Q4 2023 Xencor Inc Earnings Call
Operator: Good afternoon, and thank you for standing by. Welcome to Xencor's fourth quarter and year-end 2023 conference call. At this time, all participants are in a listen-only mode.
Good afternoon, and thank you for standing by welcome to the <unk> Corp, fourth quarter and year end 2023 conference call. At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.
Operator: After the speaker's presentation, there will be a question-and-answer session. To ask a question during this session, you will need to press star 1-1 on your telephone. You will then hear an automated message advising that your hand is raised.
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Operator: To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded at the company's request. Now, I would like to turn the call over to your speaker today, Charles Liles, head of Corporate Communications and Investor Relations. The floor is yours.
Draw. Your question. Please press star one again.
Please be advised that today's conference is being recorded at the company's request now I would like to turn the call over to your speaker today, Charles Liles head of corporate Communications and Investor Relations.
The floor is yours.
Charles Liles: Thank you and good afternoon. Earlier today, we issued a press release that outlines the topics we plan to discuss today. It's available at www.xencor.com. Providing comments on the call are Bassil Dahiyat, President and Chief Executive Officer, Nancy Valenti, Chief Development Officer, and Dane Leone, Senior Vice President, Corporate Strategy. After the prepared remarks and presentation, we will then open up the call for your questions. We will then be joined by John Desjarlais, Chief Scientific Officer, and John Kuch, Chief Financial Officer. The slides that we are using today should be visible on the webcast and will be made available for download on the events and presentations page of our website.
Thank you and good afternoon earlier today, we issued a press release, which outlines the topics. We plan to discuss today is available at Www Dot Zen core dotcom, providing comments on the call about the dot yet President and Chief Executive Officer, Nancy Blotchy, Chief Development Officer, and Dane Leone, Senior Vice President corporate strategy.
After the prepared remarks and presentation. We will then open up the call for your questions and we will then be joined by John <unk>, Chief Scientific Officer, and John <unk>, Chief Financial Officer.
So we are using today it should be visible here on the webcast will be made available for download on the events and presentations page of our website.
Charles Liles: Before we begin, I would like to remind you that during the course of the conference call, Xencor management may make forward-looking statements, including statements regarding the company's future financial and operating results, future market conditions, plans and objectives of management, future operations, the company's partnering efforts, capital requirements, future product offerings, and research and development programs. These forward-looking statements are not historical facts but rather are based on our current expectations and beliefs and are based on information currently available. The outcome of the events described in these forward-looking statements is subject to known and unknown risks, uncertainties, and other factors that could cause actual results to differ materially from the results anticipated by these forward-looking statements, including but not limited to those factors contained in the risk factors section of our most recently filed annual report on Form 10-K. With that, I'll pass the call over to Bassil.
Before we begin I would like to remind you that during the course of the conference call <unk> management may make forward looking statements, including statements regarding the company's future financial and operating results future market conditions plans and objectives of management future operations. The company's partnering efforts capital requirements future product offerings and research and development programs. These forward looking statements are not historical facts.
But rather are based on our current expectations and beliefs and are based on information currently available to us.
Lucky events described in these forward looking statements are subject to known and unknown risks uncertainties and other factors that could cause actual results to differ materially from the results anticipated by these forward looking statements, including but not limited to those factors contained in the risk factors section of our most <unk>.
Recently filed annual report on Form 10-K with that I'll pass the call over to Basel, Thanks, Charles and welcome everyone. Today, we'll cover a few business highlights from 2023, we're used to working with you our clinical pipeline and provide a data update on blue dial that in prostate cancer, you can refer to our press release for more information about the last quarter and full year.
Charles Liles: Thanks, Charles, and welcome everyone. Today, we'll cover a few business highlights from 2023, briefly review our clinical pipeline, and provide a data update on Vudalumab and prostate cancer. You can refer to our press release for more information about the last quarter and full year. We focused our pipeline and discovery work on our T cell engagers because of growing validation for their potential and solid tumors. Supporting this is the continued advance of Vudelumab and prostate cancer, which we'll provide an update on today, and the start of a trial in frontline lung cancer for Vudelumab. And we've decided to reduce our investment in our cytokine drug candidates as part of this focus. Our partnerships and licenses played a significant role for us last year, first with validating data for our XMAB 2 plus 1 CD3 platform from our partner Amgen with their xaleridomic data in prostate cancer, and two Phase 1 programs started in our CD28 bi-specific collaboration with J&J. Additionally, we significantly strengthened our balance sheet with a partial monetization of our Ultramirrors and Moduvi Royals. As a result of that and robust Mile Center royalty revenues, we ended 2023 with $697 million and expect runway into 2027.
We focused our pipeline and discovery work on our T cell engages pet scan because of growing validation for their potential in solid tumors. Supporting this is the continued advance with the Taliban in prostate cancer, where I'll provide an update today and the startup of traveling frontline lung cancer for image, Alabama, and we've decided to reduce our investment in our cytokine drug candidates.
Part of this focusing.
Our partnership some license has played a significant role for US last year first with validating data for our X fab two plus one C. D. Three platform from our partner Amgen with their salary to make data in prostate cancer.
And two phase one program started in our CD 28 by specific collaboration with J&J.
And we significantly strengthened our balance sheet with a partial monetization of our ultimate moggy royalties as a result of that and robust milestone or royalty revenues. We ended 2023 was $697 million and expect runway into 2027.
Bassil I. Dahiyat: And now on to our pipeline. The focus of our clinical pipeline is bispecific T-cell engagers for solid tumors, an area with rapidly growing promise. Solid tumors have been challenging for antibody and cell therapies, but recent data, some of which we'll review momentarily, suggest that CD3 and CD28 bispecifics could play a role as therapies in a range of solid tumors. Key programs for us addressing this opportunity are XMAB 819, an ENTP3 by CD3 XMAB bispecific for renal cell carcinoma, and XMAB 808, a B7H Both are advancing in DOS escalation in Phase 1, and right behind them is XMAP 5.4.1, a Cloudin 6 by CD3 BISPECIFIC that we expect to start in Phase 1 the first half of this year.
Now onto our pipeline.
The focus of our clinical pipeline as bi specific T cell engagements for solid tumors, an area with rapidly growing promise solid tumors have been challenging for antibody in cell therapy, but recent data some of which will review momentarily suggests the CD three and CD 28 by specifics could play a role as therapies in a range of solid tumors.
Key programs for us addressing this opportunity our extra beat one nine and Ian P. P. Three by CD three X mapped by specific for renal cell carcinoma, and extra eight away a piece of an H three by CD 28, <unk> by specific in prostate and other cancers. Both are advancing a dose escalation phase one right behind them is X amount 541 cloud.
Six by CD three by specific do we expect to start phase one the first half of this year.
Cause with Allomap, we initiated a new study its first frontline study in non small cell lung cancer based both of our phase one data in lung cancer and external data suggests the potential advantages they got still checkpoint therapy in this setting.
Bassil I. Dahiyat: For Vudalumab, we initiated a new study, its first frontline study, in non-small cell lung cancer based both on our Phase I data in lung cancer and external data suggesting potential advantages against standard checkpoint therapy in this setting. And we've made progress with our metastatic castrase-resistant prostate cancer studies, both in combination with chemo and monotherapy. And with encouraging monotherapy data, which we'll present in a moment. Finally, we're wrapping up our phase one work next quarter for both XMAPS 564 and 662, taking the PK, PG, and safety data in hand to establish initial product profiles and monitoring the field for further validation of these cytokines before we do any additional development. Underpinning our T cell engages our XMAB bi-specific technology.
