Q1 2022 Xencor Inc Earnings Call

May 5, 2022

[music].

Yes.

Good afternoon, ladies and gentlemen, and thank you for standing by, and welcome to the Xencor's first quarter 2022 conference call. At this time, all participants are in a listen-only mode.

Good afternoon, ladies and gentlemen, and thank you for standing by and woke up to the <unk> first quarter 2022 conference calls at this time all parties spots that are in a listen only mode. After the speaker's presentation. There will be a question and answer session. Please be advised that this call is being <unk>.

I would now like to turn the call over back to Basil Daya.

After the speaker's presentation, there will be a question and answer session.

Please be advised that this call is being recorded at the company's request.

Recorded at those companies to quest now.

Now I would like to turn the call over to our speaker today, Charles Liles, Head of Corporate Communications and Investor Relations.

Thanks very much for joining us today, everybody, and we look forward to updating you again, in the near future.

Now I would like to turn the call operator speaker today.

Josh <unk> head of corporate Communications and Investor Relations. Please go ahead.

Please go ahead, who will join us when we open up the call for your questions after prepared remarks.

Thank you and good afternoon earlier today, we issued a press release, which outlines the topics we plan to discuss today. The press release is available at Www Dot <unk> Dot Com with me on the call are <unk>, President and Chief Executive Officer, Allen Yang Chief Medical Officer, John Kush, Chief Financial Officer, and John <unk>, Chief Scientific Officer will join us.

Let me open up the call for your questions. After our prepared remarks before we begin I would like to remind you that during the course of this conference calls and core management may make forward looking statements, including statements regarding the company's future financial and operating results future market conditions, the plans and objectives of management and future operations. The company's partnering efforts capital requirements product offerings and research and development Pro.

Before we begin, I would like to remind you that during the course of this conference call, Xencor management may make forward-looking statements, including statements regarding the company's future financial and operating results, future market conditions, the plans and objectives of management, future operations, the company's partnering efforts, capital requirements for product offerings, and research and development programs.

Bye-bye.

This concludes today's conference call. You may now disconnect.

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. The outcome of the 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 recently filed annual report on Form 10-K and quarterly report on Form 10-Q.

Thank you.

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 some of the 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 recently filed annual report on Form 10-K, and quarterly report on Form 10-Q.

With that, let me pass the call over to Basil.

That let me pass the call over to Basil Thanks, Charles and good afternoon, everyone continuing with the approach we took last quarter, we're going to make a few brief comments before spending the majority of today's call or questions.

Thanks, Charles, and good afternoon, everyone.

Continuing with the approach we took last quarter, we're going to make a few brief comments before spending the majority of today's call on questions.

So.

So, as I like to usually open with, we've used our array of modular approach and engineering tools to create a broad internal development portfolio, in oncology and autoimmune diseases, which allows us to take multiple simultaneous shots on goal in the clinic.

I'd like to usually open when we've used our array of modular approach to engineering tools to create a broad internal development portfolio in oncology and autoimmune diseases, which allows us to take multiple simultaneous shots on goal in the clinic.

Our intent remains to use proof-of-concept data from these early-stage studies to guide which programs we advance, which we terminate, and which we partner, so that we're most efficiently using our cash and our employees' time.

Our intent remains to use proof of concept data from these early stage studies to guide, which programs, we advance, which we terminate in which we partner so that we're most efficiently using our cash and our employees.

In a moment, Alan is going to review our advancing clinical programs and upcoming plans.

Good afternoon, ladies and gentlemen, and thank you for standing by, and welcome to, the Xencor's first quarter 2022 conference call. At this time, all participants are in a listen-only mode.

In a moment Alan is going to review, our advancing clinical programs and upcoming plans, but first today, we announced our plan to terminate internal development of two phase one programs <unk>, one and tight you to map, which focuses our resources on those clinical programs of ours with the greatest potential for success and makes room in our portfolio for the next wave of <unk> bi specifics in engine.

But first, today we announced our plan to terminate internal development of two Phase I programs, XMAB-A41 and Tidudumab, which focuses our resources on those clinical programs of ours with the greatest potential for success and makes room in our portfolio for the next wave of XMAB bi-specifics and engineered cytokines. For Tidudumab, our SFTR2 by CD3 bi-specific antibody, and XMAB-A41, our CHLA4 by LAG3 bi-specific antibody, after reviewing the data generated to date, we believe that neither program has a competitive enough clinical profile in their respective areas, particularly when compared to the programs we are currently advancing.

After the speaker's presentation, there will be a question-and-answer session.

Please be advised that this call is being recorded at the company's request.

Cytokines for <unk> or <unk> by CD three by specific antibody.

Next let me for one or <unk> four by lag three bispecific antibody. After reviewing the data generated to date, we believe that neither program has a competitive enough clinical profile in their respective areas, particularly when compared to the programs. We are currently advancing.

So, we're going to keep supporting patients currently enrolled in the study, including by continuing to provide study drugs.

So we're going to keep supporting patients currently enrolled in this study, including by continuing to provide study drug.

Now, a core piece of our strategy is leveraging our plug-and-play XMAB FC domain through licensing transactions, especially in therapeutic areas outside of our core focus on oncology and autoimmune disease.

Now a core piece of our strategy is leveraging our plug and play <unk> FC domain through licensing transactions, especially in therapeutic areas outside of our core focus on oncology and autoimmune disease. We wanted to highlight the recent FDA approval for Lexi on Astrazeneca Ultra mirrors for adult patients with generalized myasthenia gravis its third approval in the U S.

We wanted to highlight the recent FDA approval for Lexion AstraZeneca's Ultramiris for adult patients with generalized myasthenia gravis, its third approval in the U.S. Ultramiris, of course, incorporates our Xtend FC domain for longer half-life.

Now, I, would like to turn the call over to our speaker today, Charles Liles, Head of Corporate Communications and Investor Relations.

Thank you and good afternoon.

Altamira So of course incorporates our extend FC domain for longer half life.

We also bolstered a cash position with over $70 million in royalty revenue this quarter for the COVID antibodies to Trovimab, which incorporates the same Xtend FC domain from our partners Vir and GSK. Though, because of the rapidly shifting COVID variants that keep emerging, we expect this revenue to drop very substantially next quarter and beyond.

Earlier today, we issued a press release which outlined the, topics we plan to discuss today. The press release is available at www.xencor.com.

We also bolstered our cash position with over $70 million in royalty revenue this quarter for the Covid antibody <unk>, which incorporates the same extend FC domain.

From our partners Vir and GSK.

Though because of the rapidly shifting COVID-19 variants that keep emerging we expect this revenue to drop very substantially next quarter and beyond.

Now, looking at our partnerships for the XMAB BISPECIFIC FC domain in our T-Cell Engager, Toolkit, last quarter we highlighted encouraging early clinical data from Amgen's AMG509 program in prostate cancer, which in addition to being an XMAB BISPECIFIC, uses the XMAB, 2 plus 1 multivalent format for T-cell engagement.

Now looking at our partnerships for the <unk> Bispecific FC domain and our T cell engage your toolkit last quarter, we highlighted encouraging early clinical data from Amgen's AMG 509 program in prostate cancer, which in addition to being an ex net by specific uses the <unk> to plus one multifamily format for T cell engagement.

Now within the past quarter, Astellas' ASP2138, an XMAB Cloudin 18.2 by CD3 BISPECIFIC antibody, has advanced into clinical development for patients with gastric, gastroesophageal, and pancreatic cancers, and we look forward to following this program, too.

Now within the past quarter Astellas is asps to 138, and <unk> cloud and $18 two by CD three by specific antibody has advanced into clinical development for patients with gastric gastroesophageal and pancreatic cancers and we look forward to following this program too.

Now I'm going to turn it over to Allen Yang Our Chief Medical Officer, who is going to briefly review, our clinical programs and upcoming plans.

Now I'm going to turn it over to Alan Yang, our Chief Medical Officer, who's going to, briefly review our clinical programs and upcoming plans.

With me on the call are Basil Dahiyat, President and Chief Executive Officer, Alan Yang, Chief Medical Officer, John Cush, Chief Financial Officer, and John Desjardins, Chief Scientific, Officer, who will join us when we open up the call for your questions after prepared remarks.

Before we begin, I would like to remind you that during the course of this conference, call, Xencor Management may make forward-looking statements, including statements regarding the company's future financial and operating results, future market conditions, the plans and objectives of management, future operations, the company's partnering efforts, capital requirements for product offerings, and research and development programs.

Thanks, Basil.

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. The outcome of the 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 recently filed annual report on Form, 10-K and quarterly report on Form 10-Q.

Thanks, Basel, so starting with our CD three bi specifics and promote a map our CD 20 by CD three by specific antibody that we are co developing with Janssen, we announced that the first patient has been dosed in a potentially registration, enabling phase II study, where it is being evaluated in combination with tap a cinema plus lenalidomide in patients.

So, starting with our CD3 BISPECIFICs in Plamodimab, our CD20 by CD3 BISPECIFIC antibodies that, we are co-developing with Janssen, we announced that the first patient has been dosed in a potentially registration-enabling Phase 2 study, where it is being evaluated in combination with tafacitimab plus lenalidomide in patients with relapse or refractory diffuse large B-cell lymphoma.

With that, let me pass the call over to Basil.

Thanks, Charles, and good afternoon, everyone.

Continuing with the approach we took last, quarter, we're going to make a few brief comments before spending the majority of today's call on questions.

So, as I like to usually open with, we've used our array of modular approach and engineering tools to create a broad internal development portfolio in oncology and autoimmune diseases, which allows us to take multiple simultaneous shots on goal in the clinic.

Our intent remains to use proof-of-concept data from these early-stage studies to guide, which programs we advance, which we terminate, and which we partner, so that we're most efficiently using our cash and our employees' time.

In a moment, Alan is going to review our advancing clinical programs and upcoming plans.

But first, today we announced our plan to terminate internal development of two Phase I programs, XMAP-A41 and TI-DUDAMAP, which focuses our resources on those clinical programs of ours with the greatest potential for success and makes room in our portfolio for the next wave of XMAP bispecifics and engineered cytokines. For TI-DUDAMAP, our SFTR2 by CD3 bispecific antibody, and XMAP-A41, our CHLA4 by LAG3, bispecific antibody, after reviewing the data generated to date, we believe that neither program has a competitive enough clinical profile in their respective areas, particularly when compared to the programs we are currently advancing.

So, we're going to keep supporting patients currently enrolled in the study, including by continuing to provide study drugs.

Now, a core piece of our strategy is leveraging our plug-and-play XMAP FC domain through licensing, transactions, especially in therapeutic areas outside of our core focus on oncology and autoimmune disease.

We wanted to highlight the recent FDA approval for Lexion AstraZeneca's Ultramiris for adult, patients with generalized myasthenia gravis, its third approval in the U.S. Ultramiris, of course, incorporates our Xtend FC domain for longer half-life.

We also bolstered a cash position with over $70 million in royalty revenue this quarter, for the COVID antibody citrovimab, which incorporates the same Xtend FC domain from our partners, Vir and GSK.

With relapsed or refractory diffuse large b cell lymphoma note. We are conducting this particular study ourselves and our partners more focus and insight are providing top of pseudo map. The study has two parts. The first of which is the safety run in followed by a planned randomization between the triple combination of <unk> map lenalidomide with or without.

So because of the rapidly shifting COVID variants that keep emerging, we expect this revenue, to drop very substantially next quarter and beyond.

Now looking at our partnerships for the XMAB bispecific FC domain in our T-cell engager, toolkit, last quarter we highlighted encouraging early clinical data from Amgen's AMG509 program in prostate cancer, which in addition to being an XMAB bispecific, uses the XMAB 2 plus 1 multivalent format for T-cell engagement.

Now within the past quarter, Astellas' ASP2138, an XMAB Cloudin 18.2 by CD3 bispecific antibody, has advanced into clinical development for patients with gastric, gastroesophageal, and pancreatic cancers.

Note, we are conducting this particular study ourselves, and our partners, Morphosis and, Insight, are providing tafacitimab. The study has two parts, the first of which is a safety run-in followed by a planned randomization, between the triple combination of tafacitimab, lenalidomide, with or without Plamodimab.

And we look forward to following this program, too.

Promote them out later this year, we plan to present data from the expansion cohorts in the ongoing phase one IV monotherapy study. In addition, we also plan to introduce subcutaneous dosing into this study.

Later this year, we plan to present data from the expansion cohorts in the ongoing, Phase 1 IV monotherapy study. In addition, we also plan to introduce subcutaneous dosing into this study.

Also for our <unk> III platform soon we anticipate dosing the first patient in a phase one study evaluating our <unk> three targeting CD three by specific antibody ex map 809 in patients with renal cell carcinoma, we're particularly excited about 809, which utilizes the multivalent ex map too.

Also, for our CD3 platform, soon we anticipate dosing the first patient in a Phase 1 study, evaluating our ENPP3 targeting CD3 BISPECIFIC antibody, XMAB819, in patients with renal cell carcinoma.

We're particularly excited about 819, which utilizes the multivalent XMAB2 plus 1 format. In preclinical studies, we have shown this format preferentially kills tumor cells with, high-target antigen expression relative to normal cells, which may be of particular benefit against solid tumors.

Plus one format in preclinical studies, we have shown this format preferentially kills tumor cells with high target antigen expression relative to normal cells, which may be of particular benefit against solid tumors.

Moving onto our tumor microenvironment activator bi specifics, our most advanced <unk> with Allomap, which targets PD, one and <unk> four double positive lymphocytes.

Moving on to our tumor microenvironment activator BISPECIFICs, our most advanced is Vudalimab, which targets PD-1 and CTLA-4 double-positive lymphocytes.

We are conducting two Phase 2 studies, the first of which is enrolling patients with, metastatic castrate-resistant prostate cancer. In this study, Vudalimab is being evaluated as a monotherapy or in combination regimen, with standard of care, depending on the tumor's molecular subtype.

We're conducting two phase III studies, the first of which is enrolling patients with metastatic castrate resistant prostate cancer.

In this study with Allomap is being evaluated as a monotherapy or in combination regimen with standard of care, depending on the tumors molecular subtype. We're also initiating a second study in patients with certain.

We're also initiating a second study in patients with certain gynecological malignancies or, clinically-defined high-risk metastatic castrate-resistant prostate cancer.

Gynecological malignancies, or clinically defined high risk metastatic castrate resistant prostate cancer and we're supporting additional signal seeking investigator sponsored studies as well.

And we're supporting additional signal-seeking investigator-sponsored studies as well.

<unk> 104, our PD one by Iqos bi specific antibody is our second tumor microenvironment activator and is advancing now in expansion and the expansion portion of our phase one study in advanced solid tumors, where we are valuing it in combination with if aluminum app, we will be presenting a poster with the data of the monotherapy escalation.

XMAB104, our PD-1 by ICOSPECIFIC antibody, is our second tumor microenvironment activator, and is advancing now in the expansion portion of our Phase 1 study in advanced solid tumors, where we are evaluating it in combination with ipilimumab.

We will be presenting a poster with the data of the monotherapy escalation portion of the, study at ASCO in a few weeks from now.

<unk> portion of this study at <unk> in a few weeks from now.

Moving on to our suite of reduced potency cytokines, all engineered with our Bispecific FC domain and incorporating extend technology at the recent ACR meeting we introduced two preclinical stage programs, a decoy resistant IL 18, and the lag three targeted IL 15, which is biased towards binding inactivating lag.

Moving on to our suite of reduced-potency cytokines, all engineered with our bispecific, SC domain and incorporating Xtend technology, at the recent AACR meeting, we introduced two preclinical stage programs, a decoy-resistant IL-18 and a LAG-3-targeted IL-15, which is biased towards binding and activating LAG-3-positive T cells that are more likely to be tumor-associated.

<unk> positive T cells that are more likely to be tumor associated.

Clinically, our most advanced cytokine is XMAP306.

Clinically our most advanced cytokines as <unk> III Asics, a reduced potency long acting IL 15 FC fusion protein that we are co developing with genentech.

It reduced potency long-acting IL-15SC fusion protein that we are co-developing with Genentech.

X amount $3 six targets NK and T cells for the treatment of patients with cancer and the ongoing phase one dose escalation, we observed high levels of sustained NK cell expansion and evidence of peripheral effector T cell proliferation, and we announced last fall and we announced this last fall just recently genentech initiate.

XMAP306 targets NK and T cells for the treatment of patients with cancer. In the ongoing phase one dose isolation, we observed high levels of sustained NK cell, expansion and evidence of peripheral effector T cell proliferation.

And we announced last fall, and we announced this last fall, just recently Genentech initiated, an additional phase one study to evaluate a combination with anti-CD3 antibody daratumab in patients with relapse or refractory multiple myeloma.

Additional phase one study to evaluate the combination with anti <unk> three antibody <unk> in patients with relapsed or refractory multiple myeloma.

