Q2 2022 Xencor Inc Earnings Call
The conference will begin shortly to raise your hand during Q&A you can dial star one one.
[music].
Good afternoon.
Thank you for standing by and welcome to Zen cores second quarter 2022 conference call at.
At this time all participants 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 recorded at the company's request.
Now I would like to turn the call over to your speaker today, Charles Liles head of corporate Communications and Investor Relations.
Yeah.
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 Dot Com with me on the call are battle that yet President and Chief Executive Officer, Allen Yang Chief Medical Officer, John <unk>, Chief Financial Officer, and John does relate chief scientific.
Officer.
Open up the call for your questions after our prepared remarks before.
Before we begin I would like to remind you that during the course of this conference call <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 program.
Forward looking statements are not historical facts, but rather are based on our current expectations and beliefs are based on information currently available.
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, Charles we've used our array of modular approach the engineering tools to create a broad internal development portfolio in oncology not immune disease, which allows us to take multiple simultaneous shots on goal in the clinic. Our intent remains using proof of concept data from our early stage studies to guide, which programs will be there, which we terminated in which we partner.
So we use our resources on those programs with the greatest potential for success and make room in our portfolio for the next wave.
Specifics in engineered cytokines.
The plug and play nature of our <unk> technology, and our ability to generate biologic drug candidates rapidly and efficiently provides us with many opportunities to generate revenue from strategic licensing and collaboration agreements.
Which is allowed us to avoid accessing public markets for capital for over four years.
Supporting our development worker, three royalty producing marketed products, including Altamira, which incorporates our extended FC domain to enhance antibody half life and allow for longer duration of action less frequent dosing and reduce patient burden of therapy compared with correctly antibody.
<unk> recently received a positive opinion from <unk> in Europe for generalized myasthenia gravis.
Astrazeneca has guided to GMP regulatory decisions in the EU and Japan as well as regulatory submissions for Neuromodulators optica spectrum disorder in the U S EU and Japan all of this year.
Now, we're looking externally for tools and assets that can expand our technology for creating new drug molecule and complement our pipeline candidates yesterday, we and our new partner Caris Life Sciences announced the target discovery collaboration of license agreement to create X snap bi specific or multi specific antibody directed directly against uptick.
Three novel targets discovered with terraces unique human tissue bank in bioinformatics approach were finding addressable tumor markers.
Our goal is to use our protein engineering to create molecules tackle hard to address biology, and that we could potentially advance to approval and to market if the data and environment supported it.
And our two newest programs are first X plus one CD three by specific in our first few <unk> bi specific T cell engagement and now advanced into first in human studies.
I'll now turn the call over to Allen Yang our Chief Medical officer to update on our clinical portfolio and cover up can be cleared.
Thanks, Pavel last quarter, we went through our whole clinical portfolio, but today, we will briefly review upcoming plans for our data presentations, our clinical data presentation at <unk> and some recent and near term study starts.
We plan to present data from three studies through the end of the year first we expect to present data from the single ascending dose of healthy volunteer study ex Maffei six four are wholly owned IL, two FC cytokine infusion, which targets regulatory T cells.
That we are developing in patients with autoimmune disease. We also plan to initiate in the coming months and multiple ascending dose study in patients.
<unk> for the CD 20 by CD three by specific antibody Pamona map, we will present data from the expansion cohorts in the ongoing phase one IV monotherapy study in patients with advanced non Hodgkin's lymphoma or plans to introduce subcutaneous dosing into the study are underway and additionally, our phase III study of the Triple combination.
With <unk> and Revlimid is ongoing.
For our PD, one <unk> four by specific due to Allomap will also present some early data from the first of our two phase III studies.
Chemotherapy combination in patients with metastatic castrate resistant prostate cancer and our second phase II study in patients with clinically defined high risk Medicare static castrate resistant prostate cancer and certain gynecological malignancies is now dosing patients.
This June at <unk>, we reported initial data from the monotherapy escalation portion of the phase one study of our PD one iqos bi specific antibody ex map 104 in patients with advanced solid tumors ex map 104 was well tolerated and exhibited the same safety profile compared to other clinical stage programs.
We observed anti tumor activity and biomarker activity consistent with T cell engagement we.