We've made progress with our cash metastatic castration resistant prostate cancer studies, both in combination with chemo and monotherapy and work with encouraging monotherapy data were going to present in a moment.
Finally, we're wrapping up our phase one work next quarter for both X amount is 564 and 662.
The PK PD and safety data in hand to establish initial product profiles and monitoring of field for further validation of these cytokines before we do any additional development work.
Underpinning our T cell engages our ex mapped by specific technology. It lets us address the solid tumor opportunity by engineering, our antibodies with a format and affinities designed to give tumor selectivity in the context of each tumor targets particular expression levels and tissue distributions.
Solid tumor targets in particular need a customized approach because they're distributed more broadly the heme tumor targets, which have already been successfully addressed by CD three bi specifics in lymphoma and myeloma.
Our plug and play antibody modules, let us do this work rapidly and as a result, we've got a growing pipeline of molecules with our two plus one design, which is particularly helpful with selectivity for solid tumors.
Bassil I. Dahiyat: It lets us address the solid tumor opportunity by engineering our antibodies with a format and affinities designed to give tumor selectivity in the context of each tumor target, particular expression levels, and tissue distribution. Solid tumor targets in particular need a customized approach because they're distributed more broadly than heme tumor targets, which have already been successfully addressed by CD3 bispecifics in lymphoma and myeloma. Our plug-and-play antibody modules let us do this work rapidly, and as a result, we've got a growing pipeline of molecules with our 2-plus-1 design, which is particularly helpful with selectivity for solid tumors. And here is the first clinical proof of concept for our XMAP 2 plus 1 CD3 format, xaliridamine, which targets STEEP1. Our partner Amgen presented very promising efficacy and tolerability data at ASIMO last October in late-line prostate cancer, usually considered a cold tumor for immunotherapy. This target was challenging due to the limited accessible binding regions outside the cell membrane and non-tumor expression, so we're very encouraged to see this early data for the molecule in a 2 plus 1 format.
Okay.
And here is the first clinical proof of concept for our X map T plus one CD three format is calibrated make which targets steep one.
Our partner Amgen presented very promising efficacy and Tolerability data at ESMO last October in late line prostate cancer, usually considered a cold tumor for immunotherapy. This target was challenging due to the limited accessible binding reaches outside the cell membrane.
And tumor non tumor expression. So we're very encouraged to see this early data for the molecule in a two plus one format.
Amgen has announced they are nearing completion of the phase one study and are planning additional studies in earlier lines of therapy. So we'll be eagerly awaiting their upticks.
Now our own lead X map to plus one CD three by specific as X map 819 targeting E. N. P. P. Three in renal cell carcinoma, we chose E&P P. Threes are targeted because it has exactly the kind of expression profile, we want for a CD three solid tumor targets.
Higher expression on tumor the normal tissues, and nearly uniformly high expression on clear cell renal cell carcinoma, plus it has potential for use in select patients in a range of other tumors.
Bassil I. Dahiyat: Amgen has announced they are nearing completion of the Phase 1 study and are planning additional studies in earlier lines of therapy, so we'll be eagerly awaiting their updates. Now, our own lead XMAB 2 plus 1 CD3 bispecific is XMAB 819, targeting ENPP3 in renal cell carcinoma. We chose ENPP3 as a target because it has exactly the kind of expression profile we want for a CD3 solid tumor target: much higher expression in tumor than normal tissues and nearly uniformly high expression on clear cell renal cell carcinoma.
Also we think renal cell carcinoma has a need for new mechanisms beyond checkpoint inhibitors in teekay eyes and are directly cytotoxic antibody could be well positioned.
Eight one lines design gives us selectivity, we wanted in vitro and we're continuing to advance in dose escalation with both IV and subcutaneous dosing and expect to make significant progress this year towards target dose levels.
I'll shift now to X fab eight await our new T cell engaging mechanism CD 28 targeting this the goal here is to activate T cells via the signal two pathway, which powerfully amplifiers and sustained T cell responses.
We designed data, which by specific format and affinities to try to drive this activation of tumor specific way by requiring sufficient binding to its tumor antigen b 783 to turn on CD 28 signaling a.
Bassil I. Dahiyat: Plus, it has potential for use in select patients and a range of other tumors. Also, we think renal cell carcinoma has a need for new mechanisms beyond checkpoint inhibitors and TKIs, and a directly cytotoxic antibody could be well-positioned. 819's design gives us the selectivity we wanted in vitro, and we're continuing to advance in dose escalation with both IV and subcutaneous dosing and expect to make significant progress this year toward target dose levels. Now, I'll shift now to XMAB 808, our new T cell engager mechanism and CD28 target. The goal here is to activate T-cells via the SIGNL2 pathway, which powerfully amplifies and sustains T-cell responses. We designed 808's biospecific format and affinities to try to drive this activation in a tumor-specific way by requiring sufficient binding to its tumor antigen, B7H3, to turn on CD28 signaling.
A key part of our approach is a lower potency CD 28 binding domain that we think could give us control of CD 28 signaling and improved tolerability.
We picked <unk> 783, because it offers high expression across a range of tumor types, creating an opportunity to potentially treat multiple cancers in combination with either checkpoint inhibitors, where CD three bi specifics.
CD 28 targeting has generated a lot of interest among clinicians and across the industry in the current phase one study in combination with Campbellism Nab is progressing well and escalation.
Now our latest CD three by specific is set to enter the clinic Imminently X men 541 targets cloud and six which is highly expressed on the majority of the variant cancers and also on several other tumor types.
It's very promising expression profile. It is a selectivity design challenge because there are multiple closely homologous clouds.
We think we addressed it with careful bindings main engineering and our two plus one format.
Bassil I. Dahiyat: A key part of our approach is a lower potency CD28 binding domain that we think could give us control of CD28 signaling and improve tolerability. We picked B7H3 because it offers high expression across a range of tumor types, creating an opportunity to potentially treat multiple cancers in combination with either checkpoint inhibitors or CD3 bispecifics. CD28 targeting has generated a lot of interest among clinicians and across the industry, and the current Phase I study in combination with Pembrolizumab is progressing well in escalation. Now, our latest CD3 bi-specific is set to enter the clinic imminently. XMEP541 targets Cloudin 6, which is highly expressed in the majority of ovarian cancers and also in several other tumor types.
It's about 540 <unk> is opening and we expect to be in patients. The first half of this year, we're planning to apply lessons learned for solid tumor CD three dosing from both internal and external programs to move the study quickly.
Now I'm going to turn it over to Nancy for the <unk> update.
Thanks, Praful I'm excited about the encouraging new data, we have just share from the prostate cancer monotherapy cohort.
We could go to the next slide this cohort as part of the overall everyday on that program, which consists of four studies based on the outcome of the phase. One study we moved into two tumor specific expansions. Initially this study 71 704 in metastatic castrate resistant prostate cancer in combination.
Asian with standard of care chemo and other agents and studies 71705 that included patients with gynecologic malignancies, and a monotherapy in metastatic castrate resistant prostate cancer cohort, which I'm going to further describe.
Bassil I. Dahiyat: Though it has a very promising expression profile, it is a selectivity design challenge because there are multiple, closely homologous clouds. We think we have addressed it with careful Bindings Main Engineering and our 2 plus 1 format. XMAT 541's ID is open, and we expect to be inpatients the first half of this year. We're planning to apply lessons learned for solid tumor CD3 dosing from both internal and external programs to move the study quickly. Now I'm going to turn it over to Nancy for the Vidal map update.
The next slide.
Rusty monotherapy cohort.