We ourselves are planning additional studies with XMAP306 in combination with other therapeutic, agents and look forward to providing updates in the near future.

We ourselves are planning additional studies with <unk> in combination with other therapeutic agents and look forward to providing updates.

In the near future.

Next is our wholly owned <unk> <unk> six for reduced potency IL two <unk> FC fusion cytokines, which we are developing an autoimmune disease.

Next is our wholly owned XMAP564, reduced potency IL-2FC fusion cytokine, which we are, developing in autoimmune disease.

We're conducting a single ascending dose study, phase one, in healthy volunteers, and later, this year we'll present our initial data from this study.

We're conducting a single ascending dose study.

Phase one in healthy volunteers and later this year, we will present, our initial data from this study.

In parallel, we plan to initiate a multiple ascending dose study in patients.

In parallel we plan to initiate a multiple ascending dose study in patients.

Our third cytokines to enter the clinic will be the IL 12 FC ex Mab 662 for which we anticipate filing an IND near year end.

Our third cytokine to enter the clinic will be the IL-12FC XMAP662, for which we anticipate, a filing and IND near year end.

Finally, one additional exciting program we plan to advance into the clinical development, this year is our first CD28 bispecific antibody, XMAP808, which targets the broadly expressed tumor antigen B7H3. This new class of bispecific is engineered to provide conditional CD28 co-stimulation, of T-cells, activating them when bound to tumor cells.

Finally, one additional exciting program, we plan to advance into clinical development. This year is our first CD 28 by specific antibody <unk> 808, which targets the broadly expressed tumor antigen <unk> III. This new class of bi specific is engineered to provide conditional CD 28 co stimulation of T cells activating them.

When bound to tumor cells.

Now with that, I'll hand the call over to John Cush, our CFO, to review our financial, results.

Now I'm going to turn it over to Alan Yang, our chief medical officer, who's going to, briefly review our clinical programs and upcoming plans.

Now with that I'll hand, the call over to John <unk>, Our CFO to review our financial results.

Thank you, Alan.

Thanks, Basil.

Alan <unk>.

XenCore's broad FC technologies and the multiple partnerships that we have entered continue, to provide us with opportunities to generate cash flows that strengthen our balance sheet and allow us to invest in our pipeline of bispecific antibody and engineered cytokine candidates. In the first quarter, we received $83.7 million of revenue from these partnerships. A breakdown of the proceeds includes $78.7 million in royalties and $5 million in expected, milestone payments. We'd like to point out that approximately $70 million of the royalty revenue was from, our VAER partnership and relates to sales of sultrofumab.

So starting with our CD3 bispecifics in plomodimab, our CD20 by CD3 bispecific antibody that we, are co-developing with Janssen, we announced that the first patient has been dosed in a potentially registration-enabling phase 2 study, where it is being evaluated in combination with tafacitimab plus lenalidomide in patients with relapse or refractory diffuse large B-cell lymphoma.

<unk> broad FC technologies and the multiple partnerships that we have entered continue to provide us with opportunities to generate cash flows and strengthen our balance sheet and allow us to invest in our pipeline as bispecific antibody in engineered cytokines candidates.

Note, we are conducting this particular study ourselves, and our partners, Morphosis and, Insight, are providing tafacitimab. The study has two parts, the first of which is a safety run-in, followed by a planned, randomization between the triple combination of tafacitimab, lenalidomide, with or without plomodimab.

Later this year, we plan to present data from the expansion cohorts in the ongoing phase, 1 IV monotherapy study. In addition, we also plan to introduce subcutaneous dosing into this study.

Also, for our CD3 platform, soon we anticipate dosing the first patient in a phase 1 study, evaluating our ENPP3-targeting CD3 bispecific antibody, XMAP819, in patients with renal cell carcinoma. We are particularly excited about 819, which utilizes the multivalent XMAP2 plus 1 format. In preclinical studies, we have shown this format preferentially kills tumor cells with, high-target antigen expression relative to normal cells, which may be of particular benefit against solid tumors.

Moving on to our tumor microenvironment activator bispecifics, our most advanced is Vudalumab, which targets PD-1 and CTLA-4 double-positive lymphocytes.

We are conducting two phase 2 studies, the first of which is enrolling patients with, metastatic castrate-resistant prostate cancer. In this study, Vudalumab is being evaluated as a monotherapy or in combination regimen, with standard of care, depending on the tumor's molecular subtype.

And given GSK's recent comments about anticipated sultrofumab sales for the remainder of 2022, we expect that future royalty revenue on net sales of sultrofumab will be substantially lower than first quarter amounts.

And we're supporting additional signal-seeking investigator-sponsored studies as well.

In the first quarter, we received $83 $7 million of revenue from these partnerships.

We're also initiating a second study in patients with certain gynecological malignancies or, clinically defined high-risk metastatic castrate-resistant prostate cancer.

<unk> out of the proceeds include $78 $7 million in royalties and $5 million and expected milestone payments, we'd like to point out that approximately $70 million of royalty revenue was from our beer partnership and it relates to sales of Central lab and given Gsk's recent comments about anticipates a trove mid sales for the remainder of 2022.

We expect that future royalty revenue on net sales for <unk> will be substantially lower than first quarter amount.

As noted we continue to maintain a strong balance sheet as of March 31st our cash cash equivalents receivables and marketable securities totaled $683 6 million, which is an increase over December 31 amounts of $664 1 million.

As noted, we continue to maintain a strong balance sheet. As of March 31st, our cash, cash equivalents, receivables, and marketable securities totaled, $683.6 million, which is an increase over December 31st amounts of $664.1 million.

We currently estimate ending 2022 with between $500 and $550 million in cash, cash equivalents, receivables, and marketable debt securities. Based on our current operating plans, we would expect to have cash to fund R&D programs and, operations through the end of 2025.

We currently estimate ending 2022 with between 500 $550 million in cash cash equivalents receivables and marketable debt securities.

Based on our current operating plans, we would expect to have cash to fund R&D programs and operations through the end of 2025.

I will refer to you to our press release this afternoon and our SEC filings for further, review of our financial results.

We refer you to our press release this afternoon, and our SEC filings for further review of our financial results.

With that we'd now like to open up the call for your questions operator.

With that, we'd now like to open up the call for your questions.

XMAB-104, our PD-1 by ICOSPI-specific antibody, is our second tumor microenvironment activator, and is advancing now in the expansion portion of our Phase I study in advanced solid tumors where we are evaluating it in combination with ipilimumab.

Operator?

Thank you.

Thank you at this time I would like to remind everyone in order to ask a question. Please press the financing number one.

At this time, I would like to remind everyone, in order to ask a question, please press star, then the number one on your telephone keypad.

We will be presenting a poster with the data of the monotherapy escalation portion of the, study at ASCO in a few weeks from now.

Moving on to our suite of reduced-potency cytokines, all engineered with our bispecific, SC domain and incorporating Xen technology, at the recent AACR meeting, we introduced two preclinical-stage programs, a decoy-resistant IL-18 and a LAG-3-targeted IL-15, which is biased towards binding and activating LAG-3 positive T cells that are more likely to be tumor-associated.

Please press Star then the number one on your telephone keypad.

Your first question comes from the line of Joseph Cheng from SBB Securities. Your line is now open.

Your first question comes from the line of Jonathan Cheng from SVV Securities.

Your line is now open.

Clinically, our most advanced cytokine is XMAB-306. It is a reduced-potency, long-acting IL-15 SC fusion protein that we are co-developing, with Genentech. XMAB-306 targets NK and T cells for the treatment of patients with cancer. In the ongoing Phase I dose escalation, we observed high levels of sustained NK cell, expansion and evidence of peripheral effector T cell proliferation, and we announced this last fall.

Hi, guys.

Most recently, Genentech initiated an additional Phase I study to evaluate a combination with, anti-CD3 antibody daratumab in patients with relapse or refractory multiple myeloma.

Thanks for taking my questions.

We ourselves are planning additional studies with XMAB-306 in combination with other therapeutic, agents and look forward to providing updates in the near future.

Hi, guys. Thanks for taking my questions first question on X map 104 can you help set investor expectations for the upcoming data at Ascot.

First question, on XMAP 104, can you help set investor expectations for the upcoming, data at ASCA?

Next is our wholly-owned XMAB-564 reduced-potency IL-2 SC fusion cytokine, which we are developing, in autoimmune disease.

Sure.

I'll start with that.

Sure I'll start with that thanks for the question on 104, it is going to cover our dose escalation portion of this study and the study is currently in expansion. So it's going to go to the dose escalation.

Thanks for the question on 104.

It's going to cover our dose escalation portion of the study, and the study is currently in, expansion, so it's going to go to the dose escalation of that agent where we're looking to see what kind of safe doses we can achieve.

We're conducting a single ascending-dose study, Phase I, in healthy volunteers, and later, this year, we'll present our initial data from the study.

In parallel, we plan to initiate a multiple ascending-dose study in patients.

That agent where.

We're looking to see what kind of safe doses, we could achieve we know that there's been a history of iqos agents that have had challenges there.

Our third cytokine to enter the clinic will be the IL-12 SC XMAB-662, for which we anticipate, filing an IND near year-end.

Finally, one additional exciting program we plan to advance into clinical development, this year is our first CD28 bispecific antibody, XMAB-808, which targets the broadly expressed tumor antigen B7H3. This new class of bispecific is engineered to provide conditional CD28 co-stimulation, of T cells, activating them when bound to tumor cells.

We know that there's been a history of IQOS agents that have had challenges there, and, part of the whole goal of our design is by providing selective checkpoint inhibition and co-stimulation, we can provide a different kind of profile.

Part of the whole goal of our design is by providing selective checkpoint inhibition and co stimulation. We can we can provide a different kind of profile and then of course, whatever whatever efficacy. We can we can offer it as an advanced solid tumor patients as is typical in these studies.

And then, of course, whatever efficacy we can offer.

It's an advanced solid tumor patient, as is typical in these studies.

Got it.

Got it and second question on to do the math and ex Snap 841 are you able to provide any more color on what you saw or didn't see in those studies that led to the decision to discontinue those programs.

And second question on Tadudumab and XMAP 841, are you able to provide any more color, on what you saw or didn't see in those studies that led to the decision to discontinue those programs?

Yeah, I'll open it, and then I can let Alan jump in.

Now with that, I'll hand the call over to John Cush, our CFO, to review our financial, results.

Yes ill open it and then I can let Allen jumped in what we really are trying to do with our strategy that we've been executing now for several years has put a number of programs that have promising biology into phase one and uses data to judge which ones could have the characteristics that we could develop and potentially create a.

What we really are trying to do with our strategy that we've been executing now for several, years is put a number of programs that have promising biology into phase one and use the data to judge which ones can have the characteristics that we could develop and potentially create our own drug with or partner in a way that we think is very valuable.

Thank you, Alan.

And given GSK's recent comments about anticipated siltropimab sales for the remainder of 2022, we expect that future royalty revenue on net sales of siltropimab will be substantially lower than first quarter amounts.

As noted, we continue to maintain a strong balance sheet. As of March 31st, our cash, cash equivalents, receivables, and marketable securities total $683.6 million, which is an increase over December 31st amount of $664.1 million. We currently estimate ending 2022 with between $500 and $550 million in cash, cash equivalents, receivables, and marketable debt securities.

Based on our current operating plans, we would expect to have cash to fund R&D programs and operations through the end of 2025.

I will refer you to our press release this afternoon and our SEC filings for further review of our financial results.

Our own drug with or partner in a way that we think is very valuable.

And so we're always looking at the efficacy versus the competitive landscape, which is always shifting and so this was done in the context of that and judging whether our resources could be better spent on other of our programs, who who's competitive profiles are more attractive so it's about safety and efficacy in the particular context.

And so we're always looking at the efficacy versus the competitive landscape, which is, always shifting.

And so this was done in the context of that and judging whether our resources could be, better spent on other of our programs whose competitive profiles are more attractive.

So it's about safety and efficacy in the particular context.

I would say I'll pass it over to Alan now, but in general the efficacy bar for both of those settings is fairly high and that tended to be what drove our thinking.

I would say I'll pass it over to Alan now, but in general, the efficacy bar for both, of those settings is fairly high, and that tended to be what drove our thinking.

With that, we would now like to open up the call for your questions.

Operator?

Thank you.

At this time, I would like to remind everyone, in order to ask a question, please press star then the number 1 on your telephone keypad.

Yeah, Jonathan, I'd like to say, you know, probably the things to consider were actually, outside the program.

Your first question comes from the line of Jonathan Cheng from SVV Securities.

Yes, Jonathan I would like to say.

Probably the things to consider where actually outside the program. So if you look at <unk> 841 up do lag. The BMS like three was approved it was a pretty involved the development program just for relapsed refractor excuse me for melanoma and so when you look at ex map for one comparing it to our internal pipeline, we just thought we would.

Your line is now open.

Hi, guys.

So if you look at XMAP841, Abdullag, the BMS-LAG3 was approved.

Thanks for taking my questions.

It was a pretty involved development program just for melanoma.

First question on XMAB 104.

Can you help set investor expectations for the upcoming data at ASCA?

And so when you look at XMAP841 comparing it to our internal pipeline, we just thought, we would deprioritize it. There are better things to invest in in our internal pipeline.

Sure.

Deep prioritize if there are better things to invest in our internal pipeline likewise for <unk>.

Likewise, for Tidudumab, you know, I think the key thing that changes, Amgen has AMG757, in small cell lung cancer, which is showing good clinical activity and a good safety profile.

I'll start with that.

Thanks for the question on 104.

The key thing that changes the Amgen has AMG 757 in small cell lung cancer, which is showing good clinical activity and a good safety profile and then looking at our internal pipeline again, just cant compare what we want to invest in so I think we decided to terminate that program as well.

It's going to cover our dose escalation portion of the study, and the study is currently in expansion, so it's going to go to the dose escalation of that agent where, you know, we're looking to see what kind of safe doses we could achieve.

We know that there's been a history of IQOS agents that have had challenges there, and part of the whole goal of our design is by providing selective checkpoint inhibition and co-stimulation, we can provide a different kind of profile.

And then looking at our internal pipeline, again, we just can't compare what we want, to invest in.

And then, of course, whatever efficacy we can offer.

It's in advanced solid tumor patients, as is typical in these studies.

Got it.

So I think we decided to terminate that program as well.

And second question on TODO-MAB and XMAB 841.

Are you able to provide any more color on what you saw or didn't see in those studies that led to the decision to discontinue those programs?

I'll note that there is investigator-initiated studies that we expect for at least one, if, not both, of those.

Note that there is investigator initiated studies that.

And that we expect for at least one if not both of those it will certainly support those with drug supply.

And we'll certainly support those with drug supply and, you know, see if patients can, benefit and if good experiments can be done.

And see if patients can benefit and if good experience from.

But from an internal investment perspective, it's really about where we get the most bang, for the buck.

From an internal investment perspective, it's really about where we get the most bang for the Buck.

Can you discuss the rationale for the XMAPS 306 Clostridium-Tumumab combination and multiple, myeloma?

Understood makes sense.

Just last question from me can you discuss the rationale for the X snaps 306 cluster Derek MAPP combination in multiple myeloma.

Sure.

Yeah, I'll open it, and then I can let Alan jump in.

Why don't we let John Desjardins, our CSO, take that one.

Sure why don't we let.

John did hear lay our CSO take that one he is calling in remote Johnny there.

He's calling in remote.

John, are you there?

Yeah.

Yes, yes happy to take that yes, thanks, Jonathan.

Happy to take that.

Yeah, thanks, Jonathan.

What we really are trying to do with our strategy that we've, you know, we've been executing now for several years is put a number of programs that have promising biology into Phase I and use the data to judge which ones could have the characteristics that we could develop and potentially create our own drug with or partner in a way that we think is very valuable.

You know, I think what it comes down to is Darzalex, you know, seems to have a pretty, strong NK-mediated activity against myeloma.

And so we're always looking at the efficacy versus landscape, which is always shifting.

And so this was done in the context of that and judging whether our resources could be better spent on other of our programs whose competitive profiles are more attractive.

I think what it comes down to us.

Darko Lex.

Seems to have a pretty strong NK mediated activity against myeloma.

But there is another wrinkle in it.

But there's another wrinkle in it because there's, you know, some – a small amount, of CD38 on the NK cells that actually takes a hit on the NK cells as well.

Because there is.

Some small amount of $3 38 on the NK cells that actually takes a hit on the <unk> sales as well and so the hypothesis is that with our ability with 306 to massively expand the NK cells.

And so the hypothesis is that with our ability with 306 to massively expand the NK cells, there might be additional synergy there on both fronts, right? Just having more NK cells to do the job, but also being able to replenish any of the NK, cells that Darzalex takes out.

Understood.

<unk> be additional synergy there on both fronts right just having more and can you tell us to do the job, but also being able to replenish any of the NK cells with Douglas.

Thanks Al.

Thanks for taking the questions.

Understood. Thanks for taking the questions.