We are currently enrolling the expansion portion of our phase one study in combination with <unk> in parallel cohorts of several different advanced solid tumors.
Now on to our clinical trial starts.
First we recently initiated a dose the first patient in a phase one study of <unk> 109, our E&P three by CD three by specific antibody in patients with advanced renal cell carcinoma ex Matt eight nine uses our <unk> to plus one multivalent format for enhanced tumor target selectivity.
<unk> antibody has built with our two plus one format, including $8 nine have shown preferential killing of tumors with high target antigen expression relative to normal cells, which is particular tiny tool for developing drug candidates targeted to solid tumors.
Thanks, Matt 809 is our first two plus one by specific to enter the clinic. However, Amgen Similarly engineered steep one targeting by specific is already advancing through phase one and has shown encouraging early PSA response data, we look forward to following its progress as well.
Next we now have an open IND and are now initiating a phase one study of X map eight O eight RMB seven <unk> III by CD 28 bi specific antibody are first CD 28 targeting molecule in combination with <unk>.
CD 20 eights are new classify specific engineered to provide conditional co stimulation of T cells through the <unk> receptor when the molecule is balance of tumor cells with the goal of enhancing activity of CD, three bi specifics and checkpoint inhibitors.
I'll have more to say about this study in the coming months.
Now with that said I'll hand, the call over to John <unk>, Our CFO to review our financial highlights.
Thank you Alan.
Total revenue for the second quarter and the first six months of 2022 was $31 million and $115 6 million respectively.
Revenue for the second quarter and first half of 2022 was primarily royalty revenue from our beer and lexan partnerships related to sales of the trove Mab and ultimately respectively.
Revenue from these royalty streams and income from other partnerships and collaborations help us set our spending on operations and clinical programs.
For the first six months of 2022, the total revenue that we received fully funded our operations and further strengthen our balance sheet.
Total cash equivalents receivables and Michael debt Securities at June 30 totaled $679 7 million, which is approximately $50 million more than the $664 1 million balance reported at the beginning of the year.
We are updating our year end guidance and now estimate they will end 2022 with between 550 and $575 million in cash cash equivalents receivables and macro securities and will continue to guide that we will have sufficient cash to fund our R&D programs and operations through the end of 2025.
Refer you to our press release this afternoon and through our SEC filings for further details about our financial results.
With that wed now like to open up the call for questions operator.
Thank you.
To ask a question you will need to press star one one on your telephone.
Please standby will compile the Q&A roster.
Our first question comes from Mara Goldstein with Mizuho. Your line is now open.
Great. Thanks for taking the question.
Thank you thanks, Tony our three rather.
First is on.
Thanks, Matt.
Maybe just talk a little bit about.
The target there.
<unk> HD target just given what we've seen in the in that on the competitive landscape on the AE profile perspective.
On Videla, Matt can you maybe.
Give a little bit of color on.
Which of the groups do you anticipate having data on and and how many patients we should start thinking about so the data disclosure there and just lastly on like Paris arrangements, you have some financial obligations milestones and whatnot when should.
Should we anticipate that something would be required to be paid from that program.
Alright. Thanks.
I guess I'll start maybe with the Claris one.
There was an upfront payment.
What percentage of the total disclosed basket of payments, but I think the subsequent ones are going to be driven a little bit later into the collaboration we're at the start taking these these initial information on these targets and starting with validated.
February efforts then.
Okay.
Okay.
I think it'll be it'll be a little while I think before we start hitting those obligations.
Okay, and then maybe John do you want to touch on I guess, you're referring for Ada way to both CD 28, <unk> hundred 83 of those targets.
Yeah.
Most specifically the 17th Street target just what we've seen over the last few months.
Some of that.
Yes, yes.
Yeah. Thanks, So first of all we like be 73 as a target.
We selected up because it is very bright and very broadly expressed across a lot of different solid tumor histology.
I assume youre, referring to some of the Aes that were seen disclosed by Macrogenics in the head and neck cancer.
Cancer patients.
We don't know how to interpret that the drug conjugates haven't seen those same kinds of events.
Either the Daiichi Sankyo Macrogenics program.