Required patients ever resist miserable disease, including visceral sites or lymph nodes and the patients had to have progressed. After all other appropriate therapy for the element I was given every three weeks based as a flat dose based on our PK analysis of earlier studies.
Nancy Valenti: Thanks, Bassil. I'm excited about the encouraging new data we have to share from the prostate cancer monotherapy cohort. If we could go to the next slide, please.
You can see that this study enrolled a heavily pretreated patient population that is had exhausted available standard of care therapies with a median of four.
Nancy Valenti: This cohort is part of the overall VUDELEMED program, which consists of four studies. Based on the outcome of the phase one study, we moved into two tumor-specific expansions initially. The study 7.1704 in metastatic castrate-resistant prostate cancer in combination with standard-of-care chemo and other agents and study 7.1705 that included patients with gynecologic malignancies and a monotherapy metastatic castrate-resistant prostate cancer cohort, which I'm going to further describe.
Her prior therapies 100 per cent received prior anti androgen therapy, although one received prior chemotherapy and 86% where econ one performance status.
As noticed as noted the study protocol required patients with measurable disease at baseline, which is why we see a high rate of visceral metastases and high median baseline Psa.
Reduction in target lesions and disease control are encouraging for such a heavily pretreated patient population as you can see on the right with a resist response rate of 35% and a disease control rate of 50% and the Spider plot shows we have several lasting responses.
Nancy Valenti: The prostate monotherapy cohort required patients to have resistant measurable disease, including visceral sites or lymph nodes, and the patients had to have progressed after all other appropriate therapy. Vudelumab was given every three weeks as a flat dose based on our PK analysis of earlier studies. You can see that this study enrolled a heavily pretreated patient population that had exhausted available standard of care therapies, with a median of four prior therapies, 100% received prior anti-androgen therapy, all but one received prior chemotherapy, and 86% were ECOG1 performance status. As noted, the study protocol required patients with measurable disease at baseline, which is why we see a high rate of visceral metastases and high median baseline PSAs. Rejection in target lesions and disease control are encouraging for such a heavily pre-treated patient population, as you can see on the right. A response rate of 35% and a disease control rate of 50%.
One patient with stable disease past 48 weeks.
Yeah.
Deep PSA reduction was also seen in three patients, giving a PSA 90 rate of 25% and a fourth patient with a nearly a 50% payout.
Say, who is still on study to describe when especially poor prognostic patient who responded well to run Allomap. This patient had three liver Mets and total disease burden of 12 centimeters and appears say at baseline of 180 nanograms per 1000 and achieved a confirmed PR a P. S.
Say 90 and was in response forever 22 weeks.
The treatment emergent adverse events highlight the Tolerability has been generally well managed by dose modifications with only two treatment discontinuation. Unfortunately, there has been one case of grade five immune related.
Nancy Valenti: And the spider plot shows we have several lasting responses and one patient with stable disease past 48 weeks. Deep PSA reduction was also seen in three patients, giving a PSA 90 rate of 25% and a fourth patient with nearly a 50% PSA who is still on study. To describe one especially poor prognostic patient who responded well to Vanillimab; this patient had three liver meds, a total disease burden of 12 centimeters, and a PSA at baseline of 180 nanograms per mil and achieved a confirmed PR, a PSA 90, and was in response for over 22 weeks. Treatment immersion adverse events highlight that tolerability has been generally well managed by dose modifications with only two treatment discontinuations Unfortunately, there has been one case of grade five immune-related mediated hepatitis.
[noise] mediated hepatitis patient's treatment course was complex and this is the only known grade five immune mediated hepatitis event and over 240 patients that we've treated with readout will map to date.
Reviewing.
Specific immune related adverse events generally the events are what would.
What we would expect with checkpoint inhibitor therapy the rate of grade three events that you can see on the right are generally limited and specific to several patients. Overall, we are encouraged by the Tolerability profile of the Q3 weeks flat dosing schedule with Fidel map.
In summary, we have observed encouraging single agent activity in heavily pretreated patient population. This is consistent with the data from the phase one study in prostate cancer, where we had patients with six and 10 months duration of response.
Nancy Valenti: The patient's treatment course was complex, and this is the only known grade five immune-mediated hepatitis event in over 240 patients that we've treated with Ritalamab to date, reviewing specific immune-related adverse events. Generally, the events are what we'd expect with checkpoint inhibitor therapy. The rate of grade three events, which you can see on the right, was generally limited and specific to several patients. Overall, we are encouraged by the tolerability profile of the Q3 week flat dosing schedule with FidelMap. In summary, we have observed encouraging single agent activity in a heavily pre-treated patient population. This is consistent with the data from the phase one study in prostate cancer, where we had patients with six and ten months of duration of response. The Delmib safety profile is consistent with other checkpoint inhibitors, and we observed limited treatment discontinuations. Now I will turn this over to Dane to share comparative data to place these results in context. Thanks, Nancy.
Safety profile is consistent with other checkpoint inhibitors, and we observed limited treatment discontinuation.
Now I will turn this over to Dave to share comparative data to place these results in context.
Thanks, Nancy as.
As you can see on the next slide these emerging data.
Support us enrolling more patients into the monotherapy cohort when you put the data into the context of the broader novel therapeutic landscape under development. It really is clear why we and our investigators during our discussion I ask could you were so encouraged about continuing to study when you compare the baseline characteristics of <unk>.
Patients versus our peer studies <unk> monotherapy cohort is among the most heavily pretreated and has the most advanced disease upon enrollment as shown by nearly all having he coughlin and all having measurable disease comparatively only theres algorithmic dose escalation study has enrolled similar patients that are very late line and poor performance status.
Dane Leone: As you can see on the next slide, these emerging data support us enrolling more patients into the monotherapy cohort. When you put the data into the context of the broader novel therapeutic landscape under development, it really is clear why we and our investigators during our discussion at ASCO-GU were so encouraged about continuing to study. When you compare the baseline characteristics of our patients versus our peer studies, the Vidal-Mapp monotherapy cohort is among the most heavily pretreated and has the most advanced disease upon enrollment, as shown by nearly all having ECOG1 and all having measurable disease. Comparatively, only the xaliridamide dose escalation study has enrolled similar patients that are very late in line and have poor performance status.
Yes.
Despite the remarkably advanced patient population patients treated with a doubt map how comparable resist response rate versus the peer studies in this table and experienced deep PSA 90 responses.
Importantly, we think that resist response and deep PSA response are required for translating into effective durability of response and ultimately survival outcomes for these patients.
Regarding tolerability using the Q3 week flat dose schedule of Odell Mab that support a manageable safety profile compared to our peers.
Overall, considering the early nature of the Dow <unk> monotherapy cohort, we are encouraged by the clinical benefit for these advanced prostate cancer patients that have been treated well beyond current standard of care and we look forward to evaluating a larger cohort of patients by year end.
Dane Leone: Despite the remarkably advanced patient population, patients treated with Adalimab have comparable resistance response rates versus the peer studies in this table and experienced DPSA-90 responses. Importantly, we think that resistance response and deep PSA response are required for translating into effective durability of response and ultimately survival outcomes for these patients. Regarding tolerability, using the Q3 week flat dose schedule of Udalmab has supported a manageable safety profile compared to our peers.
Now on the next slide beyond prostate cancer, we are executing on the start of our frontline non small cell lung cancer study of <unk> plus chemotherapy and we are excited that this study is underway with the first patient dose in the fourth quarter of last year and with that I'll turn back to Basel four view of our corporate goals for 2024.