Thank you.

Thank you. Your next question comes from the line of Mara Goldstein from Mizuho. Your line is now open.

Your next question comes from the line of Mara Goldstein from Mizzou.

So it's about safety and efficacy in the particular context.

Your line is now open.

I would say I'll pass it over to Alan now, but in general, the efficacy bar for both of those settings is fairly high, and that tended to be what drove our thinking.

Hi.

Yeah, Jonathan, I'd like to say, you know, probably the things to consider were actually outside the program.

So if you look at XMAP841, Abdullag, the BMS-LAG3 was approved.

Hi, Hi, digital platform Mara Goldstein I have a question on the pie the pie.

This is Suphoat from Mara Goldstein.

It was a pretty involved development program just for melanoma.

And then looking at our internal pipeline, again, you just can't compare what we want to invest in.

And so when you look at XMAP841, comparing it to our internal pipeline, we just thought we would deprioritize it. There are better things to invest in in our internal pipeline.

I have a question on the cytokine program.

Likewise, for Tidutimab, you know, I think the key thing that changes is Amgen has AMG757 in small cell lung cancer, which is showing good clinical activity and a good safety profile.

So I think we decided to terminate that program as well.

Prototype program basically I'm curious to hear your thoughts on the <unk> targeting approach My cytokine Therapeutics now you did show good data on <unk>.

Basically, I'm curious to hear your thought on the cis-targeting approach for cytokine, therapeutics.

I'll note that there is investigator-initiated studies that we expect for at least one, if not both, of those.

And we'll certainly support those with drug supply and, you know, see if patients can benefit and if good experiments can be done.

Now, you just showed the data on LAG3, IL-15 bispecific at the ACR, and, you know, whether, you have enough evidence to say that this approach is potentially safer and more effective and could be incorporated into your clinical program, you know, in the near future?

Yes.

Whether you have enough evidence to say that it's approaching potentially safer and more effective and it could be incorporated into your clinical program in the near future.

Thank you.

Thanks Al.

I'll touch on the – how we're thinking about it from a development pipeline standpoint.

But from an internal investment perspective, it's really about where we get the most bang for the buck.

On the how we're thinking about it from a development pipeline standpoint. It is in our what we call. Our early our early development considerations. We are advancing a number of the activities, we would need and we have not yet publicly guided on expectations for timing of that being in the clinic.

It's in our – what we call, you know, our early development considerations.

We're advancing a number of the activities we would need, and we've not yet publicly, guided on expectations for timing of that being in the clinic.

As to the scientific rationale I think it's fantastically strong and John can go over that in a second but really until you are in the clinic with these brand completely brand new MLA as you really don't know much.

You know, as to the scientific rationale, I think it's fantastically strong, and John, can go over that in a second, but, really, until you're in the clinic with these brand, – completely brand-new MOAs, you really don't know much.

Can you discuss the rationale for the XMAB-306 Clostridium-Tumumab combination and multiple, myeloma?

Sure.

Why don't we let John Desjardins, our CSO, take that one.

Yeah.

Yes.

And, you know, I'll add to that.

Yes on the targeting.

Yeah.

On the CIS targeting, you know, the basic idea is we started with an IL-15-LiCAX-SNAP-306, which is, you know, vastly potency-reduced, and then, when we format into that – that arm into a single-chain IL-15 RL fusion and then target it with LAG3, it's a little bit further reduced.

The basic idea is we started with.

All 15 like snap three six which is <unk>.

<unk> reduced.

And then when we format into that into that arm into a single train.

Fusion.

And then targeting lag three it's a little bit further reduced so basically when you we use that fifth avidity effect the lag three targeting <unk> positive T cells effectively restrict this activity only to that lagged <unk> positive T cell population and the hypothesis, which is supported by.

So, basically, when you – we use that CIS avidity effect, the LAG3 targeting on those, – the LAG3-positive T-cells effectively restricts its activity only to that LAG3-positive T-cell population, and the hypothesis, which is supported by all kinds of literature, including, you know, very recent papers from Steve Rosenberg's lab, is that LAG3 is a very good marker of neoantigen-reactive CD8-positive T-cells.

All kinds of literature, including very recent papers from Steve Rosenberg's lab.

At lag three is a very good marker of neo antigen reactive CDA positive T cells.

And so if we could just collectively zero in on that particular population.

And so, if we could just selectively zero in on that particular population, that really, could potentially open up a very strong therapeutic index for athletics.

That really could potentially open up a very strong therapeutic index for cytokine.

If you may just sneak one in on the 306 combination, any additional color you could provide on, that one in terms of indications or potential combination partners, any chance that you would explore a combination with NK or T cell therapy?

Got it and if I may just sneak one in on the <unk> combination any additional color you could provide on background and some indications all potential.

Thank you.

Combination partners any chance that you could.

Would explore combination with NK and T cell therapy. Thank you.

So just to recall that molecule, ExMED 306, our engineered potency L15 is in a co-development, collaboration with Genentech.

So just recall that molecule that 306 are.

Our engineered potency as <unk> is in a co development collaboration with Genentech.

You know, it's a 55-45 worldwide split, and both companies have the right to initiate, studies.

It's a $55 45 worldwide split and both companies have the right to initiate studies, we plan on initiating studies.

We plan on initiating studies, and we're in the stage of sort of really ramping one, up right now to get going, and we'll disclose details about that later.

We're in the stage of sort of really ramping up right now to get going we will disclose details about that later, but I think both T cell and NK cell mechanisms are important to explore in both.

But I think both T cell and NK cell mechanisms are important to explore in both.

We fully expect genentech to expand beyond what they're already doing with the <unk> combos, and now Dara combos and Youll hear more from <unk> as for the cell therapies of course, that's an issue where we engineer <unk> have to have a basic meeting of the minds on what programs were are going to be advanced by.

We fully expect Genentech to expand beyond what they're already doing with the Tezolizumab, combos and now Dara combos, and you'll hear more from Xencor.

As for the cell therapies, of course, that's an issue where we in Genentech have to have, a basic meeting of the minds on what programs are going to be advanced by the two companies, and so that's one where I think we're going to have to guide on that later on specifics.

By the two companies and so that's one where I think we are.

We're going to have to guide on that later on specifics I think there's a great potential for these exogenous IL 15, and exogenous cytokine approaches with cell therapy.

I think there's a great potential for these exogenous IL-15 and exogenous phytochrome, approaches with cell therapy scientifically.

Typically I just don't think we can talk about any kind of concrete plans yet.

I just don't think we can talk about any kind of concrete plans yet.

Got it.

Got it got it thank you so much.

Thank you so much.

Your next question comes from the line up Dane Leone from Raymond James Your line is now open.

Your next question comes from the line of Dane Leon from Raymond James.

He's calling in remote.

Your line is open.

John, are you there?

Hi.

Yeah.

Alright, Thank you and congrats on all the progress.

Thank you, and congrats on all the progress.

Happy to take that.

Maybe I will use my question and focus on.

I will use my question and focus on the expected initial data on Ludelumab in the back part, of the year.

Yeah, thanks, Jonathan.

You know, I think what it comes down to is Darzalex, you know, seems to have a pretty, strong NK-mediated activity against myeloma.

But there's another wrinkle in it because there's, you know, some – a small amount, of CD38 on the NK cells that actually takes a hit on the NK cells as well.

The expected.

Initial data on Allomap.

In the back part of the year. So we saw it we saw interesting data.

So, we saw interesting data in MCR-PC, I think, last year, if my memory serves me correctly, and it seems like you guys established the premise that for what had been previously tested with, I think, PD-1 and C-TIL-A4 in a similar patient population, you're achieving similar results, albeit maybe with less toxicity.

Sure.

MTR PC I think last year, if my memory serves me correctly.

And.

It seemed like you guys establish the premise that for what had been previously tested with I think PD one <unk> four in a similar patient population.

Similar results, albeit maybe with less toxicity.

What do you what are you going to be looking for from this initial.

What are you going to be looking for from this initial data from the Phase 2 study, and then how specific you can get in terms of, like, the scale and scope of that data set?

Data from the Phase two study and then spin.

Specific you can get in terms of like the scale and scope.

Of that dataset I think it would be helpful to set expectations. Thank you.

I think it would be helpful to set expectations.

Thank you.

Yeah.

Before I pass this to Alan, I'll say I recall we started this study just very late last, year.

Before I pass it to Allan ill say recall, we started the study.

Just very late last year, so by data cutoff for second half.

So, by data cutoff for second half, and it was last year, we had the MCR-PC data.

It was last year's sits here, we had the the <unk> data by getting cut off we should probably have about I don't know seven or eight months.

By data cutoff, we should probably have about, I don't know, seven or eight months of accrual, and so it'll be on the order of a few handfuls of patients that we can show, and I think really key here is, like you alluded to, that safety-efficacy balance, because recall, this study is in combo with chemo and potentially PARPs based on molecular subtypes, so can we start building on this as a backbone?

Accrual and so it'll be it'll be on the order of a few handfuls of patients that we can show and I think really key here is like you alluded to that safety efficacy balanced because recall. This study is in combo with chemo.

Potentially parks based on molecular subtypes. So can we start building on this as a base a backbone.

Yeah, Basil, not much to add.

Yeah, not much to add I would just say that a lot of our work is sort of based on previous work from Perm Bro and knee, though I think the early data showed that there was a benefit combining PD one with <unk> four but it's challenging to do that and so we're very encouraged by our early data in our phase one, which we reported 60, where we have.

I'll just say that, you know, a lot of our work is sort, of based on previous work from Pembro and Nevo.

You know, I think the early data showed that there was a benefit in combining PD-1 with CTLA-4, but it's challenging to do that.

And so we were encouraged by our early data, you know, in our phase one, which we reported, CITSI, where we have a moderate response rate, even though it was a small number of patients.

A moderate response rate, even though it was a small number of patients but moving forward.

But moving forward, you know, I think the tolerability allowed us to sort of design, a really novel study where we look at different molecular subgroups and then combine with the standard of care, right?

I think the Tolerability allowed us to sort of design, a really novel study, where we look at different molecular subgroups and then combined with the standard of care right. So you will see that data with combination of 787 with aggressive chemotherapy or a PARP inhibitor or monotherapy in different subgroups and that will hopefully.

So you'll see that data with combination of 7-1-7 with aggressive chemotherapy or PARP inhibitor or monotherapy in different subgroups, and that will hopefully bridge us to designing, you know, a registration enabling study.

Bridge us to designing a registration enabling study, yes being able to go on top of chemo would I think be a big edge here relative to the limitations you might've based otherwise and so it should be with a few handfuls of patients to get a read start to get a handle on safety see if theres any acute issues that arise and of course, we will show it.

Yeah, being able to go on top of chemo would, I think, be a big edge here relative to the, limitations you might have faced otherwise.

And so it should be, you know, with a few handfuls of patients to get a read, start to get a handle on safety, see if there's any acute issues that arise.

And, of course, we'll show whatever efficacy data we have by that point.

Ever efficacy.

You can see we data we have by that point, so I think it'll be.

So I think it'll be a solid but pretty early look.

A solid but pretty early look and know we are committed to prostate cancer. We're starting our second study, which is monotherapy in a clinically defined high risk population as well.

And note we are committed to prostate cancer.

We're starting our second study, which is monotherapy in a clinically defined high-risk population as well, along with some gynecologic tumors in a different basket in that same phase 2.

Along with some gynecologic.

Tumors in a different different basket in that same phase II, yes.

Yeah, and just to add a little bit more color on that, remember the BMS program, when they, looked at the checkmate, I believe it was the 6-5-0 study, in combination of NEVO and IPPE, the combo was better.

Just to add a little bit more color on that remember the.

The BMS program when they looked at the Checkmate I believe it was the 6650 study in combination of vivo.

But in terms of their registration phase 3, they're going, with NEVO plus chemotherapy, just dosotaxel as a single agent without the IPPE.

And it would be the combo was better but in terms of their registration phase III theyre going with Nemo, plus chemotherapy docetaxel as a single agent without the IP. So it sort of speaks to the challenges of combining PD, one with <unk> four and Thats what were looking at maybe we can do it better.

So it sort of speaks to the challenges of combining PD-1 with C-TILA-4, and that's what we're looking at.

Maybe we can do it better.

Sorry, can I just clarify one thing with you guys?

Sorry can I just clarify one thing with you guys.

Are all three arms of the study in monotherapy plus part plus chemo are those there is no no no.

Are all three arms of the study, monotherapy, plus PARC plus chemo, are those parallel?

Parallel.

So we will have.

So I'm trying to remember how much we've disclosed on clinicaltrials.gov, but we'll, have a Trials in Progress poster. And there's five arms.

I'm trying to remember how much.

Disclosed on clinical trials, but we will have a trials in progress.

I think three of them have chemo.

The poster and if Theres five arms I think three of them have chemo one of them has a PARP inhibitor and one of them is monotherapy, depending on the arm depending on the molecular subtypes thats identified.

One of them has a PARC inhibitor, and one of them is monotherapy, depending on the arm.

Yeah, depending on the molecular subtype that's identified.

And they're all in parallel. Correct.

Theyre almost unparalleled unparallel correct, yes.

So you're expecting a handful of patients from each of the different arms of the study?

So youre expecting a handful of patients for each of the different.

Arms of the study.

Well, so one of the arms, which is monotherapy, is the MSI, so the microsatellite and stable.

So one of the arms, which is monotherapy is the MSI. So the microsatellite stable. So that's going to be pretty rare. So I don't know how many patients will get them there, but some of the ones that are more easier to enroll in the biomarker negative group, but sort of the ones that don't fit into the other guidance should enroll a little bit more aggressively so it depends on the arm and how rare it is.

So that's going to be pretty rare.

So I don't know how many patients we'll get in there, but some of the ones that are more easier to enroll in, like the biomarker negative group, it's sort of the ones that don't fit into the other categories should enroll a little bit more aggressively.

So it depends on the arm and how rare it is.

Okay, understood.

Okay.

Understood. Thank you.

Your next question comes from the line of Charles Zhou from Guggenheim Securities.

Thank you.

Understood.

Your line is now open.

Our next question comes from the line of Charles Zhu from Guggenheimer Securities.

Thanks for taking the questions.

Good afternoon, everyone and thanks for taking my questions first one as a follow up to one of the earlier questions that was asked perhaps.

Your line, is now open.

Thank you.

Good afternoon, everyone, and thanks for taking.., my questions.

Your next question comes from the line of Mara Goldstein from Mizzou.

With respect to terminating by specific checkpoint inhibitors due to uncompetitive early clinical data have your internal benchmarks for these kinds of go no go decisions remained constant as you've brought these bi specific checkpoints.

First one as a follow-up to one of the earlier questions that was asked perhaps.

With respect to terminating bispecific checkpoint inhibitors due to, you know, uncompetitive early clinical data, have your internal benchmarks for these kinds of go, no-go decisions remained constant, you know, as you've brought these bispecific checkpoints, you know, through early-stage studies?

<unk> early stage studies and by extension should we expect that the <unk> 104 dose escalation data dataset coming up could be comparable to the sort of readout. We saw from let's say the initial <unk> data. Thanks.

And by extension, should we expect that the XMAD-104 dose escalation data set coming up could be comparable to the sort of readout we saw from, let's say, the initial VoodalaMap data?

Thanks.

So have our metrics remain the same in the sense that we're always looking at how the competitive landscape is changing so that that concept is constant but it is a competitive landscape gets more difficult and as the bar rises our bar for for data is going to rise. We also look at what indications you might be in and.

So have our metrics remained the same?

Well, in the sense that we're always looking at, how the competitive landscape is changing, so that concept is constant, but as the competitive landscape gets more difficult and as the bar rises, our bar for data is going to rise.

We also look at what indications you might be in and how the drug is going to be used. Recall that XMAD-841, CTLA-4-LAG-3 bispecific, was intended for use in combination with Pembro, or Nevo.

How the drug is going to be used recall that.

<unk> X Nab <unk>, particularly for lag three by specific was intended for use in combination with Pembroke.

It's intended to be used for combination with PD-1, and so you're always positioning it as a combo agent, and so it has a different set of comparators, right?

<unk> intends to use for companies with PD, one and so youre always positioning it as a combo agent and so it has a different set of competitors right you'd be comparing that to <unk>.

You'd be comparing that to Nevo-Ipi, to Nevo-Relatlamab, to Pembro-Chemo, as opposed to a monotherapy or a PD-1 containing agent like, say, our XMAD-104.

<unk> Mab to Pembroke chemo.

As opposed to a monotherapy or a PD one containing agent like say <unk> 104, I would say that we have not had expansion cohorts accrue enough to show data at <unk> for <unk> 104. So it is going to have just the escalation portion and I recall.

I would say that we have not had expansion cohorts accrue enough to show data at ASCO for XMAD-104, so it's going to have just the escalation portion, and I recall at our – actually, no, I take it back.

At our accident and I take it back our first data look at it.

