposium and I'm looking forward to keeping everyone apprised of our progress that concludes our call operator.
Speaker 3: Thank you, operator and thanks everyone for dialing in. We hope to see some of you later this week in New York at the truest biopharma symposium and I'm looking forward to keeping everyone apprised of our progress. That concludes our call operator.
Speaker 1: conferences now concluded. Thank you for attending today's presentation and you may now disconnect.
The conference has now concluded. Thank you for attending today's presentation and you may now disconnect.
Okay.
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