Thanks, Dan Here's a look at our priorities for 2024, we're starting with a strong balance sheet. As you can see we're looking forward to this year really bringing focus to our solid tumor by specifics pipeline, where we have a lot going on for our CD three and CD 20, a T cell engages and for <unk> of course, we're doing discovery work on additional CD three in <unk>.
Dane Leone: Overall, considering the early nature of the Vidal-Madma therapy cohort, we are encouraged by the clinical benefit for these advanced prostate cancer patients that have been treated well beyond the current standard of care, and we look forward to evaluating a larger cohort of patients by year-end. Now, on the next slide, beyond prostate cancer, we are executing on the start of our frontline non-small cell lung cancer study of Adalimab plus chemotherapy, and we are excited that this study is underway with the first patient dose in the fourth quarter of last year. And with that, I'll turn back to Basil for a review of our corporate goals for 2024. Thanks, Dane. Here's a look at our priorities for 2024. We're starting with a strong balance sheet.
28 by specifics and we'll select our next 90 candidate later this year.
Operator, we'll now open the call to questions.
Yeah.
Thank you.
At this time, we will now conduct the question and answer session.
As a reminder to ask a question you will need to press star one one on your telephone and wait for your name to be announced.
To withdraw your question. Please press star one again, please standby, while we compile the Q&A roster.
Okay.
Our first question comes from Jonathan Chang.
Leerink partners, our Leerink partners the floor is now yours.
Hi, guys. This is Dylan drags on for Jonathan Thanks for taking our questions first of all would you be able to comment on how investors should be thinking about when you might be able to see initial clinical data from the MTV three study.
Sure I'll take that one.
So we're not commenting on data just yet and what we're trying to do is characterized with a sufficient patient number and follow up the outlines of the effective dose level as we pulled together a dosing regime. These are CD three bi specifics. So you want to have that you wanted to have your priming at step up. This is we've made great progress and we really hope that this year.
Bassil I. Dahiyat: And as you can see, we're looking forward to this year, really focusing on our solid tumor biospecifics pipeline, where we have a lot going on for our CD3 and CD28 T cell engagers and for Vudalumab. Of course, we're doing discovery work on additional CD3 and CD28 biospecifics, and we'll select our next IND candidate later this year. The operator will now open the call to questions. Thank you. At this time, we will now conduct the question and answer session. As a reminder, to ask a question, you will need to press star one on your telephone and wait for your name to be announced.
We'll have a lot more knowledge about it and then when we get close to having the decision to disclose we will tell you. So we're not guiding anything there yet.
Great. Thanks, and if I could just sneak in one more you guys set the stage very well with their comparative table there, but looking ahead to the go forward vision for both mono and combination approaches how would you guys set the bar.
Yeah.
Yes, I guess, maybe the mono first I mean yesterday, you guys want to take that what's the bar for advance the comparable.
Operator: To withdraw your question, please press star 1 1 again. Please stand by while we compile the Q&A rocket. Our first question comes from Jonathan Chang, of Lear, Inc. Partners, or Lear, Inc. Partners. The floor is now yours. Hi guys, this is Dylan Drake, sponsor Jonathan.
Yes sure.
Great question, when we when we look at the patients that we've enrolled into the monotherapy cohort while continuing to enroll.
These are patients that are as late line as you can get and have exhausted standard of care therapy available to them.
Unnamed: Thanks for taking our questions. First of all, would you be able to comment on how investors should be thinking about when we might be able to see initial clinical data from the ENPB3 study? Sure, I'll take that one.
As such what we've really decided to do and engaging the signal that we'll have as we hopefully get a cohort of 20 to 30 patients enrolled over the course of this year.
Bassil I. Dahiyat: So, we're not commenting on data just yet, and what we're trying to do is characterize, with a sufficient number of patients and follow-up, the sort of outline of the effective dose level as we pull together a dosing regime. These are CD3 bispecifics.
Look at some of the contemporary studies, where cabana tactful has been used as a control arm.
And in those studies, namely the control arm for therapy or they're very recently reported part two of Checkmate 650, you've seen or resist response rate for capacity on that 11% to 24% range and a PSA 50 response rate of 24% to 37%.
Bassil I. Dahiyat: So, you want to have that; you want to have your priming and step-up doses. We've made great progress, and we really hope that this year we'll have a lot more knowledge about it. And then when we get close to having the decision to disclose, we will tell you. So, we're not hiding anything there yet. Great, thanks. If I could just sneak in one more.
This is why we're we're quite encouraged with what we're seeing.
In the cohort now with clinical activity of <unk> monotherapy.
And hopefully with a larger cohort and more follow up we can then try and extrapolate what would be needed.
Unnamed: You guys set the stage pretty well with the comparative table there, but looking ahead to the go-forward decisions for both the mono and combination Zutalan lab approaches, how would you guys set the bar? Yes, I guess maybe the mono first. I mean, Nancy and you guys want to take that?
In terms of survival outcomes in Gabon, the tax law for references generally come out around eight months for radiographic progression free survival.
And right now based on some of the durability. It seems like we're pretty in pretty good shape.
Dane Leone: What's the bar for advanced comparable? Yeah, sure. Great question.
No no.
The combo cohort I guess, we've got.
Different baselines, there to look up yes.
Dane Leone: When we look at the patients that we've enrolled into the monotherapy cohort and will continue to enroll, these are patients that are as late in line as you can get and have exhausted every standard of care therapy available to them. As such, what we've really decided to do in engaging the signal that we'll have as we hopefully get a cohort of 20 to 30 patients enrolled over the course of this year is look at some of the contemporary studies where cabazitaxel has been used as a control arm. And in those studies, namely the control arm for therapy or the recently reported Part 2 of Checkmate 650, you've seen a resistance response rate for cabazitaxel in that 11 to 24 percent range and a PSA 50 response rate of 24 to 37 percent.
And in the Carbone combination cohort with Docetaxel.
You really have to think about what docetaxel might be able to do.
And what would be post androgen receptor inhibitor.
Exposure for these patients and again the landscape will continue to change before Victor but.
Historically, if you're if you're looking at the tax 327 study.
You'd be looking at PSA 50 response range of 40% to 50%.
And a fairly low resist response rate of somewhere around 10%.
That said the survival curves are a bit.
Better for that that line in that setting with Docetaxel monotherapy.
But that's kind of what you have to think about when youre doing a combination.
Dane Leone: This is why we're quite encouraged with what we're seeing in the cohort now with clinical activity of Edelman monotherapy. And hopefully, with a larger cohort and more follow-up, we can then try and extrapolate what would be needed in terms of survival outcomes. And Kabazitaxel, for reference, generally comes out around eight months for radiographic progression-free survival. And right now, based on some of the durability, it seems like we're in pretty good shape.
<unk> with Docetaxel at this point.
Perfect. Thanks, so much I appreciate it.
Thank you one moment please.
Okay.
Our next question comes from the line of Exar Doral from BMO capital markets.
Great. Thanks for taking my question I guess, maybe on the on the.
The safety profile.
Bill or Matt.
Eddie.
Anything you can or will incorporate into the study to maybe economy to mitigate.
The autoimmune hepatitis is this something that is just unique to this patient or.
Dane Leone: Now then, for the combo cohort, I guess we've got different baselines there to look at. Yeah, in the combo combination cohort with DoseTaxel, you really have to think about what DoseTaxel might be able to do in, you know, what would be post-angiogen receptor inhibitor exposure for these patients. And again, the landscape will continue to change with Plovicto, but historically, if you're looking at the TAX-327 study, you'd be looking at a PSA-50 response range of 40 to 50 percent and a fairly low resistance response rate of somewhere around 10 percent. That said, the survival curves are a bit better for that line and that setting with dose-to-taxyl monotherapy, but that's kind of what Perfect. Thanks so much.