Our first data look at XMAD-717 was just escalation with very little expansion, so it's going to look similar to that, maybe just a smidge less.

<unk> seven <unk> seven was just escalation with that with very little expansion. So it's going to look similar to that maybe just a smidge less.

Got it.

Got it in terms of in terms of the number of patients.

Doses and so therefore, how much youll be able to glean from it.

Sounds good.

Got it great. Thanks that makes sense.

Maybe just one quick follow up so regarding <unk> and.

In terms of the number of patients, the doses, and so therefore how much you'll be able, to glean from it.

In prostate cancer and as a follow up to another previous question. So it sounds like you will have an early look across multiple cohorts, but the study itself will obviously continue to accrue patients and data beyond the near term to disclosure. Perhaps can you also provide a little bit more color around your thinking around how much patient data.

Generally need to accumulate before making potential go no go decisions for Red Registrational studies in prostate cancer.

The go no go.

Well I think.

<unk> on how good the data is and what the subgroup is so remember like if you look at what <unk> did in there I think it's the cosmic <unk>. One study they had a couple of hundred patients of data right, but theyre looking at it as a big group for their Cabo combination with the <unk>.

I think for us.

We're sort of breaking it down into sort of molecular subgroups. So there's aggressive variance there as a biomarker negative theres PARP.

<unk>.

Sort of PARP responsive and MSI unstable. So if we go for subgroup, we could probably use a lot less data, but if we go for a larger study going across all castrate resistant prostate cancer will probably need more data to be confident defined and note. We define each of the subgroups based on what we thought the rarity of the tumor was and the <unk>.

<unk> entered the aggressive subtypes or 20 patients per arm within this phase III.

<unk> subtype, and we think that would be adequate to make a go no go.

Got it.

Got it great. Thanks for taking my questions.

Your next question comes from the line of Ed <unk> from BMO capital markets. Your line is now open.

Your line is now open.

Great.

Hi.

Great. Thanks for taking the question. So I have another one on <unk> 104.

Thanks.

This is Tupouat from Mara Goldstein.

That makes sense.

I have a question on the cytokine program.

And maybe just one quick follow-up.

Sort of the.

Early plans for expansion if you could speak to any tumor types that look interesting at this point or could potentially be explored and then I guess secondly, we're going to see some data from.

So regarding, Vudalumab and prostate cancer, as a follow-up to another previous question, so it sounds like you will have an early look across multiple cohorts, but the study itself will obviously continue to accrue patients and data beyond the near-term disclosure.

You know, perhaps can you also provide, you know, a little bit more color around your thinking around how much patient data do you generally need to accumulate before making, you know, potential go-no-go decisions for registrational studies in prostate cancer?

From other PD, one <unk> four agent that as growing.

How we should think about any molecular differentiation or any potential read throughs from a mechanistic standpoint that you would be looking to add these datasets. Thank you.

Thanks.

So just to be clear you had one question about ex map 104 tumor types that we might or might not be interested in the other one about <unk>.

For go-no-go?

Molecular differentiation of our PD, one <unk> 700, <unk> is that right.

Well, I think it depends on how good the data is and what the subgroup, is.

So remember, like, if you look at what Exelixis did in their – I think it's the COSMIC-21 study, you know, they had a couple hundred patients of data, right, but they're, looking at it as a big group for their CABO combination with the TISO.

I think for us, you know, we're sort of breaking it down into sort of molecular subgroups.

That's correct.

Okay, great on the <unk>.

So there's aggressive variants, there's biomarker negative, there's sort of PARP-responsive, and MSI-unstable.

So if we go for a subgroup, we could probably use a lot less data, but if we go for a larger, study going across all, you know, castrate-resistant prostate cancer, we'll probably need more data to be confident and define the response.

We really can't comment on the tumor types until after we show our.

After we show our data at <unk> and there'll be there'll be information there that will make it clear what tumor types. We're going after another expansion of course, we will define it the expansion cohorts will be listed in our presentation with rationale. So so that's coming.

And no, we define each of these subgroups based on what we thought the rarity of the tumor was, and the ones that are the aggressive subtypes are 20 patients per arm within this phase two for each subtype, and we think that would be adequate to make a go-no-go.

Your next question comes from the line of Etzer Darout from BMO Capital Markets.

Your line is now open.

As the other one in molecular differentiation for other PD one's equally for us at <unk>.

Our molecule is I think only one other molecule that we're aware of has a similar design which is this.

This designed to create a molecule that really needs both both targets on the T cell to engage right rather than most of the designs, where you have got a bivalent binding to both PD, one and <unk> four so youre going to have high affinity binding each ours are relatively low activity. If you only have a PD one positive cell and very little activity.

The <unk> four positive only sell but good activity with both the only other program. We're aware of is Astrazeneca, which just released some initial data we recall at ACR.

So that molecular differentiations, we think at the root of our potentially differentiated safety profile.

And so I think that's how we view our real competition.

Question around 707 or 100.

Okay Sir.

That's how we view our real competition because again, how are you going to combine with potentially really toxic chemo regimens like we're exploring in the <unk> phase III I think that's the way we're going to be able to use this kind of agent competitively.

Great.

Great. Thank you.

Your next question comes from the line of Gregory <unk> from RBC capital markets your lifestyle brand.

Basically, I'm curious to hear your thought on the cis-targeting approach for cytokine, therapeutics.

Thanks for taking the question.

Hi, This is <unk> on for Greg. Thank you for taking our questions and congrats on the progress maybe first just a follow up question on one of four could you just expand a little bit on your earlier mention of that historical challenges Iqos program, where do you think potentially you show differentiation.

So I have another one on XMAB 104.

Now, you just showed the data on LAC3, IL-15 bispecific at the ACR, and, you know, whether, you have enough evidence to say that this approach is potentially safer and more effective and could be incorporated into your clinical program, you know, in the near future?

I guess, you know, sort of the early plans here for expansion.

Thank you.

If you could speak to any tumor types that look interesting at this point or could potentially be explored.

Thanks.

I'll touch on the – how we're thinking about it from a development pipeline standpoint.

Sure. So hey, John did you want to handle that one or should we go forward here.

Within our – what we call, you know, our early – our early development considerations, were advancing a number of the activities we would need, and we've not yet publicly guided on expectations for timing of that being in the clinic.

Yes, I think I'll leave that question repeated though im sorry.

And then, I guess, secondly, you know, we're going to see some data from other PD-1 CTLA-4 agents at ASCO, and maybe how we should think about, you know, any molecular differentiation or any potential read-throughs from a mechanistic standpoint that you would be looking to at these data sets.

You know, as to the scientific rationale, I think it's fantastically strong, and John, can go over that in a second, but really, until you're in the clinic with these brand, – completely brand-new MOAs, you really don't know much.

Yes, sure just wondering if he could expand a little bit on a historical challenges of iqos targeting programs.

Barclays show differentiation.

Thank you.

Yeah.

Oh, yes, yes.

Basically I mean, Bob alluded to this earlier right. So this is.

We know all the historical challenges the iqos programs in this molecule with kind of magical when we when we put these two different price together. This came out of an empirical screen of combining various PD one with various other co stimulatory target.

So, Etzer, just to be clear, you had one question about XMAB 104 tumor types that we might or might not be interested in.

Yeah, and, you know, I'll add to that, yeah, on the cis-targeting, you know, the basic, idea is we started with an IL-15 like XMAP306, which is, you know, vastly potency reduced, and then when we format into that – that arm into a single-chain IL-15 RL fusion, and then target it with LAC3, it's a little bit further reduced, and so, basically, when we use that cis-avidity effect, the LAC3 targeting on those – the LAC3-positive T-cells effectively restricts its activity only to that LAC3-positive T-cell population, and the hypothesis, which is supported by all kinds of literature, including, you know, very recent papers from Steve Rosenberg's lab, is that LAC3 is a very good marker of neoantigen-reactive CD8-positive T-cells, and so, if we could just selectively zero in on that particular population, that really could potentially open up a very strong therapeutic index for athletics.

If you may just sneak one in on the 306 combination, any additional color you could provide on, that front in terms of indications or potential combination partners, any chance that you would explore a combination with NK or T-cell therapy, thank you.

So just recall that molecule, XMAT306, our engineered potency out of 15 is in a co-development, collaboration with Genentech, it's a 55-45 worldwide split, and both companies have the right to initiate studies.

We plan on initiating studies and we're in the stage of sort of really ramping one up, right now to get going, we'll disclose details about that later, but I think both T-cell and NK-cell mechanisms are important to explore in both.

And then all of our preclinical in vitro assays.

<unk> four was the strongest in terms of activation of T cells that included an in vitro as well as.

R&D Evo mouse studies, where we just saw raging hot activity on the T cells. So.

The other one about molecular differentiation of our PD-1 CTLA-4, which is XMAB 717 or Brudalidab.

We fully expect Genentech to expand beyond what they're already doing with the teslizumab, combos and now DARA combos, and you'll hear more from Xencor.

Is that right?

First we don't completely understand why this thing is.

That's correct.

I think there's a great potential for these exogenous IL-15 and exogenous cytokine approaches, to cell therapy scientifically, I just don't think we can talk about any kind of concrete plans yet.

Got it.

Thank you so much.

Different but it was intriguing enough that we thought it was worth pursuing clinically so.

It's a different beast than those other iqos combination, yes, so it's a very different beast and that also encourage us that perhaps the central problem that the other the iqos targeting.

Normal mono mono specific bivalent antibodies have what's toxicity right they seem to be pretty toxic and they were hard to use the vastly different profile. We have with our molecule. For example, it has no effector function in the FC So we wouldn't expect it to deplete iqos positive cells.

We are hopeful that that allows us to have a differentiated profile that maybe maybe toxicity limited the efficacy because they couldnt get to enough dose perhaps.

The historical molecules, so very different design, hopefully can overcome that toxicity limitation and see the activity there.

That's what we're that's what the rationale was for the program.

Okay, great.

On the XMAB 104, we really can't comment on the tumor types until after we show our data at ASCO. And there'll be information there that'll make it clear what tumor types we're going after in our expansion cohorts.

Great. Thank you and then maybe just another one on modem ad.

When do you expect to see some initial data from the triplet study and also on the mono therapy just wondering if.

If we could hear a little bit about your latest thinking around opportunity there and path forward.

Lastly, just on the sub Q formulation.

How that will be phased into the expansion study.

We will define it.

Yeah, we're not guiding on our first data from the.

Triplet <unk> Lenalidomide study. It just started we'll guide on expectations for first data later note that it is a.

Yes.

Safety run in at two doses followed by ultimately the randomized stage. If we go forward. So we will have some interim data, but we'll guide on timing for that at another point.

What I would comment on how we're going to phase in the sub Q and what the monotherapy the rationale for continuing the expansion, yes. So a couple of things. So the first thing about the landscape. We are following that very closely and I think one of the things is that car T is definitely moving into second line right.

Yeah, the expansion cohorts will be listed in our presentation.

The data is very strong there.

With rationale.

So, that's coming.

So the landscape is changing and one of the things I want to point out is that the what is considered relapsed refractory diffuse large b cell lymphoma has changed and so what we're noticing in our studies as we're seeing a lot of car T refractory patients coming into our studies.

As to the other one, molecular differentiation for other PD-1 CTLA-4s at ASCO, our molecule is, I think, one other molecule that we're aware of has a similar design, which is this design to create a molecule that really needs both targets on the T cell to engage, right, rather than most of the designs where you've got a bivalent binding to both PD-1 and CTLA-4, so you're going to have high-avidity binding to each.

Ours are relatively low activity if you only have a PD-1 positive cell, and very little activity with a CTLA-4 positive only cell, but good activity with both.

The only other program we're aware of is AstraZeneca's, which just released some initial data.

We recall it AACR.

So, that molecular differentiation is, we think, at the root of our potentially differentiated safety profile, and so I think that's how we view our real competition.

Especially in the diffuse large b cell lymphoma group, but we're still encouraged by our data. So in terms of sub Q I think everybody suspects that.

Was the question around 717 or 104?

717 was the second one.

Okay, sure.

That's how we view our real competition because, again, how are you going to combine with potentially really toxic chemoregimens, like we're exploring in the DALMAB Phase II?

I think that's the way we're going to be able to use this kind of agent competitively.

Using our Q will sort of change the therapeutic index offer a better safety profile allow you to escalate faster and even higher in dose and so as we introduce the Q later this year, we're going to see how good. It is and then make decisions on our current studies, which are currently IV.

Do we convert them over to sub Q, but again I think we need to see the early data first but I think everyone is encouraged with that.

In terms of our monotherapy data.

Planning to release additional monotherapy data from our I view IV study in our phase one that's in diffuse large b cell lymphoma, and Follicular lymphoma.

This will be IV.

I think that data again looks good.

Could the study's design in which way the data quality is good enough for registration, but would it be worth it since other companies are probably going to file.

Ivy sort of single arm data in the near future. We don't think monotherapy ultimately is the long term.

The long term player even frankly, the medium term play.

In <unk> III is trying to get into the B lymphoma landscape monotherapy data simply I think not going to compete against the myriad of combinations that are proceeding some of which have already shown glimmers of good activity from from early early studies, whether it's chemo combos, we're very excited by our chemo free regimen.

So the monotherapy opportunity as much as anything is.

This study does not about thinking that theres, a great opportunity, there, but more about establishing that baseline of data.

And bringing forward enough data to make sure we can.

Demonstrates the rationale for our further studies exactly right now.

That's very helpful. Thank you very much.

Your next question comes from the line of <unk> Zhou.

Your next question comes from the line of Dane Leon from Raymond James.

<unk> Vernon.

Line is now open.

Great.

Your line is open.

Great. Thanks, very much for taking my question.

Two from me first on the discontinuation.

Paul.

Do the math I guess the <unk> target.

Endocrine tumors and you show some activity back.

The reason for this to continue.

Particularly the indication.

Do you have anything to do with the commercial opportunity.

Because you learn something in Palm city.

Thank you Jamie.

And second question a quick one.

On to R&D might be.

Should we.

Thanks very much.

So on the <unk> due to map.

Stop in neuroendocrine tumors are net I think it was as much as anything not so much the commercial opportunity per se, but rather the very very long clinical trials, you would have to do to achieve them where.

Historically in nets.

<unk> would face that as well here in their long PFS and OS studies that are long to accrue and very long time and points out past two years in many cases, so we looked at the timeline for how that might go and it didn't seem like something that made sense and even an NES. There is a shifting landscape so that was it.

To really be well set up to start our multiple ascending dose trial, which we're currently in preparation for and we'll also start this year and we'll give the details about that later.

Great.

Quick follow up.

The.

Should you have a vaginal.

Since you mentioned sort of loan duration.

Duration are you thinking maybe potentially out licensing. These two programs that you did for some others.

Thanks very much.

We're always open to finding ways for molecules, we make the potential to benefit patients and accrue value to the company.

So I would say everything's on the table I'm not going to guide to that I would say, it's not a high priority for us for these two programs to find partnerships, where I think we've got other fish to fry, but never say never.

No, thank you.

Hi.

Great. That's helpful. Thank you.

And our next question comes from the line of Peter Lawson from Barclays. Your line is now open.

Your next question comes from the line of Gregory Renza from RBC Capital Markets.

Thank you and congrats on all the progress.

This is Jon on for Peter Thanks for taking the question just to follow up a little bit more on the discontinuation for your <unk> four.

Your line is now open.

Luxury so anything in that phase one data that you have developed so far that pointed to you would be more negative on the approach of <unk> four lag three or do you think it was just more based on the molecule you had and what you want to revisit making another cta for luxury and then just also a little bit on the demand.

Maybe I will use my question and focus on the expected initial data on Ludelumab in, the back part of the year.

Just in light of discontinuation what is it that you're actually looking from that second half data that would.

Point to you that you want to go forward and then further do.

Do you think that this will be substantial enough update in second half for you to make that decision.

First of all the <unk>, it's not going to be enough data for the go no go it's going to be an initial look at safety and whatever efficacy. We can see from that a few handfuls of patients.

Across these different molecular subtypes.

Tolerability in combination with aggressive chemo.

I think a very important thing.

And to look at it as really shows the potential but we don't anticipate efficacy go no go at in this year's update will have been less than one year into <unk>.

Study start.

So, we saw interesting data in MCR-PC, I think, last year, if my memory serves me correctly, and, you know, it seems like you guys established the premise that for what had been previously tested with, I think, PD-1 and CTLA-4 in a similar patient population, you're achieving similar results, albeit maybe with less toxicity.

What are you going to be looking for from this initial data from the Phase 2 study, and then how specific you can get in terms of, like, the scale and scope of that data set?

I think it would be helpful to set expectations.

Hi, this is Yinglong for Greg.

Thank you.

And our next question comes from Brian up David Dye problem Smb's. Your line is now open.

Thank you for taking our questions and congrats on the progress.

Yeah.

Maybe first just a follow-up question on 104.