Do you want to add anything to that.
We don't have any details around where the fleet is best for them, whether they are related to the product they seem to say that that cancer.
Has a lot of bleeding events and in their phase one they didn't have that many bleeding of that so we're not concerned about it at this time.
Alright, Great and then just on the <unk> and the different cohorts, what you anticipate you might share.
So it's going to be data from the patients that came in right. So it's.
All the cohorts recruited at the same time and note that the great majority of patients are receiving the same.
Therapy combination of a platinum plus the taxol with Hu <unk>, except for the small portion of the proceeds based on the keynote <unk> PARP inhibitor or where there is no chemo and it's just the moniker the great bulk are going to be.
The chemo combo and the real point of this data is that initial look at can we combine a dual checkpoint blockade of PD, one particularly for.
How does it look what kind of results are we seeing and what's the path forward for trying to get chemo combos into dual checkpoint blockade. So it will be a few handfuls of patients.
Thats the disclosure we plan it will be spread across the cohorts, but again almost all patients are getting the chemo.
Okay. Thanks, I appreciate it I'll hop back on.
Thank you.
Thank you.
Our next question.
Comes from David dye.
SMB CLEC your line is now open.
Okay.
Hi, I'm sorry.
Yeah, Alright can you hear me okay.
Yes.
Great. Thanks for taking my questions.
A couple of questions.
So first question is around the alpha team obtaining our AFC program yet.
Thanks Jordan.
So the FDA has accepted our BLA from a competitive program in bladder cancer, how should we think about potential view through to your <unk> program could you maybe share with us some of your depreciation of your IL 15 assay can get you there.
I have a follow up after.
Sure I guess I'll address that question. So we understand the BLA in question is for a Super agonist IL 15.
Scepter Alpha fusion.
In.
Non muscle invasive bladder cancer, so that is not a systemic therapy, it's a therapy given in combination with BCG.
Through cystoscopy right into the bladder so it's not a systemic therapy and I think that that maybe relates to the different fundamental difference and design of the molecule ours was in here to extend 306 are IL 15, as well as our whole family of cytokine therapies.
Engineered with dramatically reduced affinity to the signaling receptor and reduced potency to smooth out that activity time curve. So you don't have the big spikes of activity early on that can drive toxicity and you don't have the big think of receptor mediated clearance and lowering the duration of action.
So that's a fundamental difference to a super agonist design, but just trying to amplify things, but I think we're committed to the systemic route and to being able to be used broadly and widely across many different tumor types, where not just enrolling in solid tumors with genentech in the phase one dose escalation in combo with <unk>, the PD lone inhibitor, but now.
Does that take us started the combo with <unk> in myeloma.
We're going to be starting a study of our <unk>, we will disclose the details of that in the indication in the coming months and we know Genentech is working on further studies, so I think systemic versus.
Local deliveries are pretty fundamental difference.
So I'm not sure how much read through there is.
IL 15 to IL 15.
Got it Thats really helpful. So second question is for the IL two <unk> program.
Support program.
We know that is currently in a healthy volunteer trial, but any updated thoughts on which autoimmune indications that youre planning to move the program into.
There is a lot of potential indications for <unk> T. Reg amplifier, not a lot of deep clinical data, though from.
Anybody really about what indications of T. Reg.
T. Reg therapy is going to be able to treat gist glimmers of information that was recent information released by a competitive program that seemed to show from a very small cohort of patients.
Promising data randomized against placebo in atopic dermatitis.
Certainly exploring.
Jeremy indications and and looking across the spectrum as information starts to come out from competitors at what at what to add to the mix. We've got a lot of work we are going to be disclosing. The initial indications are doing in our multiple ascending dose study in patients that we do expect to start within the next few months.
Shortly and so we'll be able to guide a lot more when we have our first data readout. This half of year from the single ascending dose in healthy will also guide on the specific indications shortly.
Got it that's really helpful. Thanks, so much for the color.
Thank you.
Next question comes from Caveri Pullman with BTG. Your line is open.
Yes. Good afternoon, thanks for the update and for taking my question, maybe just one for me in terms of format for CD three T cell engaging you recently discontinued development of to do the math does that mean Q1 format are the way to go for solid tumors and how would you compare it to two.