There are other things sort of going on that you need to understand and then also ex now 564, just wondered the decision to sort of pause that was that data driven or whatever other contributing factors. If you could comment on that.
Two two points.
Thank you.
Sure. So I'll I'll I'll talk of them gone through the extra 564, then maybe Nancy can take the question on the <unk> safety profile. So for 564, it was really driven by our as much as anything by our decision to focus on our T cell engages our resources, our capital and our people.
And looking at how the class a side.
Cytokines are generally an IL two T Reg driving cytokines in particular has evolved there is still I think a lot of the.
Unnamed: I appreciate it. Thank you. One moment, please.
Outstanding data coming in the next year from other companies about about.
Etzer Darout: Our next question comes from the line of Etzer Darout from BMO Capital Markets. Okay. Thanks for taking the question. I guess maybe on the safety profile of the LMAB, if there's anything you can or will incorporate into the study to maybe kind of mitigate this autoimmune hepatitis? Is this something that is just unique to this patient? Or are there other things sort of going on that you need to understand? And then also, on XMAB 564, I just wondered what the decisions were to sort of pause that.
Efficacy about how much potential does this class have and with our study having progressed and given us a reasonable look at our PK PD and safety, we think that that's the time to to conserve resources and wait and see how the field evolves well positioned we're well positioned to ramp up again, but it's about.
Focus now and for 2024 pipeline focus is the key for us encore.
So it was really more just strategy driven with that maybe Nancy do you want to touch on the question on <unk> Yeah.
Bassil I. Dahiyat: Was that data-driven or, you know, whatever other contributing factors, if you could comment on that, to stop that study? Thank you. Sure.
So I'll go back to the patient with the hepatitis Ted.
Bassil I. Dahiyat: So, I'll talk, I'll go through XMAP564, and then maybe Nancy can take the question on the VidalMap safety profile. So, for 564, it was really driven by our, as much as anything, by our decision to focus on our T cell engagements, our resources, our capital, and our people. And, you know, looking at how the class cytokines generally, and IL-2 Treg driving cytokines in particular, have evolved, there's still, I think, a lot of outstanding data coming in the next year from other companies about efficacy, about how much potential this class has. And with our study having progressed and given us a reasonable look at our PKPD and safety, we think that that's the time to Well-positioned, We're well-positioned to ramp up again, but it's about focus now, and for 2024, pipeline focus is the key for Xencor. So it was really more just strategy-driven.
And that's the only immune related hepatitis Delta we've seen across.
Our program with more than 240 patients treated both in the monotherapy and combination settings.
The patient had responded to therapy, but did have other treatment emergent adverse events.
Before that including diabetes mellitus in diabetes, and diabetic ketoacidosis thyroiditis hyperkalemia light pace increase.
So a bit of a complex course here.
We have looked across the entire program.
And we don't see anything concerning relating hepatitis.
As far as the.
The protocol of the investigators we have emphasized to the investigators to be watchful for this and communicated with them. The protocol does include the NCC and guidelines for treatment and it's also consistent with.
<unk> guidelines and other society guidelines like the gastric.
Gee I'd guidelines for a monetary and treatment and so we do include screening and baseline for any diseases that might contribute to hepatitis and we have frequent laboratory monitoring.
Bassil I. Dahiyat: With that, maybe Nancy, if you want to touch on the question about Voodalabat? Yeah, so I'll go back to the patient with the hepatitis death. And that's the only immune-related hepatitis death we've seen.
Yeah.
Great. Thank you for the color.
Sure. Thanks, Patrick.
Thank you for the question one moment please.
Okay.
Our next question.
Nancy Valenti: Our program with more than 240 patients treated, both in the monotherapy and combination setting. The patient had responded to therapy but did have other treatment emergent adverse events before that, including diabetes mellitus and diabetes, diabetic ketoacidosis, thyroiditis, hyperkalemia, lipase increase, so a bit of a complex course here. We have looked across the entire program, and we don't see anything concerning relating to hepatitis. As far as the protocol and the investigators, we have stressed to the investigators to be watchful for this and communicate it with them. The protocol does include the NCCN guidelines for treatment, and it's also consistent with ASCO guidelines and other society guidelines, like the gastric GI guidelines for monitoring and treatment. And so we do include screening at baseline for any diseases that might contribute to hepatitis, and we have frequent laboratory monitoring. Great. Thank you for the color.
Comes from Gregory <unk> of RBC capital markets the floor is yours.
Hi, Thank you so much for taking our questions. This is the portfolio Greg.
Just to confirm.
If this monotherapy data with from a particular well.
The subtypes.
What's how does the trial used to be characterized and if I may secondary really from that date.
Data comparison table I think the PSA 90 looks competitive, but PSA 50 looked a little lower just curious if you have any hypothesis on why why the data it looks that way. Thank you.
I'll touch on the specifics of the trial in the population. So I think just to be careful there's two studies ongoing that will work, we're starting prostate cancer with <unk>. The monotherapy study. The one we discussed today is not subdivided by molecular subtype, which people with clinically defined high risk disease, which includes extra pelvic and <unk>.
Metastasis. So that's a population that's independent of molecular subtype in that regard the other study our combination with chemo study.
Etzer Darout: Thanks, Cedric. Thank you for the question. One moment. Our next question comes from Gregory Rinza of RBC Capital Markets. The floor is yours.
That study is subdivided by molecular subtype that has a different study we didn't discuss data for that Wednesday, we're enrolling still accrued patients and more follow up and we hope to have a lot more clarity later in the year on that program.
Operator: Hi, thank you so much for taking our questions and giving us such support folks. Um, just to confirm... This monotherapy data was from a particular molecular subtype, and that was how the trial was conducted.
And also I guess first half of next year really bring it all together.
Dane Leone: The PSA-90 looks competitive, but the PSA-50 looks a little lower. I'm just curious if you have any hypothesis on why the data looks lower. So, I'll touch on the specifics of the trial and the population. So, I think just to be careful, there are two ongoing studies now where we're studying prostate cancer with Vudalumab. The monotherapy study we discussed today is not subdivided by molecular subtype. It's people with clinically defined high-risk disease, which includes extra-pelvic and visceral metastases. So, that's a population that's independent of molecular subtype in that regard.
So that just I just want to make sure that this is this is not from the molecular subtype dividing study.
On the comparison table, Dan you want to answer that one on the PSS, Yes sure. That's a great question that we looked at quite extensively once we had this data cut and were able to review the data with our investigators starting <unk>.
Well it seems to be as is somewhat of an artifact of taking.
Taking patients that are required to have measurable disease at baseline.
Versus other studies that also include bone only.
Dane Leone: The other study, our combination with chemo study, that study is subdivided by molecular subtype. That's a different study. We didn't discuss data for that one today. We're still enrolling a crew of patients and more follow-up, and we hope to have a lot more clarity later in the year on that program and also, I guess, the first half of next year, really bring it all together. So, I just want to make sure that this is not from a molecular subtype dividing study.
And as you can see on that table most of our peer studies outside maybe one with a similar mechanism of action.
Is more of a mixed patient population and what we see in those studies as you will get more PSA fifties that don't necessarily correlate to a resist response some of those patients do not have measurable disease at baseline.
And our cohort to really get a clinical benefit those patients will need either a resist response or PSA 90. So.