Before I pass this to Alan, I'll say, recall, we started this study just very late last, year.

Great. Thanks for taking my questions. So one question on medallion that we saw in the data that there were some modest level of equivalent to a rash and pruritus around 31% to 46%, but could you share with us the physician feedback on the Tolerability profile, especially in the context of the combination and the various different.

Could you just expand a little bit on your earlier mention of that historical challenges of ICOS programs, where you think 104 could potentially show differentiation?

So, by data cutoff for second half, and it was last year, we had the MCR-PC data.

Sure.

So, hey, John, did you want to handle that one, or should we go for it here?

Yeah, I think I need that question repeated, though.

Prostate cancers.

I'm sorry.

So.

Just to make sure we heard your question right you were commenting that.

The most common AE, we presented at <unk> last.

Last year <unk> was rash at around 30% and you're wondering how that might.

What might happen with chemo in terms of synergistic Tox is that what youre asking that's correct, yes, that's correct.

Would you expect to see us through a higher.

No tolerability or safety issues, when you combine with <unk>.

Typically companies yes.

By data cutoff, we should probably have about, I don't know, seven or eight months of accrual, and so it'll be on the order of a few handfuls of patients that we can show, and I think really key here is, like you alluded to, that safety-efficacy balance, because, recall, this study is in combo with chemo and potentially PARPs based on molecular subtypes, so can we start building on this as a backbone?

So yes, let me just sort of generally talk about the Tolerability of 707, which we are very impressed with I mean remember when you give a PD one <unk> four combination with the two drugs independent like Nemo and AP.

Yeah, Basil, not much to add.

I'll just say that, you know, a lot of our work is sort, of based on previous work from Pembro and Nevo.

A third of patients develop colitis and have to discontinue so much showed that.

You know, I think the early data showed that there was a benefit in combining PD-1 with CTLA-4, but it's challenging to do that.

Usually just give the Nemo and then they give the IP for a short period of time four courses I think is the latest thinking.

Right now so when we looked at our data from <unk>, we had a gi diarrhea rate of around 10%, which was very tolerable much lower and rash was the most common AE.

And so we were encouraged by our early data, you know, in our phase one, which we reported, at CITSE, where we have a moderate response rate, even though it was a small number of But moving forward, you know, I think the tolerability allowed us to sort of design, a really novel study where we look at different molecular subgroups and then combine with the standard of care, right?

For oncology patients rash is not a huge.

It's not a important toxicity, it's not going to cause you to discontinue now whether you would expect to see synergy with chemotherapy.

For that toxicity profile, probably not I mean, it's still early but if you think about it rashes are often treated with low doses of methotrexate, depending on the type of rash. So.

Yes for autoimmune diseases and so forth.

<unk> and so that's the old base. So I don't think we will see synergy in terms of toxicity, but we don't know its still early.

I think that was your question right David.

That's right. Thanks, so much for the for the answer and then another question on one of those or maybe just help me understand your biomarker strategy is to identify the responding tumor types for the program.

I think our strategy for identifying the responding tumor types is really about response.

Resist response, I think we have to be stringent about that.

Obviously characterized biomarkers because understanding the mechanism hope you glean insights into dose selection. The rationale for maybe if you see some kind of activity or toxicity in certain patients, but no. It's about it's about.

The kind of tumor response, you see not really the biomarkers.

Got it thank you so much.

Your next question comes from the line of maybe nearing Martin from Wedbush Securities. Your line is now open.

Yeah, sure.

I'm just wondering if you could, you know, expand a little bit on the historical challenges of ICOS targeting programs, where you think 104 could show differentiation?

Oh, yeah.

Yeah, being able to go on top of chemo would, I think, be a big edge here relative to the, limitations you might have faced otherwise.

Thanks for taking the question and then switch to <unk> for a second.

Speaking of component of profiles.

It's a pretty competitive space.

What do you think you need to hit with the Triple combination in terms of.

Our response rate.

Consider.

Advancing the program further.

Yes, I think that it is.

Still really hard to say for most of the studies because I think there is only one study we've seen a significant number reported it was just top line from the recent abbvie release, where they had about a 60% or in a 40% CR rate for that that are relapsed refractory <unk> population.

I think that sort of sets the minimum bar honestly for us because it is a similar population and so how much you can go from there we know that compensate about lenalidomide starts with about a 40% CR.

Our rate and about a 60% or.

Yeah, Yeah, and I think Theres a couple of things. So the L. Mind study is probably a good benchmark of what wed expect to see with just half and led by itself granted the landscape is changing a little bit but what's nice is remember we will have this run in so if we think the study may be underpowered, we can adjust the size of our changed strategy in the second part of.

The study.

Maybe a quick follow up.

Yes.

Not to.

Give too many hypotheticals, but.

Sure.

Pushing those patients to see are more important to you or is it kind of generally the overall response rate.

More important for you when you assess the prospects.

Yes, it's a good question I think thats more of a qualitative answer I think CR is always important right. So I think youll get responses, but when you look at the competitive landscape I think the power of the car T has been that <unk> been able to push patients into CR that are durable right and the question is can buy specifics do something similar to that.

Alright, and Thats, why we think that.

The potential for additive or maybe synergistic activity with a CD 19 targeting NK cell recruiting high DTC antibody is something that just adds another avenue that avoids the toxic chemo that maybe lets us move that needle.

Okay.

Got it.

Thanks.

Thank you there are no further questions at this time I would like to turn the call over back to <unk>.

Thanks, very much for joining us today, everybody and we look forward to updating you again in the near future.

Bye bye.

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

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Yeah, no, that's basically, I mean, Beth alluded to this earlier, right?

And so it should be, you know, with a few handfuls of patients to get a read, start to get a handle on safety, see if there's any acute issues that arise.

Good afternoon, ladies and gentlemen, and thank you for standing by and welcome to the <unk> first quarter 2022 conference calls.

And of course, we'll show whatever efficacy data we have by that point.

This time all parties spots are in a listen only mode.

So I think it'll be a solid but pretty early look.

After the speaker's presentation, there will be a question and answer session. Please be advised that this call is being recorded.

Companies to quest.

So, this is, you know, we know all the historical challenges of the ICOS programs, and this molecule was kind of magical when we, you know, when we put these two different sites together.

And note, we are committed to prostate cancer.

Now I would like the third the kilometer speaker today.

Charged lives head of corporate Communications and Investor Relations. Please go ahead.

Thank you and good afternoon earlier today, we issued a press release, which outlines the topics we plan to discuss today.

This came out of an empirical screen of combining various, you know, PD-1 with various other co-stimulatory targets, and then all of our preclinical in vitro assays, the 104 was just the strongest in terms of activation of T cells, you know, that included in vitro as well as, you know, our vivo mouse studies, where we just saw, you know, raging hot activity on the T cells.

We're starting our second study, which is monotherapy in a clinically defined high-risk population as well, along with some gynecologic tumors in a different basket in that same phase, too.

This release is available at Www Dot <unk> Dot com with me on the call are baffled that he is president and Chief Executive Officer, Allen Yang Chief Medical Officer, John Kush, Chief Financial Officer, and John <unk>, Chief Scientific Officer will join US when we open up the call for your questions. After prepared remarks before we begin I would like to remind you that during the course of this conference call is then.

So, I'll confess, we don't completely understand why this thing is different, but it was intriguing enough that we thought it was worth pursuing clinically.

So, it's a different beast than those other ICOS combinations.

<unk> management may make forward looking statements, including statements regarding the company's future financial and operating results future market conditions, the 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.

Yes. Some of the 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 recently filed annual report on Form 10-K, and quarterly report on Form 10-Q.

Yeah, and just to add a little bit more color on that, remember the BMS program, when they, looked at the Checkmate, I believe it was the 6-5-0 study in combination of NEVO and IPPE, the combo was better.

With that let me pass the call over to Basil Thanks, Charles and good afternoon, everyone continuing with the approach we took last quarter, we're going to make a few brief comments before spending the majority of today's call or questions.

Yes, it's a very different beast, and that also encouraged us that perhaps the central problem that the other ICOS, that the ICOS targeting, you know, normal monospecific bivalent antibodies have was toxicity, right?

But in terms of their registration phase 3, they're going, with NEVO plus chemotherapy, just dosotaxel as a single agent without the IPPE.

They seem to be pretty toxic, and they were hard to use.

So it sort of speaks to the challenges of combining PD-1 with C-TILA-4.

So.

As I like to usually open when we used our array of modular approach to engineering tools to create a broad internal development portfolio in oncology and autoimmune diseases, which allows us to take multiple simultaneous shots on goal in the clinic. Our intent remains to use proof of concept data from these early stage studies.

Which programs, we advance, which we terminate in which we partner so that we're most efficiently using our cash and our employees.

And that's what we're looking at.

In a moment alan's going to review, our advancing clinical programs and upcoming plans, but first today, we announced our plan to terminate internal development of two phase one programs <unk> and <unk>, which focuses our resources on those clinical programs of ours with the greatest potential for success and makes room in our portfolio for the next wave of <unk> bi specifics.

Maybe we can do it better.

Sorry, can I just clarify one thing with you guys?

Are all three arms of the study, monotherapy, plus PARP plus chemo, are those...

<unk> cytokines.

No, no.

<unk>, our <unk> by CD, three by specific antibody and extending for one or <unk> four by lag three bispecific antibody. After reviewing the data generated to date, we believe that neither program has competitive enough clinical profile in their respective areas, particularly when compared to the programs. We are currently advancing.

Are they all in parallel?

So we're going to keep supporting patients currently enrolled in the study, including by continuing to provide study drug.

The vastly different profile we have with our molecule, for example, it has no effect or function in the FC, so we wouldn't expect it to deplete ICOS-positive cells.

So we'll have...

Now a core piece of our strategy is leveraging our plug and play ask Matt FC domain through licensing transactions, especially in therapeutic areas outside of our core focus on oncology and autoimmune disease. We wanted to highlight the recent FDA approval for Lexi on Astrazeneca Ultra mirrors for adult patients with generalized myasthenia gravis its third approval in the U S.

We are hopeful that that allows us to have a differentiated profile that maybe toxicity limited the efficacy, because they couldn't get to enough dose, perhaps, of the historical molecule.

So, very different design, hopefully can overcome that toxicity limitation and see the activity there.

Well <unk> of course incorporates our extend FC domain for longer half life. We also bolstered our cash position with over $70 million in royalty revenue this quarter for the Covid antibodies petroleum that which incorporates the same extend FC domain.

From our partners Vir and GSK.

Because of the rapidly shifting COVID-19 variance to keep emerging we expect this revenue to drop very substantially next quarter and beyond.

Now looking at our partnerships for the X mapped by specific FC domain and our T cell engagement tool kit last quarter, we highlighted encouraging early clinical data from Amgen's AMG 509 program in prostate cancer.

In addition to being an ex nabbed by specific uses the X men two plus one multivalent format for T cell engagement.

Now within the past quarter Astellas is asps to 138, and ex snap cloud and $18 two by CD three by specific antibody has advanced into clinical development for patients with gastric gastroesophageal and pancreatic cancers and we look forward to following this program too.

That's what the rationale was for the program.

So I'm trying to remember how much we've disclosed on clinicaltrials.gov, but we'll have a Trials in Progress poster. And there's five arms.

Now I'm going to turn it over to Allen Yang Our Chief Medical Officer, who is going to briefly review, our clinical programs and upcoming plans.

Great, thank you.

I think three of them have chemo.

Thanks, Basel, so starting with our CD three bi specifics and promote them app. Our CD 20 by CD three by specific antibody that we are co developing with Janssen, we announced that the first patient has been dosed in a potentially registration, enabling phase III study, where it is being evaluated in combination with <unk> plus lenalidomide in patients.

And then maybe just another one on Clomodomab.

One of them has a PARP inhibitor, and one of them is monotherapy, depending on the arm.

Yeah, depending on the molecular subtype that's identified.

Then they're all in parallel.

With relapsed or refractory diffuse large b cell lymphoma note. We are conducting this particular study ourselves and our partners more focus and insight are providing top of Sytem app.

They're all in parallel.

Correct, yep.

So you're expecting a handful of patients from like each of the different arms of the, study?

He has two parts the first of which is the safety run in followed by a planned randomization between the triple combination of <unk> map lenalidomide with or without promote them up later this year, we plan to present data from the expansion cohorts in the ongoing phase one IV monotherapy study.

Once you expect to see some initial data from the triplet study and also on the monotherapy, just wondering if we could hear a little bit about your latest thinking around opportunity there and path forward, and, you know, lastly, just on the subcube formulation, how that will be phased into the expansion study.

Thanks.

Well, so one of the arms, which is monotherapy, is the MSI, so the microsatellite and stable.

We're not guiding on our first data from the triplet PLAMO, tapasitomab, lenalidomide study.

In addition, we also plan to introduce subcutaneous dosing into this study.

Two plus one format in preclinical studies, we have shown this format preferentially kills tumor cells with high target antigen expression relative to normal cells, which may be of particular benefit against solid tumors.

Moving onto our tumor microenvironment activator bi specifics, our most advanced <unk> with Allomap, which targets PD, one and <unk> four double positive lymphocytes. We are conducting two phase III studies, the first of which is enrolling patients with metastatic castrate resistant prostate cancer.

Gynecological malignancies, or clinically defined high risk metastatic castrate resistant prostate cancer and we're supporting additional signal seeking investigator sponsored studies as well.

One of the study at <unk> in a few weeks from now.

Moving onto our suite of reduced potency cytokines, all engineered with our Bispecific FC domain and incorporating extend technology at the recent ACR meeting we introduced two preclinical stage programs, a decoy resistant IL 18, and the lag three targeted IL 15, which is bias towards binding inactivating lag.

Three positive T cells that are more likely to be tumor associated.

Clinically our most advanced cytokines as X map III Asics, a reduced potency long acting IL 15 FC fusion protein that we are co developing with genentech.

<unk> hundred six targets NK and T cells for the treatment of patients with cancer and the ongoing phase one dose escalation, we observed high levels of sustained NK cell expansion and evidence of peripheral effector T cell proliferation, and we announced last fall and we announced this last fall just recently genentech initiated in.

<unk> phase one study to evaluate the combination with anti <unk> three antibody <unk> in patients with relapsed or refractory multiple myeloma.

We ourselves are planning additional studies with <unk> in combination with other therapeutic agents and look forward to providing updates.

In the near future next.

Next is our wholly owned at <unk> 56 for reduced potency IL two <unk> FC fusion cytokines, which we are developing an autoimmune disease, we're conducting a single ascending dose study.

Phase one in healthy volunteers and later this year, we will present, our initial data from this study in.

In parallel we plan to initiate a multiple ascending dose study in patients.

Our third cytokines to enter the clinic will be the IL 12 FC ex Mab 662 for which we anticipate filing an IND near year end.

Finally, one additional exciting program, we plan to advance into clinical development. This year is our first CD 28 by specific antibody <unk> 808, which targets the broadly expressed tumor antigen <unk> III. This new class of bi specific is engineered to provide traditional CD 28 co stimulation of T cells activating them.

Went down to tumor cells now with that I'll hand, the call over to John <unk>, Our CFO to review our financial results. Thank you Alan <unk> broad FC technologies and the multiple partnerships that we have entered continue to provide us with opportunities to generate cash flows and strengthen our balance sheet and allow us to invest in our pipeline is by Pacific.

It just started.

So that's going to be pretty rare.

We'll guide on expectations for first data later.

Note that it is a safety run-in at two doses, followed by, ultimately, the randomized phase if we go forward.

So, we will have some interim data, but we'll guide on timing for that at another point.

Antibody in engineered cytokines candidate.

In the first quarter, we received $83 $7 million of revenue from these partnerships.

Breakdown of the proceeds include $78 $7 million in royalties and $5 million and expected milestone payments, we'd like to point out that approximately $70 million of royalty revenue was from our <unk> partnership and it relates to sales of <unk> and given Gsk's recent comments about anticipated. So drove mid sales for the remainder of 2022.

We expect that future royalty revenue on net sales, so trove map will be substantially lower than first quarter amount.

As noted we continue to maintain a strong balance sheet as of March 31, our cash cash equivalents receivables and marketable securities totaled $683 6 million, which is an increase over December 31 amount of $664 1 million.

We currently estimate ending 2022 with between 500 $550 million in cash cash equivalents receivables and marketable debt securities.

Based on our current operating plans, we would expect to have cash to fund R&D programs and operations through the end of 2025.

You know, you want to comment on how we're going to phase in the subcube and what the monotherapy, the rationale for continuing in the expansion is?

I will refer you to our press release this afternoon, and our SEC filings for further review of our financial results.

With that we'd now like to open up the call for your questions.

Later.

Yeah.

So it depends on the arm and how rare it is.

Thank you at this time I would like to remind everyone in order to ask a question. Please press <unk>.

One.

Please press Star then the number one on your telephone keypad.

Our first question comes from the line of Jonathan Chang from <unk> Securities. Your line is now open.