Two plus two formats in the clinic.
So I think it's going to be tumor antigen by tumor antigen I think when you've got one where you want a separate binding from healthy to normal healthy normal tissue with low expression in high expression on tumor two plus what is almost certainly going to be the way to go again, you need to do the experiment and look at the details.
I think theres going to be cases, where that won't be such a cleaner simple situation.
We're still learning a lot from it I think we think theres a lot of promise in two plus ones and so we're certainly pursuing them because in many cases, you do have that high low expression on tumor versus healthy.
As for two plus two for John I'm, not familiar with too many there've been a few historically tried I don't know if that much clinical data I've seen from those wells.
Most people avoid having two binders to CD three because you're worried about that afflict. The T cell activation, it's definitely not a direction that we're pursuing.
Internally as an ore.
Got it thank you.
Thank you.
Next question comes from Charles Zhou with Guggenheim Partners. Your line is now open.
Hello can you hear me.
Yes, okay.
Great. Yes, thanks, guys for taking the questions and congrats on the progress of my first one on <unk>.
<unk> hundred nine given that it's a <unk> T cell engagement as well as the ongoing buzz around FDA project Optimists, how should we think about progression of dose escalation in exploration, particularly when you compare how you might progress with <unk> 109 relative to how historical C. III T cell engaging.
Dose escalation has been conducted previously thanks.
Well I think it's way more informed by the data and the science down if there is data and science to go from I mean, John you've been dug into this more than any of us about.
About I think the project Optimists, just it just puts a little bit more pressure on it.
And having enough biomarkers in your study.
That you can really defend that.
Pick the optimal dose but of course, we're still going to.
Mobile fashion standards as well so what's the maximum tolerated dose.
How much how much crs is happening at different dose levels.
I think the biggest learning is the knowledge about priming doses and step up doses.
The magnitude of priming dose you need and what Biomarkers. If you look at to set that dose.
Relative to what we thought maybe five years ago priming doses are lower than you might have thought and they can be quite a lot lower than your ultimate dose and you can still get there fast. So I think we all expect to be able to move faster because theres a lot more confidence in these these serum biomarkers like IL six levels and how can you can you step up to the mid.
Gate Crs like we I think we've been pretty successful.
Certainly numerous other programs that are competitors or collaborators have done yes, maybe I can add something here. So in my experience what I've observed that it's still early days on this project optimists as that usually precedes threes. The agency's requiring you to explore two different doses in terms of your efficacy or expansion.
I don't know if they'll keep start going about it seems to be like the MTBE immediate dose slow or less seems to be efficacious with maybe lower toxicity.
I'd just say for the 809 study we have a lot of learnings from our previous studies.
Lot of flexibility to Biomarkers are pretty novel design is pretty nominal so it gives us a lot of flexibility in terms of understanding our guests when we go into that expansion.
Got it great Thats really helpful. Thanks for all that color and then maybe just one follow up question regarding Dow on that I guess with respect to your upcoming data readout.
Much will we be able to glean from that data set and given.
The wide spread of different patient populations characterized by molecular subtype youre enrolling will we be able to kind of determined I guess I should say would you be able to determine particularly interesting subset.
Subsets of patients either from a clinical or strategic perspective for a longer term development. Thanks.
This data read out it's going to be too early but too few patients to make any kind of conclusions about the different.
Different subtypes, but remember these are all still metastatic CRP C patients.
And they've all gone through essentially the same therapies prior and so there is no need to consider them differently outside of their their medical.
Outside of this therapy, we're giving US again, the bulk of them chemo plus <unk> you can think of those as a group and then as we accrue greater numbers, we will see if any patterns emerge right. But this initial look will be I think too early to make any conclusions about that and we will just give us an early look at.
Is there a.
On efficacy Tolerability data for this initial regimen, we've come up with which is simultaneous basketball chemo and due to that.
Great that makes sense. Thanks for taking all my questions and look forward to to your upcoming Readouts.
Thank you.
Thank you.
Our next question comes from Edward <unk> with Piper Sandler Your line is open.
Great. Thank you very much and thanks for taking.