Dane Leone: On the comparison table, Dan, do you want to answer that one about the PSAs? Yeah, sure. That's a great question that we looked at quite extensively once we had this data cut and were able to review the data with our investigators during ASCO-GEU. What it seems to be is somewhat of an artifact of taking patients that are a part of that measurable disease, that baseline, versus other studies that also include bone-only. And as you can see on that table, most of our peer studies outside maybe one with a similar mechanism In our cohort, to really get clinical benefit, those patients will need either a resistive response or a PSA-90, so I think there are two things there. One, is PSA-50 for patients that are this advanced in their disease course relevant for survival outcomes? Very debatable, but what is definitely needed are those resist responses and PSA-90s.
I think theres two things there one is PSA 50 for patients that are this advanced in their disease course are relevant for survival outcomes very debatable.
But what is definitely needed as those resist responses and PSA nineties.
Yes.
Q.
Thank you one moment for our next question.
Our next question comes from the line of co firing pollen on P. T. I G. The floor is yours.
Yeah. Good evening, Thanks for taking my questions. My question is on <unk>.
No.
First on the safety profile can you tell us how the safety profile looks in comparison with it being evil combination and how you are thinking about the dose that we'll use.
Going forward.
My second question is also for the no go no go decision how many patients you plan to enroll in monotherapy and combination cohorts for that and it gives me. The only factor you are considering to make these decisions and the last one is also from the same trial.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Kovari Polman from BTIG. The floor is yours.
Kovari Polman: Yeah, good evening. Thanks for taking my questions. My questions are mostly about Vidal and Mab.
Any color you can provide on how many patients had bone disease and were there any responses observed in those patients. Thank you.
Kovari Polman: So first of all, can you tell us how the safety profile looks in comparison with the epinephril combination and how you are thinking about the dose that will be used going forward? And my second question is also about the no-go, no-go decision. How many patients do you plan to enroll in monotherapy and combination cohorts for that? And is efficacy the only factor you're considering to make these decisions? And the last one is also from the same trial.
Hey, thanks, great. So that's a set of questions I think maybe the one that's more just generically descriptive as your first one.
<unk> safety versus it being Evo, which is a broad kind of amorphous question, but will take a crack at it and what our dose going forward as Nancy do you want to jump in on that one yeah. I mean overall, what we've seen so far is the safety profile looks similar.
Kovari Polman: Any color you can provide on how many patients had bone disease and whether there were any responses observed in those patients? Thank you. Hey, thanks, Kaveri. So that's a set of questions. I think maybe the one that's more just generically descriptive is your first one.
Two other checkpoint inhibitors. So we haven't seen anything that says that this is different.
Markedly different in some.
Wei.
In some way that wouldn't be unfavorable to the product.
Yes.
Bassil I. Dahiyat: Vidalmeb safety versus ipineva, which is a broad kind of amorphous question. But, you know, we'll take a crack at it and see what our dose going forward is. Nancy, do you want to jump in on that one?
But I guess I can say that overall I mean, there's a lot of data out there on it.
A single monotherapy checkpoint inhibitors as well as combinations.
So broadly similar to that.
Nancy Valenti: Yeah, I mean, overall, what we've seen so far is the safety profile. It looks similar to other checkpoint inhibitors. So we haven't seen anything that says that this is different, markedly different in some way that wouldn't be unfavorable to the product. But I guess I could say that overall. I mean, there's a lot of data out there on IPIs, single monotherapy checkpoint inhibitors, as well as combinations. So broadly, we're similar to that.
Do you want to yeah and on the dose going forward note that in our lung cancer study. The newest study we started as well as in the mono therapy prostate study, which was which was the second newest we have switched to a Q3 week schedule using flat doses and I think that's given us.
Have a good feeling that the Q3 week might have some benefits over the Q2 week.
Weight based dosing with regard to it being evo, even though we've got over 240 patients now it's still hard to parse out those subtle differences, we don't see the kind of colitis that often bedeviled the hippie therapy at high doses of note, we're giving much higher doses of our drug than the current sort of at the regime of one milligram per kilogram.
Nancy Valenti: Yeah, and on the dose going forward, note that in our lung cancer study, the newest study we started, as well as in the monotherapy prostate study, which was the second newest, we have switched to a Q3 week schedule using flat doses, and I think that's given us, you know, a good feeling that the Q3 week might have some benefits over the Q2 week weight-based dosing. You know, with regard to ipinevo, even though we've got over 240 patients now, it's still hard to parse out those subtle differences. We don't see the kind of colitis that often bedevils ipi therapy at high doses and note we're giving much higher doses of our drug than the current sort of ipi regime of 1 milligram per kilogram.
So I think that's maybe the best we can say comparatively.
Ross such a range of Ah.
Studies and whatnot, but generally very checkpoint like and then on your second question go No go a number of patients that we would hope to have for both the common when the motto. So by first half next year. We're looking at on the order of I guess roughly 30 patients in each of those settings the keys.
Bassil I. Dahiyat: You know, so I think that's maybe the best we can say comparatively across such a range of studies and whatnot, but generally very checkpoint-like. And then on your second question, the number of patients that we'd hope to have for both the combo and the mono, you know, so by the first half next year, we're looking at on the order of, I guess, roughly 30 patients in each of those settings. The chemo study, in particular, in the main cohort, which is our no-targetable mutations cohort, which is our now-dosotaxel combo, and then in our monotherapy study as well. So in that, you know, we're aiming for 20 patients; hopefully, we'll get pretty close to that and be able to make decisions.
Most study in particular in the the main cohort, which is R. No target all mutations cohort, which is R. Now Docetaxel combo and then our monotherapy study as well so in that.
We're aiming for 20 patients, who will get pretty close to that and be able to make decisions.
It was that was your.
I think it would be helpful. Maybe Nancy you could just explain the.
The difference between measurable disease, and non measurable disease at baseline because I think that that might be.
Helpful for everyone.
Sure I mean measurable disease me.
Yes.
Very basically two dimensions and it's got to be in a metastatic site and in Oregon or measurable Linda no bigger than a normal lymph node.
Bassil I. Dahiyat: I think it would be helpful, maybe Nancy, if you could just explain the difference between measurable disease and non-measurable disease at baseline because I think that might be helpful for everyone. I mean, measurable disease means it has basically two dimensions, and it's got to be a metastatic site in an organ or a measurable lymph node bigger than a normal lymph node. Non-measurable would typically be bone-only disease, or if a patient had bone-only disease.
Non measurable.
Would typically be bone disease.
Disease.
Or if a patient had only disease or patients head.
Measurable disease and they could've also had bone disease on top of that.
I can tell you two of the four responders had bone disease. In addition to their other measurable disease. So we have seen responses in bony in patients who had bone disease.
Nancy Valenti: Our patients had measurable disease, and they could have also had bone disease on top of that. I can tell you that two of the four responders had bone disease in addition to their other measurable disease. So we have seen responses in patients who have bone disease.
Got it yeah, that's what I wanted to know thank you. Thanks for the color.
Kovari Polman: Yeah, that's what I wanted to know. Thank you. Thank you for that question. One moment, please. Our next question comes from the line of Brian Chung from J.P. Morgan. The floor is yours.
Thank you for that question one moment please.
Yeah.
Our next question.
Comes from the line of Brian <unk> from J P. Morgan the floor is yours.
Operator: Hey Bassil, hey guys. Thanks for taking my questions today. Maybe the first one is, you know, just on the three confirmed responders, I think just kind of piggybacking on what was the question prior to this. What was the background of the three confirmed responders? Can you just kind of give us, you know, how many lines they have? And, you know, kind of give us a sense of, you know, what their historical responses were to prior AR, or even I see that they had, you know, some patients who had radiation. So just curious, like, what were their responses like? And I have a follow-up question. Yeah, I mean, Nancy, you could take that, you know, all the details. I'd say they were really, really heavily pre-treated and in rough shape when we got them.