So, a couple things.

Okay, understood.

Hi, guys. Thanks for taking my questions first question on X snap one O. Four can you help set investor expectations for the upcoming data at <unk>.

Sure I'll start with that thanks for the question on one of four it's going to cover our dose escalation portion of this study and the study is currently an expansion. So it is can we go to the dose escalation.

Of that agent where.

We're looking to see what kind of safe doses, we could achieve we know that there's been a history of iqos agents that have had challenges there.

So, the first thing about the landscape, you know, we are following that very closely, and I think one of the things is that CAR T is definitely moving into second line, right?

Thank you.

Yes, I'll open it and then I can let Alan jump in what we really are trying to do with our strategy that we've been executing now for several years has put a number of programs that have promising biology into phase one and uses data to judge which ones can have the characteristics that we could develop and potentially create a.

Our own drug with or partner in a way that we think is very valuable.

And so we're always looking at the efficacy versus.

Escape, which is always shifting and so this was done in the context of that and judging whether our resources could be better spent on other of our programs, who who's competitive profiles are more attractive so it's about safety and efficacy in the particular context.

The data is very strong there.

And so, the landscape is changing, and, you know, one of the things I want to point out is that what is considered relapsed refractory diffused large B-cell lymphoma has changed, and so what we're noticing in our studies is we're seeing a lot of CAR T refractory patients coming into our studies, especially in the diffused large B-cell lymphoma group, but we're still encouraged by our data.

I would say I'll pass it over to Alan now, but in general the efficacy bar for both of those settings is fairly high and that tended to be what drove our thinking.

So, in terms of sub-Q, you know, I think everybody suspects that, you know, using sub-Q will sort of change the therapeutic index, you know, offer a better safety profile, allow you to escalate faster, and even higher in dose.

And so, as we introduce sub-Q later this year, we're going to see how good it is and then make decisions on our current studies, which are currently IV.

Do we convert them over to sub-Q?

But, again, I think we need to see the early data first, but I think everyone is encouraged with that.

And in terms of our monotherapy data, you know, we're planning to release additional monotherapy data from our IV study in our Phase 1. That's in diffused large B-cell lymphoma and follicular lymphoma. This will be IV.

Yes, Jonathan I would like to say problem.

Probably the things to consider where actually outside the program. So if you look at <unk> 841 of dual lagged. The BMS slide three was approved it was a pretty involved the development program just for a relapsed refractor excuse me for melanoma and so when you look at ex map for one comparing it to our internal pipeline, we just thought we would.

B prioritize if there are better things to invest in our internal pipeline likewise for <unk>.

You know, I think that data, again, looks good.

The key thing that changes Amgen has AMG 757 in small cell lung cancer, which is showing good clinical activity and a good safety profile and then looking at our internal pipeline again, you just can't compare what we want to invest in so I think we decided to terminate that program as well.

The study is designed in which way the data quality is good enough for registration, but would it be worth it since other companies are probably going to file IV sort of single-arm data in the near future?

Yeah, we don't think monotherapy ultimately is the long-term play or even, frankly, the medium-term play in CD20, CD3s trying to get into the B-lymphoma landscape.

Note that there is investigator initiated studies that.

We expect for at least one if not both of those all will certainly support those with drug supply.

And see if patients can benefit and if good experiments in December from an internal investment perspective, it's really about where we get the most bang for the Buck.

Monotherapy data simply is, I think, not going to compete against the myriad of combinations that are proceeding, some of which have already shown glimmers of good activity from early studies, whether it's chemo combos.

We're very excited by our chemo-free regimen.

So the monotherapy opportunity, as much as anything, continuing the studies is not about thinking that there's a great opportunity there, but more about establishing that baseline of data and bringing forward enough data to make sure we can, you know, demonstrate the rationale for our further studies.

Understood makes sense and.

And just last question from me can you discuss the rationale for the X snap III zero six plus <unk> combination in multiple myeloma.

Exactly right.

Sure why don't we let.

John <unk>, our CSO take that one he is calling in remote Johnny there.

That's very helpful.

Thank you very much.

Your next question comes from the line of Zeke Dianxu from Varenburg.

Your line is open.

Yeah, Yeah, Yeah happy to take that yes, thanks, Jonathan.

Great.

Thanks very much for taking my question.

I think what it comes down to us.

Darko Lex.

It seems to have a pretty strong NK mediated activity against myeloma.

So two from me.

First, on the discontinuation, of Dibutamab, I guess the SSTR2 is the risk target in your endocrine tumors, and you show some activity there.

But there's another wrinkle in it.

Because there is.

Some small amount of <unk> 38 on the NK cells that actually takes a hit on the <unk> sales as well and so the hypothesis is that with our ability with 306 to massively expand the NK cells.

There might be additional synergy there on both fronts right just having more NK cells do job, but also being able to replenish.

Okay. So thats Agua takes out.

Understood. Thanks for taking the questions.

Thank you.

What was the reason for this discontinuity in that particular indication?

Your next question comes from the line of Charles Zhu from Guggenheimer Securities.

Thank you. Your next question Josh on the line of Mara Goldstein from Mizuho. Your line is now open.

Your line is open.

Good afternoon, everyone, and thanks for taking.., my questions.

First one as a follow-up to one of the earlier questions that was asked perhaps.

Does it have anything to do with the commercial opportunity, or is it really because you learned, something about the CDTs that engage your endocrine tumors?

Hi, Hi, this is <unk> from Mara Goldstein I have a question on the cytokine Proto.

My second question is a quick one.

Can you help us understand the IL-2, a program you, are developing, with that data there, and when should we be able to see the data?

Prototype program basically I'm curious to hear your thought on the fifth targeting approach my cytokine therapeutic now you did show good data on <unk>.

Thanks very much.

So on the Tidutamab stop in neuroendocrine tumors or NET, I think it was as much as anything, not so much the commercial opportunity per se, but rather the very, very long clinical trials you would have to do to achieve them, where historically in NETs, and I think Tidutamab would face that as well here, there are long PFS and OS studies that are long to accrue and very long time endpoints, out past two years in many cases.

With respect to terminating bispecific checkpoint inhibitors due to, you know, uncompetitive early, clinical data, have your internal benchmarks for these kinds of go, no-go decisions remained constant, you know, as you've brought these bispecific checkpoints, you know, through early stage studies, and by extension, should we expect that the XMAD-104 dose escalation data dataset coming up could be comparable to the sort of readout we saw from, let's say, the initial VoodalaMap data?

And whether you have enough evidence to say that is how would you potentially safer and more effective and it could be incorporated into a clinical program in the near future.

Thanks.

Thanks Al.

So we looked at the timeline for how that might go, and it didn't seem like something that made sense, and even in NET, there is a shifting landscape.

So have our metrics remained the same?

On the how we're thinking about it from a development pipeline standpoint. It is in our what we call. Our early our early development considerations were advancing a number of the activities. We would mean and we have not yet publicly guided on expectations for timing of that being in the clinic.

So that was really the driver for not wanting to pursue, NET, and then Alan mentioned for why the challenge in small cell lung cancer, potentially a great opportunity, didn't make sense anymore based on what we were seeing.

Well, in the sense that, we're always looking at how the competitive landscape is changing, so that concept is constant, but as the competitive landscape gets more difficult and as the bar rises, our bar for data is going to rise.

Could you repeat your question about IL-2?

I didn't catch that.

Yeah, just kind of, can you update us with the status right now, why should we be interested, in the data?

Oh, yeah.

We also look at what indications you might be in and how the drug is going to be used. Recall that XMAD-841, CTLA-4-LAG-3 bispecific was intended for use in combination with PEMBRO or NEVO.

It's intended to be used for combination with PD-1, and so you're always positioning it as a combo agent, and so it has a different set of comparators, right?

So the status of the study is we are currently in the Phase I single ascending, dose study in healthy volunteers, and we expect to have data from that study later this year that is essentially going to be your trifecta of safety tolerability, the biomarker data, you're looking for regulatory T cells to go up and for T effectors to not go up, really, and how long that lasts, right, the durability of it.

You'd be comparing that to NEVO-IPI, to NEVO-RELATLIMAB, to PEMBRO-CHEMO, as opposed to a monotherapy or a PD-1 containing agent like, say, our XMAD-104.

That trio of biomarker data, duration, and tolerability is going to tell us really how we stack up, I think, against that same sort of correlated, similar data that was released after SAD studies by some of the competition, and it will also allow us to really be well set up to start our multiple ascending dose trial, which we're currently in preparation for and will also start this year, and we'll give the details about that later.

Great.

Our first data look at XMAD-717 was just escalation with very little expansion, so it's going to look similar to that, maybe just a smidge less.

Just a quick follow-up on the genome of ASL.

Since you mentioned sort of long, trial duration, are you thinking maybe potentially of licensing these two programs, as you did for some others you discontinued?

Got it.

Thanks very much.

In terms of the number of patients, the doses, and so therefore how much you'll be able to glean from it.

Yes.

You know, we're always open to finding ways for molecules we make to potentially benefit, patients and, you know, accrue value to the company, so I would say everything's on the table.

Yes on the fifth targeting.

Got it.

The basic idea is we started with.

15, <unk> Nab three six which is <unk>.

Firstly the reduced.

And then when we format into that into that arm into a single train Alpha denaro confusion.

And then targeting lag three it's a little bit further reduced so basically when you we use that fifth avidity effect.

Our lag three targeting on the <unk> positive T cells effectively restrict this activity only to that lag three positive T cell population and the hypothesis, which is supported by all kinds of literature, including very recent papers from Steve Rosenberg's lab is that lag three is a very good <unk>.

Of Neo antigen reactive CDA positive T cells.

And so if we could just collectively zero in on that particular population.

That really could potentially open up a very strong therapeutic index for a cytokine.

Got it and if it made the sneak one in on a deal a big combination any additional color you could provide on backgrounds and indications are all potential com.

Combination partners any chance that you could you would explore combination with NK and T cell therapy. Thank you.

So just recall that molecule that 306 are.

Our engineered potency of <unk> is in a co development collaboration with Genentech.

It's a 50 545 worldwide split and both companies have the right to initiate studies, we plan on initiating studies in.

We're in the stage of sort of really ramping one up right now to get going and we'll disclose details about that later, but I think both T cell and NK cell mechanisms are important to explore them both.

We fully expect genentech to expand beyond what they're already doing with the Tesla lithium app combos, and now Dara combos and Youll hear more from EMCORE as for the cell therapies of course, that's an issue where we engineer <unk> have to have the basic meeting of the minds on what programs were are going to be advanced by.

By the two companies and so that's one where I think where we're going to have to guide on that later on specifics I think there's a great potential for these exogenous IL 15, and exogenous cytokine approaches with cell therapy.

Typically I just don't think we can talk about any kind of concrete plans yet.

Got it got it thank you very much.

I'm not going to guide to that.

Great.

Your next question comes from the line of Dane Leone from Raymond James Your line is now open.

I would say it's not a high priority for us, for these two programs, to find partnerships where I think we've got other fish to fry, but never say never.

Thanks.

Your next question comes from the line of Peter Lawson from Barclays, your line is open.

That makes sense, and maybe just one quick follow-up.

Alright, Thank you and congrats on all the progress.

This is Jiayuan for Peter.

Maybe I will use my question and focus on.

The expected.

Initial data on Allomap.

In the back part of the year. So we saw it we saw interesting data.

Yes.

See RPC I think last year, if my memory serves me correctly.

And.

It seemed like you guys establish the premise that for what had been previously tested with I think PD one <unk> four in a similar patient population, you're you're achieving similar results, albeit maybe with less toxicity.

Thanks for taking the question.

So, regarding VUDALIMAB in prostate cancer, and as a follow-up to another previous question, so it sounds like you will have an early look across multiple cohorts, but the study itself will obviously continue to accrue patients and data beyond the near-term disclosure.

What are you what are you going to be looking for from this initial.

Data from the phase two study.

And then a spin.

Specific you can get in terms of like the scale and scope.

Of that dataset I think it would be helpful to set expectations. Thank you.

Just to follow up a little bit more on the discontinuation for your CTLA-4 by LAG-3, is there anything in that phase one data that you had developed so far that pointed to you being more negative on the approach of a CTLA-4 LAG-3?

You know, perhaps can you also provide, you know, a little bit more color around your thinking around, how much patient data do you generally need to accumulate before making, you know, potential go-no-go decisions for registrational studies in prostate cancer?

Or do you think it was just more based on the molecule you had and what you want to revisit making another CTLA-4 LAG-3?

Before I pass this to Alan I'll say recall, we started the study.

Just very late last year, so by data cutoff for second half.

And then just also a little bit on the Voodoo Lab, just in light of the discontinuation, what is it that you're actually looking from that second half data that would point to you that you want to go forward?

It was last year city, we had the BMT RPC data by data cutoff, we should probably have about adding a seven or eight months.

And then further, do you think that this will be a substantial enough update in second half for you to make that decision?

First on the Voodoo Lab, it's not going to be enough data for the go-no-go.

Of accrual and so it'll be it'll be on the order of a few handfuls of patients that we can show and I think really key here is like you alluded to that safety efficacy balanced because recall. This study is in combo with chemo and potentially parks based on molecular subtypes. So can we start building on this as a base.

It's going to be an initial look at safety and whatever efficacy we can see from that few handfuls of patients across these different molecular subtypes.

Backbone.

Yes.

Much to add I would just say that a lot of our work is sort of based on previous work from Pembroke <unk> I think the early data showed that there was a benefit of combining PD, one with <unk> four but it's challenging to do that and so we're very encouraged by our early data in our phase one, which we reported 60, where we have a.

A moderate response rate, even though it was a small number of patients but moving forward.

The tolerability in combination with aggressive chemo is, I think, a very important thing to look at.

It really shows the potential.

I think the Tolerability allowed us to sort of design, a really novel study, where we look at different molecular subgroups and then combined with the standard of care right. So you will see that data with combination of 787 with aggressive chemotherapy or a PARP inhibitor or mono therapy in different subgroups and that will hopefully.

But we don't anticipate efficacy go-no-go in this year's update.

Bridge us to designing a registration enabling study, yes being able to go on top of chemo would I think be a big edge share relative to the limitations you might have faced otherwise and so it should be with.

With a few handfuls of patients to get a read start to get a handle on safety see if there's any acute issues that arise and of course will show whatever efficacy.

You can see we data we have by that point, so I think it'll be.

A solid but pretty early look and know we are committed to prostate cancer. We're starting our second study, which is monotherapy in a clinically defined high risk population as well.

Along with some gynecologic.

Tumors in a different different basket in that same phase II, yes.

Just to add a little bit more color on that remember the.

The BMS program when they looked at the Checkmate I believe it was the 6650 study in combination of vivo.

And it would be the combo was better but in terms of their registration phase III theyre going with Nemo plus chemotherapy, just docetaxel as a single agent without the AP. So it sort of speaks to the challenges of combining PD, one with <unk> four and Thats what were looking at maybe we can do it better.

Sorry can I just clarify one thing with you guys.

Are all three arms of the study in monotherapy, plus <unk>, plus chemo or those there's no not a parallel.

We'll have been less than one year since the study started.

So we'll have.

I'm trying to remember how much we've disc.

As disclosed on clinical trials, but we will have a trials in progress.

Poster if theres five arms I think three of them have chemo one of them has a PARP inhibitor and one of them is monotherapy, depending on the arm, yes, depending on the molecular subtypes thats identified.

Then there are almost all in parallel Unparallel correct, yes.

So youre expecting a handful of patients for each of the different.

Arms of the study.

So one of the arms, which is monotherapy is the MSI. So the microsatellite and stable. So that's going to be pretty rare. So I don't know how many patients will get them there, but some of the ones that are more easier to enroll in the biomarker negative group at sort of the ones that don't fit into the other guidance should enroll a little bit more aggressively so it depends on the arm and how rare it is.

Okay.

Understood. Thank you.

Okay.

Your next question comes from the line of Charles Zhou from Guggenheim Securities Your.

Thanks.

Your line is now open.

Good afternoon, everyone and thanks for taking my questions first one as a follow up to one of the earlier questions that was asked perhaps.

Obviously, safety data can give you a go-no-go at any time, whether you like it or not.

With respect to terminating by specific checkpoint inhibitors due to uncompetitive early clinical data have your internal benchmarks for these kinds of go no go decisions.

But we're optimistic that we can provide an update and fully expect to continue the trial after that update.

For go-no-go?

But it will give people a read on what is really the potential for this new way of targeting this pair of receptors.

<unk> constant as you've brought these by specific checkpoints.

Going back to the TLA-4 by LAG-3, is it the molecule or the target pair is essentially what you asked?

<unk> early stage studies and by extension should we expect that the <unk> 104 dose escalation data datasets coming up could be comparable to the sort of retail we saw from let's say the initial <unk> data.

I will say I don't know if anybody can address that, given that I think there's only one of these that's ever been in the clinic and it was ours.