My question will fundamentally exciting by Tesco I Wonder if we get a sense just with respect to the.
So the kind of work that you're doing.
Obviously this will become a big focus for the company.
The partnership workflow trial.
Yeah.
So maybe you can tell us sort of at a high level, how you think ex.
Really differentiate in this space.
There's a lot of competitors, who are looking at basking in other type of loans.
Just want to understand.
Differentiating and ultimately what to do with maybe some of the other.
None.
Okay.
Yes.
I'll start maybe John you can jump in but the insights that our team had the Johns team had with debt at cytokines toxicity and overly fast clearance relative to what you want a drug that is it.
By their naturally very high potency and that you can dial that potency down and create a completely different pharmacodynamic and pharmacokinetic profile and how we use that for making the drugs in the future of the platform. There's a lot of ways to go but I think that's the key insight and differentiation.
I mean, that's the unifying theme.
<unk> be about it is these these long acting lower potency cytokines are so much better tolerated not our experience so far.
That it gives us tremendous combination potential as well you could think about combining these with our CD three engages finding them with checkpoint inhibitors, combining with Encana engages.
There's just a ton of potential there and I think there's a simplicity there where the challenge of really complex protein engineering efforts like you see with masking approaches.
Conditional activation approach is theres a lot of biochemical pieces within the drug molecules that have to work exactly based on assumptions about the biology going on in the body that are just that assumption I think the simple sort of universal approach. We think is really attractive and we've already applied into two cytokines that are in the southern part.
Third one is coming on behind that our IL 12.
IL <unk> program, that's in preclinical and we're also doing targeting of these anti.
Antibody domains fused so.
We think that this general low potency platform with its tolerability and half life, let's just start thinking about cytokines. There is a real drug development widgets and no longer these esoteric molecules.
Okay.
Appreciate that.
Helpful.
Thank you.
Our next question comes from the line of <unk>.
Gregory <unk> with RBC. Your line is now open.
Hi, This is neena on for Greg Thanks for taking our questions.
Two from US first on <unk>.
Just curious on your thoughts on the data from let's say 28 by specific in our states today, and how that referred to the clinical potential safety considerations.
As well the combination strategy with Penn Brown.
And then secondly, maybe just on fixed.
Six four.
Further initial data in healthy volunteers, what are the level of changing T. Regs and key factors do you think you could expect to see to give you confidence clinical potential.
Okay.
I'll, let I'll, let John take it away since our CD 28 platform is really something that grew out of the work that is he led his team, but let me answer on 564 really quick I think we've seen what our competitors have.
As delivered in their initial data disclosures from their single ascending dose studies in a little bit of a multiple dose study.
<unk> sort of a little bit north of five fold increase in <unk> as you see it often decaying asked a couple of weeks.
And reasonable tolerability of the programs vary a bit in that I think the bar we set for ourselves is to be at least as good as the best in class. So I think north of that kind of amplification of T. Regs, it's got to be selective no T effectors and.
Good Tolerability and we're hoping that our design gives us a longer half life.
Yes.
PSM ACD 28 data that was disclosed today.
Early days right small number of patients but.
We're actually pretty excited to see what they are saying about it.
Put some wind in our sails on either way.
A lot of potential in that class and it's kind of the first clinical validation that you could really move the needle there.
Yes, we view that as clear proof of concept that you can improve PD, one therapy checkpoint inhibitor therapy with TD 28 co stimulation that's been seen in humans and I think that's a great step for the field and we're excited to have an agent that.
Got an open.
And it's going to be in the clinic in the coming months.
The great place to start.
Great. Thank you very much.
Okay.
Thank you.
Our next question comes from Ed Sir the route with BMO. Your line is now open.
Great. Thanks for taking the question just one quick one for me.
The Delta.
Data that.
You'll be disclosing in the second half just trying to think about the right comparator for the combination with chemo is the right.
Way to think about this as sort of chemo like Joe tunnel Docetaxel in patients with metastatic castrate resistant prostate cancer is that the right way to think about this upcoming data set from an efficacy standpoint.
I know you were asking about the chemo comparator the right one.
Is there something that got garbled.
The phone can you repeat.
What you stated was the right reference frame.
Jeff Donna just ton of post off the capsule.