Oh, Hey, guys. Thanks for taking my questions today.
Maybe a first one is.
It was just under three confirmed responders I think just kind of piggybacking on what.
What was the question prior to this.
What was the background on the three confirmed responders can you just kind of give us what how many lines that you have.
And you know kind of give us a sense of what their historical response, thus far.
Pi or or even.
See that they they had some patients happier.
So I'm just curious like what where their response was like and I have a follow up thank you.
Yeah, Yeah, I mean, Nancy you could take that you know all the details, let's say they were really really heavily pretreated.
In rough shape, when we got him.
Nancy Valenti: Yeah, they had to be progressing through prior therapies. They had to have, you know, at least two prior therapies. You know, I'm looking at the background, and they had anywhere from three to like seven prior therapies, including XLT. Yeah, that's a lot of detail, Brian, so we're picking up our notes. So, you know, one patient had three prior therapies, not including any radiation. The second patient had three prior therapies. The third patient had six prior therapies, not included. So none of these are with radiation or counting that. And the last patient had two prior therapies. They all included one.
They have to be progressing through prior therapies.
I had to have.
You know at least two prior therapies.
You know there you know I'm looking at the background.
And you know they have anywhere from three to like seven prior therapies.
Including.
Ex certainty.
I mean I'm just looking at yes, that's a lot of detail Brian. So you can never notes yeah.
So you know one patient had three prior therapies not including any radiation second patient has.
Three prior therapies, the third patient had.
Six prior therapies not included so none of these are with radiation or counting that and the last patient in two prior therapies.
They all included.
Nancy Valenti: They all included docetaxel and or one included carboplatin, to Head Pryor Radio Therapy. Let me just see. That's, I can't really comment on their prior responses, but maybe in an upcoming presentation we could drill down into each individual patient. Yeah, yeah, but suffice to say they've seen a lot of prior therapy, Brent. Okay, and then a follow-up here is, you know, as you're looking at this data, and I think the last time we saw the combo data, maybe back in, let's see, I think back in 2022, how should we think about the low-hanging fruit piece? You know, what is the lowest-hanging subset of the MCRPC patient that, you know, the investor should think of when it comes to a dial You know, and is it high-risk? Is it genetically defined?
Hi.
They all included Docetaxel and or one one included Carboplatin.
<unk>.
Two had prior radiotherapy.
Let me just see.
That's I can't really say that.
On their prior responses, but maybe in an upcoming presentation, we could drill down into each individual patient, yes, yes, but suffice to say they've seen a lot of prior therapy Brent.
Okay, and then a follow up here.
You are looking at this data and.
I think the last time, we saw the combo data maybe back in let's see I think back in 2022.
Should we think about the low hanging fruit piece, you know what what does it lowest lowest hanging subset of <unk> patients that.
Investors should think of when it comes to with Allomap.
And is it high Ras is a genetically defined how do you think about the low hanging fruit.
Dane Leone: How do you think about the low-hanging fruit, you know, either with combo or monotherapy? Yeah, I think it's a great question that we're obviously going to have a fuller answer to as we get these cohorts enrolled over the course of this year and can really look for a reliable signal, hopefully in 30 patients per cohort, for immunotherapy and for the combination. But the way we're thinking about it now is we just had an update on Part 2 of Checkmate 650 at ASCO-GU, where ipineva was tried in every foreseeable combination relative to cabasa daxil. The emergent signal that we have at a small end right now is better than anything that was achieved in that study in a comparable patient population, post-taxane patients. And, you know, so that's step one.
Either with combo arm monotherapy. Thanks.
Yes, I think it's a great question that we're obviously going to have a fuller answer too as we get these cohorts enrolled over the course of this year and can really look for.
A reliable signal.
Hopefully.
30 patients per cohort.
Monotherapy and for the combination.
But the way we're thinking about it now is we just had an update on part two of Checkmate 650 at <unk>.
<unk> was tried in every foreseeable combination relative to capacity taxol. The emergent signal that we have in a small line right now is better than anything that was.
<unk> in that study.
And Ah comparable patient population post taxane.
<unk>.
And.
Dane Leone: We think we have something differentiated that hasn't been done with iotherapy before in this heavily pretreated patient, even going back to the table that we have looking across all of our peer studies. And then step two is more of a question, I think you're asking, of how we see the treatment landscape evolving. As, you know, everyone knows, Plovicto is probably going to be used more and more. They had a good year of commercial uptake in the United States.
So that's step one we think we have something differentiated that hasnt been done with with an Io therapy before in this heavily pretreated patients.
Even going back to the table that we have looking across all of our peer studies.
And then step two is is more of a question I think you are asking of how we see the treatment landscape evolving.
As everyone knows predictor is probably going to be used more and more they had a good 2023 of commercial uptake in the United States and so that has to be on our minds as we look through future development, but the interesting point here is the toxicity profile of the dial mab as non overlapping with predict though.
Dane Leone: And so that has to be on our minds as we look through future development. But the interesting point here is the toxicity profile, the dialed map, is non-overlapping with Plovicto. So that's one.
Dane Leone: And secondly, there's emerging evidence presented and published late last year that treatment Plovicto might actually sensitize the tumor microenvironment to checkpoint target therapy. And, you know, this all has to be proven out in the clinic within larger studies. And step one for us is still defining what we think the clinical profile is of Voodow Mab monotherapy for these heavily treated Mastac patients with measurable disease. But once we understand that, I think there are a number of options for moving forward in an intelligent manner in the development of this drug. So, we're excited about what we're seeing. Again, it's early days here, so we don't want to, you know, get over our skis, but we'll look for a confirmation of the signal as we move throughout the year.
So that's one.
And secondly.
There is emerging evidence.
Presented and published late last year that treatment pull Victor might actually sensitize, the tumor microenvironment to checkpoint.
Target therapy.
And this.
This all has to be proven out in the clinic with in larger studies and step one for US is still declining what we think the clinical profile is of dialed mab monotherapy for these heavily.
Treated.
Patients with measurable disease.
But once we understand that.
There's a number of options how to move forward in an intelligent manner for development of this drug. So we're excited for what we're seeing again early days here. So we're we don't want to.
Get over our skews, but.
We will look for a confirmation of the signal as we move throughout the year.
Dane Leone: Great, thank you. Thank you for your question. One moment, please. Our next question comes from the line of Alex Stranahan from Bank of America. The floor is yours.
Great. Thank you guys.
Thank you for your question one moment please.
Our next question comes from the line of Alex Stranahan from Bank of America. The floor is yours.
Operator: Hey, guys. Thanks for taking the question. This is John. I'm on behalf of Alec.
Okay.
Hey, guys. Thanks for taking the question this is John and mantra Alec.
Unnamed: Just a first quick question. I think this was briefly mentioned before, but just wanted to check. I didn't catch everything.
Just a first quick question I think this was briefly mentioned before but just wanted to check I didn't catch everything but it won't be like a good benchmark comparator for us to look at.
Unnamed: But what would be a good benchmark or a comparator for us to look at, you know, in comparison to the Wudaliband monotherapy data presented today? That's my first question. Second question on, you know, like quality of life data, you know, when can we expect to see some color regarding that if you're, you know, keeping track of it? And could you maybe provide some, shed some light on, you know, what you're currently observing in the clinic in terms of quality of life and, you know, some patient-reported outcomes? Thanks. Thank you. Yeah, we're not collecting them.