I can say that we don't plan on going back and making another one, because as much as anything, I think the landscape of competition has moved and it's very different from what we all expected it to be three or four years ago, because you never know what it's going to be.

So we would not plan on making a new one.

But I don't think that reads on whether it's the target pair or the specific molecular design choices we made.

How the drug is going to be used recall that.

I wish I could answer that.

<unk> X Nab a four one particularly for lag three by specific was intended for use in combination with Pembroke.

<unk> intends to use for companies with PD, one and so youre always positioning it as a combo agent and so it has a different set of competitors right you'd be comparing that to <unk>.

<unk> <unk> to <unk>.

<unk> chemo as opposed to a mono therapy or a PD one containing agent like <unk> or <unk> 104, I would say that we have not had expansion cohorts accrue enough to show data at <unk> for <unk> 104, So it's going to have just the escalation portion.

And I recall at our actually now I take it back our first data look at at <unk> 107 was just escalation with that with very.

Little expansion. So it is going to look similar to that maybe just a smidge less.

Got it so in terms of.

In terms of the number of patients.

The doses and so therefore, how much you'll be able to glean from it.

Got it great. Thanks that makes sense.

Maybe just one quick follow up so regarding <unk> and prostate cancer and as a follow up to another previous question. So it sounds like you will have an early look across multiple cohorts, but the study itself will obviously continue to accrue patients and data beyond the near term to disclosure, perhaps can you also provide a little.

Bit more color around your thinking around how much patient data do you generally need to accumulate before making potential go no go decisions for Red Registrational studies in prostate cancer.

For go no go.

Well, I think it depends on how good the data is and what the subgroup is.

Well I think it depends on how good the data is and what the subgroup is so remember like if you look at what <unk> did in there I think it's the cosmic <unk>. One study they had a couple of hundred patients of data right, but theyre looking at it as a big group for their Cabo combination with the peso.

So, remember, like, if you look at what Exelixis did in their, I think it's the COSMIC-21 study, you know, they had a couple hundred patients of data, right, but they're looking at it as a big group for their CABO combination with the TISO.

I think for us, you know, we're sort of breaking it down into sort of molecular subgroups.

Sure.

I think for us.

So, there's aggressive variants, there's biomarker negative, there's sort of PARP-responsive and the MSI-unstable.

We're sort of breaking it down into sort of molecular subgroups. So there's aggressive variance there.

Mark or negative there's PARP.

Sort of PARP responsive in the MSI unstable. So if we go for a subgroup, we could probably use a lot less data, but if we go for a larger study going across all castrate.

So, if we go for a subgroup, we could probably use a lot less data, but if we go for a larger study going across all, you know, castrate-resistant prostate cancer, we'll probably need more data to be confident and define the response.

Mr. Prostate cancer will probably need more data to be confident defined and know we define each of the subgroups based on what we thought the rarity of the tumor was and the ones that are the aggressive subtypes or 20 patients per arm within this phase II free for each subtype and we think that would be adequate to make a go no go.

Great.

Your next question comes from the line of Etzer Darout from BMO Capital Markets.

Got it great. Thanks for taking my questions.

Your next question comes from the line of Ed Sara <unk> from BMO capital markets. Your line is now open.

Your line is now open.

Great.

Great. Thanks for taking the question. So I have another one on <unk> 104.

Thank you for taking the question.

Thanks for taking the question.

Congrats on the quarter.

So I have another one on XMAB 104, I guess, you know, sort of the early plans here for, expansion.

And sort of the.

Early plans for expansion if you could speak to any tumor types that look interesting at this point or could potentially be explored and then I guess secondly, we're going to see some data from.

If you could speak to any tumor types that look interesting at this point or could potentially, be explored.

And then, I guess, secondly, you know, we're going to see some data from other PD-1 CTLA-4, agents at ASCO and maybe how we should think about, you know, any molecular differentiation or any potential read-throughs from a mechanistic standpoint that you would be looking to at these datasets.

Some other PD, one <unk> four agents I'd ask on <unk>.

Maybe how we should think about any molecular differentiation or any potential read throughs from a mechanistic standpoint that you would be looking to add these datasets. Thank you.

Thank you.

So, Etzer, just to be clear, you had one question about XMAB 104 tumor types that we might or, might not be interested in.

So just to be clear you had one question about <unk> 104 tumor types that we might or might not be interested in the other one about molecular differentiation of our PD. One <unk> four <unk> 700, <unk> is that right.

The other one about molecular differentiation of our PD-1 CTLA-4, which is XMAB 717 or Voodalumab.

Is that right?

That's correct.

Okay, great.

Correct.

On the XMAB 104, we really can't comment on the tumor types until after we show our data, at ASCO.

Okay, great on the <unk>, we really can't comment on the tumor types until after we show our.

After we show our data at <unk> and there'll be there'll be information there that will that will make it clear what tumor types. We're going after another expansion of course, we will define it yes. The expansion cohorts will be listed in our presentation with rationale so so that's coming.

And there'll be information there that'll make it clear what tumor types we're going, after in our expansion cohorts.

We will define it.

Yeah, the expansion cohorts will be listed in our presentation.

With rationale.

So, that's coming.

As to the other one, molecular differentiation for other PD-1 CTLA-4s at ASCO, our molecule, is, I think, only other...one other molecule that we're aware of has a similar design, which is this design to create a molecule that really needs both targets on the T cell to engage, right, rather than most of the designs where you've got a bivalent binding to both PD-1 and CTLA-4, so you're going to have high-avidity binding to each, are relatively low activity if you only have a PD-1 positive cell, and very little activity with a CTLA-4 positive only cell, but good activity with both.

As the other one on molecular differentiation for other PD one <unk> four is at ESCO.

Our molecule is I think only one other molecule that we're aware of has a similar design which is this.

This designed to create a molecule that really needs both both targets on the T cell to engage.

Rather than most of the designs, where you have got a bivalent binding to both PD, one and <unk> four so youre going to have high affinity binding each are relatively low activity. If you only have a PD one positive cell and very little activity with a <unk> <unk> positive only sell but good activity with both the only other program. We are aware of is Astrazeneca, which just released them.

The only other program we're aware of is AstraZeneca's, which just released some initial, data, we recall, at AACR, so that molecular differentiation is, we think, at the root of our potentially differentiated safety profile, and so I think that's how we view our real competition.

Initial data we recall at ACR.

So that molecular differentiation is we think at the root of our potentially differentiated safety profile.

And so I think that's how we view our real competition was the question around 707 or 147.

Was the question around 7.1.7 or 1.0.4?

7.1.7.

Okay, sorry.

Okay Sir.

That's how we view our real competition, because, again, how are you going to combine with potentially, really toxic chemoregimens like we're exploring in the DALMAB Phase II?

That's how we view our real competition because again, how are you going to combine with potentially really toxic chemo regimens like we're exploring in the <unk> phase two I think that's the way we're going to be able to use this kind of agent competitively.

I think that's the way we're going to be able to use this kind of agent competitively.

Great.

No, thank you.

Great. Thank you.

Our next question comes from the line of David Leiper, SMBC.

Your next question comes from the line of Gregory Renza from RBC Capital Markets.

Your next question comes from the line of Gregory <unk> from RBC capital markets your lifestyle brand.

Your line is now open.

Great.

Hi, this is Yinglong for Greg.

Hi, This is Neil on for Greg. Thank you for taking our questions and congrats on the progress maybe first just a follow up question on one of four could you just expand a little bit on your earlier mention of that historical challenges Iqos program, where do you think went elsewhere potentially show differentiation.

Thanks for taking my questions.

Thank you for taking our questions, and congrats on the progress.

Maybe first just a follow-up question on 1.0.4.

Could you just expand a little bit on your earlier mention of that historical challenges, of ICOs programs where you think 1.0.4 could potentially show differentiation?

So one question on the DALY map.

Sure.

So, hey, John, did you want to handle that one, or should we go for it here?

Thanks.

Sure. So hey, John did you want to handle that one or should we go forward here.

Yeah, I think I need that question repeated, though.

I'm sorry.

Yes, I think I'll leave the question repeat it sorry.

So we saw in the CITSI data that there was some modest level of equivalent to rash and pruritus, around 31% to 46%.

Yeah, sure.

Yes sure.

Just wondering if you could expand a little bit on a historical challenges of Iqos targeting programs or you think one for Christian I'll differentiation.

Oh, yes, yes.

Basically I mean <unk> alluded to this earlier right. So this is.

We know all the historical challenges the iqos programs in this molecule with kind of magical when we when we put these two different price together for this came out of an empirical screen of combining various PD one with various other co stimulatory target and.

Just wondering if you could, you know, expand a little bit on the historical challenges of ICOS targeting programs, where you think 104 could show differentiation?

And then all of our preclinical in vitro assays. The Warner for was just the strongest in terms of activation of T cells that included an in vitro as well as you know.

Our vivo mouse studies, where we just saw raging hot activity on the T cells. So.

I'll confess we don't completely understand why this thing is different but it was intriguing enough that we thought it was worth pursuing clinically so.

A different beast than those other iqos combination, yes, so it's a very different beast and that also encourage us that perhaps the central problem that the other the iqos targeting <unk>.

Normal mono.

No specific bivalent antibodies have with toxicity right they seem to be pretty toxic and they were hard to use the vastly different profile. We have with our molecule. For example, it has no effector function in the FC So we wouldn't expect it to deplete iqos positive cells.

We are hopeful that that allows us to have a differentiated profile that maybe maybe toxicity limited the efficacy because they couldnt get to enough dose perhaps.

The historical molecules, so very different design, hopefully can overcome that toxicity limitation and see the activity there.

That's what we're that's what the rationale was for the program.

Great. Thank you and then maybe just another one on demand.

Oh, yeah.

Yeah, no, that's basically, I mean, Beth alluded to this earlier, right?

So, this is, you know, we know all the historical challenges of the ICOS programs, and this molecule was kind of magical when we, you know, when we put these two different sites together.

When do you expect to see some initial data from the triplet study and also on the mono therapy just wondering.

If we could hear a little bit about your latest thinking around opportunity there and path forward.

Lastly, just on the sub Q formulation.

How that will be phased into the expansion study.

Yeah, we're not guiding on our first data from the.

Triplet <unk> Lenalidomide study just started we'll guide on expectations for first data later note that it is a.

Yes.

Safety run in at two doses followed by ultimately the randomized phase if we go forward. So we will have some interim data, but we'll guide on timing for that at another point.

This came out of an empirical screen of combining various, you know, PD-1 with various other co-stimulatory targets.

And then all of our preclinical in vitro assays, the 104 was just the strongest in terms of activation of T cells, you know, that included in vitro, as well as, you know, our vivo mouse studies, where we just saw, you know, raging hot activity on the T cells.

<unk>.

So, I'll confess, we don't completely understand why this thing is different, but it was intriguing enough that we thought it was worth pursuing clinically.

So, it's a different beast than those other ICOS combinations.

They seemed to be pretty toxic, and they were hard to use.

The vastly different profile we have with our molecule, for example, it has no effector function in the FC, so we wouldn't expect it to deplete ICOS-positive cells.

We are hopeful that that allows us to have a differentiated profile that maybe toxicity limited the efficacy, because they couldn't get to enough dose, perhaps, of the historical molecule.

So, very different design, hopefully can overcome that toxicity limitation and see the activity there.

That's what the rationale was for the program.

Great, thank you.

The data is very strong there and so the landscape is changing and one of the things I want to point out is that what is considered relapsed refractory diffuse large b cell lymphoma has changed and so what we're noticing in our studies as we're seeing a lot of car T refractory patients coming into our studies, especially into the few large b cell lymphoma group, but we're still.

And then maybe just another one on Clomodomab.

Encouraged by our data so in terms of sub Q I think everybody suspects that.

Using <unk> will sort of change the the therapeutic index offer a better safety profile allow you to escalate faster and even higher in dose and so as we introduce sub Q. Later this year, we're going to see how good. It is and then make decisions on our current studies, which are currently IV.

Do we convert them over to <unk>, but again I think we need to see the early data first but I think everybody is encouraged with that.

Thanks.

In terms of our monotherapy data.

We're not guiding on our first data from the triplet, PLAMO, tafacitumab, lenalidomide study.

It just started.

We'll guide on expectations for first data later.

Planning to release additional monotherapy data from our I view IV study in our phase one that's in diffuse large b cell lymphoma, and Follicular lymphoma.

Note that it is a safety run-in at two doses, followed by ultimately the randomized phase if we go forward.

So, we will have some interim data, but we'll guide on timing for that at another point.

This will be IV.

I think that data again looks good.

Could the study's design in which way the data quality is good enough for registration, but would it be worth it since other companies are probably going to file.

Ivy sort of single arm data in the near future. We don't think monotherapy ultimately is the long term.

You know, you want to comment on how we're going to phase in the subcube and what the monotherapy, the rationale for continuing in the expansion is?

The long term player even frankly, the medium term play.

In <unk> trying to get into the B lymphoma landscape monotherapy data simply I think not going to compete against the myriad of combinations that are proceeding some of which have already shown glimmers of good activity from from early early studies, whether it's chemo combos, we're very excited by our chemo free regimen.

So the monotherapy opportunity as much as anything is.

This study does not about thinking that theres, a great opportunity there, but more about establishing that baseline of data and bringing forward enough data to make sure we can.

Demonstrate the rationale for our further studies exactly right now.

That's very helpful. Thank you very much.

Yes.

Your next question comes from the line of <unk>.

<unk> Vernon Burke your line is now open.

So, a couple things.

Great. Thanks, very much for taking my question.

Two from me first on the discontinuation.

So, the first thing about the landscape, you know, we are following that very closely, and I think one of the things is that CAR-T is definitely moving into second line, right?

The data is very strong there.

Paul.

Do the math I guess the <unk> target.

Endocrine tumors and you show some activity back.

The reason for this.

Particular indication.

Do you have anything to do with the commercial opportunity.

Because you learn something.

Sure.

Thank you Jamie.

And second question a quick one.

And our own to argue might be.

Yeah.

Should we.

Thanks very much.

So on the tech data Mab.

Historically in net and I think <unk> would face that as well here either long PFS and OS studies that are long to accrue in very long time and points out past two years in many cases, so we looked at the timeline for how that might go and it didn't seem like something that made sense and even in.

And so, the landscape is changing.

Net there is a shifting landscape. So that was really the driver for not wanting to pursue net and then Alan mentioned for why the challenge in small cell lung cancer potentially great opportunity that didnt make sense anymore based on what we were seeing could you repeat your question about our IL two I didn't catch it.

And, you know, one of the things I want to point out is that what is considered relapsed refractory diffused large B-cell lymphoma has changed.

And so, what we're noticing in our studies is we're seeing a lot of CAR-T refractory patients coming into our studies, especially in the diffused large B-cell lymphoma group.

Yes.

Can you update us with.

As you might know.

<unk>.

But we're still encouraged by our data.

Yes.

So, in terms of subcube, you know, I think everybody suspects that, you know, using subcube will sort of change the therapeutic index, you know, offer a better safety profile, allow you to escalate faster, and even higher in dose.

Oh, yes so.

The status of the study as we are currently in the phase one single ascending dose study in healthy volunteers and we expect to have data from that study later this year that is essentially going to be youre, a trifecta of safety Tolerability.

And so, as we introduce subcube later this year, we're going to see how good it is and then make decisions on our current studies, which are currently IV.

Biomarker data Youre looking for regulatory T cells to go up and for T. Effectors to not go up really.

And how long that lasts right the durability of it that that trio of biomarker data duration and Tolerability is going to tell us how really how we stack up I think against that same sort of correlated.

Similar data that was released after.

Do we convert them over to subcube?

Studies by some of the competition.

And it will also allow us to really be well set up to start our multiple ascending dose trial, which we're currently in preparation for and we'll also start this year and we'll give the details about that later.

Great.

Quick follow up.

Should you have a vaginal since you're mentioning sort of long.

Duration are you thinking maybe potential licensees to programs that you did for some others you discontinued.

Yes very much.

We're always open to finding ways for molecules, we make the potential to benefit patients and accrue value to the company.

Great. That's helpful. Thank you.

And our next question comes from the line of beat our lesson from Barclays. Your line is now open.

This is Jon on for Peter Thanks for taking the question just to follow up a little bit more on the discontinuation for your <unk> four.

Luxury so anything in that phase one data that you had developed so far that pointed to you would be more negative on the approach of a CLO for luxury or do you think it was just more based on the molecule you had and what you want to revisit making another <unk> four lag three and then I'll just also a little bit on the demand.

Just in light of discontinuation what is it that you're actually looking from that second half data that would point.

Two that you want to go forward and then further.

Do you think that this will be substantial enough update in second half for you to make that decision.

But, again, I think we need to see the early data first, but I think everyone is encouraged with that.

First of all the <unk>, it's not going to be enough data for the go no go it's going to be an initial look at safety and whatever efficacy. We can see from that a few handfuls of patients.