<unk>.
Yes, so I think youre, asking like what to expect and how to benchmark the data that we'll be presenting so.
Think comparison with a PD one in combination with Docetaxel is a fair comparator, but not actually accurate 100%.
Remember from our phase one data we found very good tolerability of our PD one <unk> four.
And we thought we could combine it with a very aggressive chemo regimen, the best chemo regimen for prostate cancer, which is a platinum plus Cabo taxol.
Docetaxel I think is just a single agent chemo in a lot of people use that.
In terms of benchmarking it other therapies I mean, you may want to compare it to the Cabozantinib.
A T cell combo as well that response rate I think was 18% centrally reviewed so I wouldn't think about comparing it to those agents directly but I think that gives you a ballpark of how to develop it in the future.
Without giving out too much detail.
Yes. Thank you that's very helpful. Thank you sure.
Thank you.
Our.
Question.
Comes from Jonathan Chang with SBB Securities. Your line is now open.
Hi, this is.
Hi, This is Matt <unk> on for Jonathan Chang Congratulations on the recent progress and thanks for taking my questions.
Just a first question.
The keynote <unk> one data this morning, which is the <unk> chemo in.
RCP.
Which missed on OS and radiographic PFS do you have any updated thoughts on use of PD one targeting agents in this setting.
I think it's clear that the limited activity that PD. One agents have had in <unk> has been no repeatedly confirmed I think it shows you that they are not highly active and I think thats why we feel convinced that our dual checkpoint inhibitor with PD one and.
<unk> four blockade simultaneously.
Is it a different hypothesis that really Meredith.
I think also it shows you the encouraging.
Typically you see with the CD 28 by specific that we saw disclosed earlier today and on top of the PD one agents Shelly.
Number of responses out of a very small patient cohort. So again very early data I think quite encouraging brokerage startup standpoint, and note that we have not just for <unk> coming to the clinic soon and piece of <unk> is highly expressed in prostate cancer and so that's obviously a place where considering looking that in combo with <unk>.
Our partner Janssen has a CD 28 against a prostate.
Restricted antigen that is going to be behind us and timeline will be the first in the clinic with our platform, but they're also excited about so I think we're going to see a lot about how we can make checkpoint inhibitors work better whether it's adding <unk> four blockade, adding CD 28, I think there is theres a lot of promise, but with still a high unmet need.
Yeah, I would just add Scott is correct I think prostate cancer is the landscape is shifting very quickly with the state in 2008 data.
Specifically the keynote 191 data I don't think it impacts us maybe it gives us a little bit more breathing room remember.
Both Merck and BMS decided to move forward with their PD ones.
In combination with Docetaxel for phase III, and we have the first read out the.
The interesting issue is that for PD, one clearly keytruda had a low response rate and it appeared that the BMS data with Nemo <unk> seem to be higher and Thats. Why we were excited about using our PD, one <unk> four who to allomap.
We were later to the game to them and they have already started their phase III with Docetaxel and so therefore, we tried to sort of do something that would be going to where the puck is not where the puck will be and not where the bucket and so we tried to do a little bit more aggressive in terms of our chemo regimen.
So I think the fact that the Docetaxel didn't work for them gives us some more opportunity if that option is there, but I think <unk> hit the nail on the head there is a lot of things changing in prostate cancer.
Yes.
Yes, thanks for the color and insight there that's really helpful. And then just another quick one.
For me if I may.
Just how does the new partnership with Caris aid your target discovery behind beyond your own in house capabilities and do you have any specific targets in mind for the the.
The partnership.
Yes, I mean, the simple answer is we don't have a lot of in house capabilities, I mean, thats, a pretty specialized capability that <unk> brought to the table and thats something that we would rather spend our resources, making best in class modalities to address these kinds of targets, but we have other ways of trying to access other Todd.
And also remind you we have our a trick of collaboration which again gives us access to novel class of targets, Yes, and I would just add as being a corporate clinic familiar with caris <unk> clinical data and remember they have mountains in decades worth of tumor samples that they've collected from patients. So I think that's a huge differentiator we're good at making antibodies.
But we do not have the sample database.
The tumor databases that they have.