In comparison to the dialogue.
Therapy data presented today.
That's my first question second question.
On.
Quality of life data.
When can we expect to see some color regarding that if you're keeping track of it could you maybe provide some shed some light on what you're currently observing in the clinic in terms of quality of life.
Some are patient reported outcomes.
Thank you.
Dane Leone: Oh, sorry, Dan, you want to take both of them or not? Yeah, I think, I mean, that question is really a question of when we have the totality of a cohort and discussion with our clinical investigators, is the clinical experience overall for these patients something that we should move forward with? And, you know, so to that effect, the totality of the data, we don't know at this point, right? We want to see, hopefully, 30 patients in each of these cohorts, the monotherapy cohort and the distact combination cohort, to have that conversation with our clinical investigators. So it's a great question, and that's really what we're hoping to answer. In terms of the first part of the question, you know, that's why we provided the data table and the slides, because each of these studies that we're looking at, or peer studies, are exciting, right?
We're not collect Oh, sorry, Dan you want to take both of them are yes, I think I mean, the question is really a question of when we have a totality of the cohort and discussion with our clinical investigators.
Is that clinical experience overall for these patients something that we should move forward.
And so.
So to that effect the totality of the data we don't know at this point right. We want to see hopefully 30 patients in each of these cohorts the monotherapy cohort in the Docetaxel combination cohort.
To have that conversation.
With our clinical investigators so that's a great question and that's really why we're hoping to answer.
In terms of the first part of the question.
That's why we provided the data table in the slides because each of these studies that we're looking at our peer studies are exciting right. We're excited about value or at a Meg and the clinical response, there, but they're also limited in terms of their size and their scope and the comparability of the patients.
Dane Leone: We're excited about thaluritamig and the clinical response there, but the trials are limited in terms of their size and their scope and the comparability of the patients that were enrolled. So, we don't want to make apples to oranges comparisons of novel agents for the treatment of these prostate cancer patients right now. But, you know, I think what we could say is a number of these programs, thaluritamig, I think, is undeniable, and hopefully, our VDAL-MAB monotherapy program as well, seem to be surpassing what you could probably expect for late-line chemotherapy from contemporary studies, as we mentioned, the composite taxable response rates in the Checkmate 650 study and the therapy study. And then, once you get to earlier lines of therapy, I think it is, you know, that toxicity profile.
Were enrolled.
So we don't want to make apples and oranges comparisons of of novel agents.
For the treatment of these prostate cancer patients are right now.
But I think what we could say is a number of these programs.
The value of Red Omega I think is undeniable and hopefully are put out by a monotherapy program as well seem to be surpassing what you could probably expect for a late line chemotherapy from contemporary studies as we mentioned the kebabs attacks or response rates.
And the Checkmate <unk> study and the therapy study.
And then once you get to earlier lines of therapy I think it is toxic.
Dane Leone: And again, you know, if it does seem that Plevicto is sensitizing the tumor microenvironment for IO therapy, we have a therapy that does not have overlapping heme tox and could be an, you know, an interesting idea to explore down the road. All right. Thanks, PhotoColor. Thank you for your question. One moment, please. Our next question comes from the line of Tara Bannacroft from TD Cowen. The line is now yours. Hi, good afternoon.
Toxicity profile and again.
If it does seem that victoza is.
Sensitizing, the tumor microenvironment for Io therapy.
We have a therapy that does not have overlapping heme tox.
And could be.
And an interesting idea to explore down the road.
Yeah.
Alright, thanks for the color.
Thank you for your question one moment please.
Okay.
Our next question comes from the line of Tara Bancroft from TD Cowen. Your line is now yours.
Hi, Good afternoon. So my question is.
Tara Bannacroft: So my question is, general questions. So are there any other combos besides chemo that you're considering or really excited about that could increase the robustness of this data? Then, specifically referring to chemo, how do you think safety will look in that combination? Is there any update that you can provide on how that's going now in the 1704 study? Thanks.
More of a general question. So are there any other combos. Besides chemo that you're considering are really excited about that could increase the robustness of this data and.
Then.
In <unk>.
Specifically, referring to the chemo combo.
How do you think safety will look and that combination is there any update that you can provide on how that's going now into 17 O. Four study. Thanks.
Bassil I. Dahiyat: So I guess on the first one, other combos other than chemo, we think chemo is a very important one in this setting because it is still the predominantly used therapy post-androgen therapy. I think it's really interesting to imagine post-plevicto treatment, maybe not in concert, given the intriguing immune priming activity that plevicto perhaps has from some small studies recently published, I think out of UCSF. So I think those are the two top things on our mind now. But I think in the future, as we see our CD28 technology evolve, our XMAB808 program is, of course, aimed partially, at least, at prostate cancer, maybe even predominantly at the moment. And as that one evolves in combination with Pembro, we're certainly keeping our eye on how to maybe use that with Vudalabab if the stars align, right?
So I guess on the first one or other companies other than it came but we think he was a very important one in this setting because it is the <unk>.
Dominantly used therapy post androgens still I think it's really interesting to imagine post <unk> treatment may be not in concert given the intriguing immune priming activity that <unk>, perhaps has from some small studies recently published and they've Gotta UCSF.
I think those are the two top things on our mind now, but I think in the future as we see our CD.
CD 28 technology of all of our <unk> program is of course aimed partially at least add prostate maybe even predominantly at the moment and as that evolves in combo with pember, we're certainly keeping our eye on how to maybe use that.
Bassil I. Dahiyat: So that's maybe the other big one that we're thinking of. You know, the future might hold combinations with CD3 bispecifics with molecules like Fudalimab. I think that's something people are looking at. They're just starting to happen in the clinic now. I'm aware of some CD3 solid tumor molecules that are being tested with checkpoints. That's maybe a little bit further off in the future, though.
With good Alabama, if the stars align right. So so that's maybe the other other big one that we're thinking of.
The future might hold combinations with CD three.
Our bi specifics with with molecules like <unk> I think that's something people are looking at they're just starting to happen in the clinic now I'm aware of some CD three solid tumor molecules that are being tested with checkpoints, that's maybe a little bit further off in the future though.
Nancy Valenti: And then I guess your second question was about what we can say about safety from the ongoing O4 study, given that we're not, you know, sharing specific data. So maybe, Nancy, do you want to comment? Yeah, absolutely. So maybe I can share also that since we last presented data, we amended the protocol, the combination protocol for prostate cancer, to remove carboplatin in all but the aggressive variant. And we're really focused on the taxanes, specifically docetaxel, as first-line chemotherapy. And so far, based on feedback from investigators, we seem to be seeing better tolerability with these new regimens than the prior ones. Operator. Do we have any other questions? No, that looks like it's Clint.
And then I guess your your second question was on what can we say about safety from the ongoing <unk> four study given that we're not sharing specific data. So maybe Nancy do you want to comment yeah, absolutely. So maybe I can share also that since we last presented data we amended the protocol.
The combination protocol in prostate cancer to remove the carboplatin and all but the aggressive variant and we're really focused on the taxane, specifically docetaxel as first line chemotherapy.
So far based on feedback from investigators we seem to be seeing better tolerability.
With.
These new regimens in the prior one.
Operator.
We have any other questions.
Operator: Great, well, thanks everybody for joining us today, and have a wonderful evening. We look forward to our next update. Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
Now that looks like that's it.
Great well, thanks, everybody for joining us today and have a wonderful evening and we look forward to our next update.
Thank you for participation today's conference. This does conclude the program you may now disconnect.
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