Across these different molecular subtypes.

And in terms of our monotherapy data, you know, we're planning to release additional monotherapy data from our IV study in our Phase I. That's in diffused large B-cell lymphoma and follicular lymphoma. This will be IV.

Tolerability in combination with aggressive chemo.

I think a very important thing.

To look at it really shows the potential but we don't anticipate efficacy go no go at in this year's update will have been less than one year into.

Since study start.

Obviously safety gate.

To give you a go no go at any time, whether you like it or not but we're optimistic that we can provide an update and.

Fully expect to continue the trial.

After that update but it will it will give people a read on what is really the potential for this new.

New way of targeting this pair of of receptors.

Going back to the <unk> four by lag three is that the molecule or the target pair is essentially what you asked I will say I don't know if anybody can address that given that I think there is only one of these it's ever been in the clinic and it was ours I can say that we don't plan on going back and making another one because as much as anything I think the landscape of competition has moved.

And it's very different from what.

We all expect it to be three years or four years ago, because you never know what it's going to be so we would not plan on making a new one but I don't think that reads on whether it's the target pair or.

Or the specific molecular design choices, we made I wish I could answer that.

You know, I think that data, again, looks good.

Great. Thank you for taking my questions congrats on the quarter.

Our next question comes from Brian If David Dai from SMB to your line is now open.

So could you share with us the physician feedback on the tolerability profile, especially in the context of the combination if there's different prostate cancers?

Yeah, we don't think monotherapy ultimately is the long-term play or even, frankly, the medium-term play in CD20, CD3s trying to get into the B-lymphoma landscape.

Great. Thanks, taking my questions. So one question on the daily amount. So we saw in the data that there were some modest level of equivalent to a rash and pruritus around 31% and 46%, but could you share with us the physician feedback on the Tolerability profile, especially in the context of the combination and the various different.

State cancers.

So just to make sure we heard your question right, you were commenting that the most common AE we presented at CITSI for Voodalumab last year, CITSI was rash at around 30%.

So.

Just to make sure we heard your question right you were commenting that.

The most common AE, we presented at <unk>.

Last year <unk> was rash at around 30% and you're wondering how that might.

What might happen with chemo in terms of synergistic Tox is that what youre asking that's correct, yes, that's correct.

Would you expect to see us through a higher.

Tolerability or safety issues, when you combine with <unk>.

And you're wondering how that might work, what might happen with chemo in terms of synergistic talks?

The companys yet.

So yes, let me just sort of generally talk about the Tolerability of 707, which we are very impressed with I mean.

We're very excited by our chemo-free regimen.

So the monotherapy opportunity, as much as anything, continuing the studies, is not about thinking that there's a great opportunity there but more about establishing that baseline of data and bringing forward enough data to make sure we can demonstrate the rationale for our further studies.

Exactly right.

Remember when you give a PD one <unk> four combination with the two drugs independent like Nemo and AP.

A third of patients develop colitis and have to discontinue so much so that they usually just give the Nemo and then they give the <unk> for a short period of time four courses I think is the latest thinking right now so when we looked at our data from <unk>, we had a gi diarrhea rate around 10%, which.

He was very tolerable much lower and rash was the most common AE.

For oncology patients rash is not a huge.

It's not a important toxicity, it's not going to cause you to discontinue now whether you would expect to see synergy with chemotherapy.

For that toxicity profile, probably not I mean, it's still early but if you think about it rashes are often treated with low doses of methotrexate, depending on the type of rash. So.

Yes for autoimmune diseases and so forth.

Psoriasis.

That's the old base. So I don't think we will see synergy in terms of toxicity, but we don't know its still early.

Is that what you're asking?

Think that was your question right David.

That's correct.

That's right. Thanks, so much for the for the answer and then another question on a one off or maybe just help me understand some of your biomarker strategy is to identify the responding tumor types for the program.

Yes, that's correct.

So, yeah, let me just sort of generally talk about the tolerability of 7-1-7, which we, are very impressed with.

I mean, remember, when you give a PD-1 CTLA-4 combination with the two drugs independent, like NEVO and IPI, you know, a third of patients develop colitis and have to discontinue, so much so that they usually just give the NEVO and then they give the IPI for a short period of time, four courses, I think is the latest thinking right now.

So when we looked at our data from CITSI, you know, we had a GI sort of diarrhea rate, around 10%, which is very tolerable, much lower.

And rash was the most common AE, and, you know, for oncology patients, rash is not a, huge, it's not an important toxicity, it's not going to cause you to discontinue.

Now whether you would expect to see synergy with chemotherapy for that toxicity profile, probably not.

I mean, it's still early, but if you think about it, you know, rashes are often treated, with low doses of methotrexate, depending on the type of rash, so yeah, for autoimmune diseases and so forth, like psoriasis.

So that's the old days.

I think our strategy for identifying the responding tumor types is really about response about resist response I think we have to be stringent about that we've obviously characterized biomarkers because understanding the mechanism hope you glean insights into dose selection. The rationale for maybe if you see some kind of activity or toxicity in certain patients.

So I don't think we'll see synergy in terms of toxicity, but we don't know.

But no it's about it's about.

The kind of tumor response, you see not really the biomarkers.

Got it thank you so much.

It's still early.

That's very helpful.

Your next question comes from the line of David Nearing Martin from Wedbush Securities. Your line is now open.

I think that was your question, right, David?

Thank you very much.

That's right.

Your next question comes from the line of Zeke Yangju from Varenburg.

Well, thanks so much for the answer.

Thanks for taking the question.

The plan for <unk>.

Second.

And then another question on 104, maybe just help me understand some of your biomarker, strategies to identify the responding tumor types for the program.

And speaking of competitive profiles.

It's a pretty competitive space.

I think our strategy for identifying the responding tumor types is really about response.

What do you think you need to hit with the Triple combination in terms of.

Our response rate.

Consider.

Advancing the program further.

It's about resist response.

Yes, I think that it is.

Still really hard to say for most of the studies because I think there is only one study we've seen a significant number reported just top line from the recent abbvie release, where they had about a 60% or in a 40% CR rate for that that are relapsed refractory there'll be cell population.

I think we have to be stringent about that.

We've obviously characterized the biomarkers because understanding the mechanism can help, you glean insights into dose selection, the rationale for maybe if you see some kind of activity or toxicity in certain patients.

I think that sort of sets the minimum bar honestly for us because it is a similar population and so how much you can go from there we know that <unk> starts with about a 40%.

Our rate and about a 60% or.

Yeah, and I think Theres a couple of things. So the L. Mind study is probably a good benchmark of what wed expect to see with just half and led by itself granted the landscape is changing a little bit but what's nice is remember we will have this run in so if we think the study may be underpowered, we can adjust the size of our changed strategy in the second part of.

The study.

Maybe a quick follow up.

Yes.

Not to.

Give too many hypotheticals, but.

Pushing those patients to see are more important to you or is it just kind of generally the overall response rate.

More important for you when you have such as the.

Prospects.

Yes, a good question I think thats more of a qualitative answer I think CR is always important right. So I think youll get responses, but when you look at the competitive landscape I think the power of the car T has been that <unk> been able to push patients into CR that are durable right and the question is can buy specifics do something similar to that.

Alright, and Thats, why we think that.

The potential for additive or maybe synergistic activity with a CD 19 targeting NK cell recruiting high DTC antibody.

It's something that just adds another avenue that avoids the toxic chemo, maybe lets us move that needle.

Sure.

Okay.

Got it.

Thanks.

Thank you there are no further questions at this time, our lawn I'll like to turn the call over back to <unk>.

But no, it's about the kind of tumor response you see, not really the biomarkers.

Your line is open.

Great.

Thanks very much for taking my question.

Thank you so much.

So, two from me.

Thanks, very much for joining us today, everybody and we look forward to updating you again in the near future.

Your next question comes from the line of David Nerengarten from Red Bush Securities.

First, on the discontinuation, of Dutamab, I guess the SSTR2 is the risk target in a neuroendocrine tumor, and you show some activity there.

Your line is now open.

What was the reason for discontinuity in that particular indication?

Hey, thanks for taking the question, and we'll just switch to Primo for a second.

Does it have anything to do with the commercial opportunity, or is it really because you learned, something about the CDTs that engage in these kinds of tumors?

Speaking of competitive profiles, you know, it's a pretty competitive space.

My second question is a quick one.

What do you think you need to hit with the triple combination in terms of a response, rate to consider advancing the program further?

Can you help us understand the IL-2, a program you are developing, with that state and how long should we be able to see the data?

Your next question comes from the line of Peter Lawson from Barclays, your line is open.

Yeah, I think that it's still really hard to say from most of the studies, because I, think there's only one study we've seen a significant number report. It was just top-line from the recent AbbVie release, where they had about a 60 percent, OR and a 40 percent CR rate for that relapsed refractory DLB-CL population.

Thanks very much.

This is Jiayuan for Peter.

I think that sort of sets the minimum bar, honestly, for us, because it's a similar population.

So, on the Tidutamab stop in neuroendocrine tumors, or NET, I think it was as much as anything, not so much the commercial opportunity per se, but rather the very, very long clinical trials you would have to do to achieve them, where historically in NETs, and I think Tidutamab would face that as well here, there are long PFS and OS studies that are long to accrue and very long time endpoints, out past two years in many cases.

Thanks for taking the question.

And so how much you can go from there.

So, we looked at the timeline for how that might go, and it didn't seem like something that made sense, and even in NETs, there's a shifting landscape.

Just to follow up a little bit more on the discontinuation for your CTLA-4 by LAG-3, is there anything in that Phase 1 data that you had developed so far that pointed to you being more negative on the approach of a CTLA-4?

Hi.

We know that taposidimab linoleumide starts with about a 40 percent CR rate and about, a 60 percent OR.

So, that was really the driver for not wanting to pursue NET, and then Alan mentioned for why the challenge in small cell lung cancer, a potentially great opportunity, that didn't make sense anymore based on what we were seeing.

Or do you think it was just more based on the molecule you had and what you want to revisit making another CTLA-4 LAG-3?

Yeah, and I think there's a couple of things.

Could you repeat your question about our aisle two?

And then just also a little bit on the Voodalabab, just in light of the discontinuation, what is it that you're actually looking from that second half data that would point to you that you want to go forward?

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

So, you know, the L-Mind study is probably a good benchmark of what we would expect to, see with just Taff and Len by itself.

I didn't catch that.

And then further, do you think that this will be a substantial enough update in second half for you to make that decision?

Granted, the landscape is changing a little bit, but what's nice is, remember, we'll have, this run in.

Yeah, just kind of, can you update us with the status right now?

First on the Voodalabab, it's not going to be enough data for the go-no-go.

Thank you.

So if we think the study may be underpowered, we can adjust the size or change strategy in the second part of the study.

Oh, yeah.

It's going to be an initial look at safety and whatever efficacy we can see from that few handfuls of patients across these different molecular subtypes.

There are no further questions at this time.

And maybe a quick follow-up, I mean, you know, not to give too many hypotheticals, but, you, know, is, you know, pushing those patients to CR more important to you, or is it, you know, kind of generally the overall response rate that's more important for you when you assess the prospects?

So, the status of the study is we are currently in the phase one single ascending dose, study in healthy volunteers, and we expect to have data from that study later this year that is essentially going to be your trifecta of safety tolerability, the biomarker data, you're looking for regulatory T cells to go up and for T effectors to not go up, really, and how long that lasts, right, the durability of it.

The tolerability in combination with aggressive chemo is, I think, a very important thing to look at.

Yeah, it's a good question.

That trio of biomarker data, duration, and tolerability is going to tell us how, really, how we stack up, I think, against that same sort of correlated, similar data that was released after SAD studies by some of the competition, and it will also allow us to really be well set up to start our multiple ascending dose trial, which we're currently in preparation for, and we'll also start this year, and we'll give the details about that later.

It really shows the potential.

I think that's more of a qualitative answer.

Great.

But we don't anticipate efficacy go-no-go in this year's update.

I think CR is always important, right?

Just a quick follow-up on the P2MF, since you mentioned sort of long trial duration, are you thinking maybe potentially about licensing these two programs as you did for some others you discontinued?

It will have been less than one year since the study started.

So, you know, I think you'll get responses, but, you know, when you look at the competitive, landscape, I think the power of the CAR-T has been that they've been able to push patients into CR that are durable, right?

Thanks very much.

Obviously, safety data can give you a go-no-go at any time, whether you like it or not.

And the question is, can bispecifics do something similar to that, right?

You know, we're always open to finding ways for molecules we make to potentially benefit patients, and, you know, accrue value to the company, so I would say everything's on the table.

But we're optimistic that we can provide an update and fully expect to continue the trial after that update.

And that's why we think that the potential for additive or maybe synergistic activity, with a CD19-targeting NK cell-recruiting high ADTC antibody is something that just adds another avenue that avoids the tox of chemo that maybe lets us move that needle, right?

I'm not going to guide to that.

But it will give people a read on what is really the potential for this new way of targeting this pair of receptors.

Yeah.

I would say it's not a high priority for us, for these two programs, to find partnerships where I think we've got other fish to fry, but never say never.

Going back to the TLA-4 by LAG-3, is it the molecule or the target pair is essentially what you asked?

Got it.

I will say I don't know if anybody can address that, given that I think there's only one of these that's ever been in the clinic and it was ours.

Yeah.

I can say that we don't plan on going back and making another one, because as much as anything, I think the landscape of competition has moved, and it's very different from what we all expected it to be three or four years ago, because you never know what it's going to be.

Thanks.

So we would not plan on making a new one, but I don't think that reads on whether it's the target pair or the specific molecular design choices we made.

I wish I could answer that.

Great.

Thank you for taking the question.

Congrats on the quarter.

Your next question comes from the line of David Dye for SMBC.

Your line is now open.

Great.

Thanks for taking my questions.

So one question on the DALY map.

So we saw in the CITSI data that there were some modest level of who went to rash and pruritus, around 31% to 46%.

Could you share with us the physician feedback on the tolerability profile, especially in the context of the combination, if there's different prostate cancers?

So just to make sure we heard your question right, you were commenting that the most common AE we presented at CITSI for Voodalumab last year, CITSI was rash at around 30%, and you're wondering how that might work, what might happen with chemo in terms of synergistic talks?

Is that what you're asking?

That's correct.

Yes, that's correct.

You know, would you expect to see a sort of higher, you know, tolerability or safety issues when you combine with different combinations?

So, yeah, let me just sort of generally talk about the tolerability of 7-1-7, which we, are very impressed with.

So when we looked at our data from CITSI, you know, we had a GI sort of diarrhea rate, around 10%, which is very tolerable, much lower, and rash was the most common AE, and, you know, for oncology patients, rash is not a huge, it's not an important toxicity, it's not going to cause you to discontinue.

Now whether you would expect to see synergy with chemotherapy for that toxicity profile, probably not.

I mean, it's still early, but if you think about it, you know, rashes are often treated, with low doses of methotrexate, depending on the type of rash, so, yeah, for autoimmune diseases and so forth, like psoriasis, and so that's the old days.

So I don't think we'll see synergy in terms of toxicity, but we don't know, it's still, early.

I think that was your question, right, David?

That's right.

Well, thanks so much for the answer.

And then another question on 104, maybe just help me understand some of your biomarker, strategies to identify the responding tumor types for the program.

I think our strategy for identifying the responding tumor types is really about response, it's, about resist response.

I think we have to be stringent about that.

Thank you so much.

Your next question comes from the line of David Nirengarten from Red Bush Securities.

Your line is now open.

Hey, thanks for taking the question, maybe I'll just switch to Primo for a second.

Speaking of competitive profiles, it's a pretty competitive space.

What do you think you need to hit with the triple combination in terms of a response, rate to consider advancing the program further?

Yeah, I think that it's still really hard to say from most of the studies, because I, think there's only one study we've seen a significant number report, it was just top line from the recent AbbVie release, where they had about a 60% OR and a 40% CR rate for that relapsed refractory DLBCL population.

I think that sort of sets the minimum bar, honestly, for us, because it's a similar population.

And so how much you can go from there.

We know that taposidimab linoleumide starts with about a 40% CR rate and about a 60% OR.

Yeah, and I think there's a couple of things.

So, you know, the L-Mind study is probably a good benchmark of what we'd expect to see, with just TAF and LEND by itself.

Granted, the landscape is changing a little bit, but what's nice is, remember, we'll have, this run in.

So if we think the study may be underpowered, we can adjust the size or change strategy, in the second part of the study.

And maybe a quick follow-up, I mean, you know, not to give too many hypotheticals, but, you, know, is the, you know, pushing those patients to CR more important to you or is it, you know, kind of generally the overall response rate that's more important for you when you assess the prospects?

Yeah, it's a good question.

I think that's more of a qualitative answer.

I think CR is always important, right?

And the question is, can bispecifics do something similar to that, right?

Yeah.

Got it.

Yeah.

Thanks.

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