Great. Thanks for taking my questions.
Thank you.
Our next question comes from David Nearing Garden with Wedbush. Your line is now open.
Hey, Thanks for taking the question.
Been asked but maybe a follow up on <unk> III toxicity question.
Macrogenics also in that study combined that with various Io agents.
And I was just wondering if that was a concern or potential cause of the added toxicity.
I don't know, bringing in immune cells to vasculature, that's targeted by be sort of an H three or something like that but I was just wondering if you could.
Any insights or preclinical.
Preclinical assays or anything that.
So caution on different Io agents plus <unk>.
<unk> targeted agents.
No I can't say, we've had anything we gave the RMB 780, <unk> 28, which of course isn't immune target CD 28 at very high doses in our nonhuman Primate Tox studies with no fat no <unk>.
So we don't have any more answers on that data then.
Earlier I do note that that is an antibody a lease of an <unk> antibody that is.
Immune.
FC Gamma receptor.
The antibody and so it would be expected to have to address that toxicity Avi seven HC bearing cells.
Sure.
Could that be playing a role possibly.
Yes, I mean every every modality is different so it's.
Really hard to predict but the other thing I'll add is that our molecule is a two plus one that was specifically designed to be more selective for binding to tumor cells, which generally have a lot brighter b <unk> expression. So.
There could be other points of differentiation that will that will help us on the safety side.
Okay.
Great. Thanks.
Thank you.
Our next question comes from Bill Maughan with Canaccord Genuity. Your line is now open.
Hi, Thanks for taking the question.
Looking forward to is Booz Allen that I've read out is there are there any specific cohorts that you think are more or less key to the success of the program whether that's due to.
Read through for Dow on that mechanism of action being most appropriate for these patients or <unk>.
Commercial.
Is there any specific cohorts that you think are more or less key to the success of the program whether that's due to.
Read through for <unk> mechanism of action being most appropriate for these patients or <unk>.
Commercial.
Unmet need for a specific cohort.
Okay.
We think that is that again, it's not really going to be that different in terms of the potential or the insights on the readout from the different cohorts.
Hemo, receiving patients certainly the PARP inhibitor, receiving patients doesn't have DNA damage.
Repair deficiencies are sort of a separate category.
So no. It really is again those all those cohorts together the great majority of patients getting chemo.
Okay.
I can help with <unk>.
On safety and on.
Activity. So initially from very small patients right as it gives us first direction.
So I don't think theres going to be that much insight gleaned on a narrowing of the program at this early stage.
Okay, and then on the 104 data from <unk> beyond just the efficacy and safety on the poster.
Were you able to green anything on Biomarkers, whether it would be.
Expression levels or T cell.
Proportions of different populations that might make a patient more or less likely to respond.
Not really not really.
Was very cleanly, well tolerated molecule and we saw activity in different tumor types.
Laurence sustained.
Stable disease for multiple years, even but no biomarkers that really popped up the correlated clearly there's much of anything we are trying a biomarker driven hypothesis in our expansion cohorts combining of the Pollinium AD, which is known historically to up regulate iqos.
Okay and last one sorry, if I missed this or dropped briefly but.
Can you give detail on the on what drove the increase in.
<unk> guidance for your cash balance at the end of the year.
John do you want to hop on and take that.
Yes sure.
Good update.
Guidance as you pointed out it actually increased.
To have between $5 $55 million to $75 million.
As of 12 31 based on current plans.
Yes.
With runway through the end of 2025.
Okay and can you can you is there anything explicitly that drove that update.
Primarily I think the.
The royalty revenue from <unk>, we didn't have a lot of clarity into the actual timing and the dollar amounts of that so it's been a little bit higher than we expected.
Okay. Thank you.
Thank you and I'm currently showing no further questions at this time I'd like to turn the call back over to <unk> for closing remarks.
Soon and have a wonderful evening everybody for joining us today, and we look forward to updating you again soon and have a wonderful evening.
Okay.
This concludes today's conference call. Thank you for participating you may now disconnect.
The conference will begin shortly to raise Johan during Q&A you can dial one one.
[music].
Okay.
Sure.
[music].
Okay.
Okay.
Okay.
Okay.
[music].
[music].