Q4 2020 Jounce Therapeutics Inc Earnings Call
Good morning, ladies and gentlemen, and welcome to the Jounce Therapeutics fourth quarter and full year 2020 earnings conference call. At this time all participants are in a listen only mode. Later, we will conduct a question and answer session and <unk>.
From this will follow at that time as a reminder of this conference is being recorded at the company's request I would now turn the call over to your host.
Now on.
E on with Jounce Therapeutics. Please go ahead.
Thank you operator, good morning, and welcome to the Johnson Therapeutics, Inc, fourth quarter and full year 2020 financial results Conference call.
This morning, we issued a press release, which outlines the topics that we plan to discuss today. The release is available in the investors and media section of our website at Www Dot Jounce, TX Dot com.
Speaking on today's call will be our CEO and president Dr. Rich Murray, who will discuss our pipeline progress on key milestones for 2021, followed.
Followed by our CMO, Dr. Beth <unk>, who will provide an update on our clinical activities and lastly, our CFO Kim Drapkin will review, our full year 2020 financial results and 2021 guidance. We will then open the call for your questions.
Before we begin I would like to remind everyone that today's discussion will include statements about our future expectations plans and prospects that constitute forward looking statements for the purposes of the safe Harbor provision.
Under the private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including the risk factors discussed in our SEC filings.
In addition, any forward looking statements represent our views only as of today February of 'twenty, five 'twenty 'twenty, one and should not be relied upon as representing our views as of any subsequent date, while we may elect to update these forward looking statements at some point in the future, we specifically disclaim any obligation to do so.
Even if our views change with that I will now turn the call over to rich.
Thanks, Melanie and good morning, everyone.
As we reflect on 2020.
To note the meaningful progress Jounce is made to advance our growing discovery and development pipeline to align directly with the needs of cancer patients.
Our new potential first in class programs and biomarker approaches are aimed at both PD, one inhibitor naive patients as well as the growing PD one inhibitor experienced population.
With two proof of concept studies actively enrolling patients that's the.
Stable and robust discovery effort validated via an important to out license to a partner and a strong balance sheet.
We are entering 2021 with the potential to make significant positive impact on the lives of cancer patients.
One of the 20, you saw the achievement of the important clinical execution milestones for our highest priority program Gtx 80 64.
RB two <unk> also known as <unk> four inhibitor.
As well as for both the telematics.
The <unk> agonists.
In January we announced that enrollment commenced and the need of our phase one Gtx 80, 64 clinical trial.
The new trial is designed to move quickly through the necessary dose escalation portion of the trial, leading directly to the opening of multiple tumor specific expansion cohorts in the second half of the year.
These expansion cohorts will include both Gtx 80, 64 of monotherapy as well as combination therapy with our own PD, one inhibitor gtx $4 14.
In October 2020, we began enrolling biomarker selected patients in select <unk>.
Phase II proof of concept study of both the kill them that.
Also in combination with our PD, one inhibitor Gtx 40 of 14.
Not only will the select trial test the impact of broker.
We will also gain additional important single agent data for Gtx, $4 14, and the new biomarker selection paradigm.
We believe the tests broker of biomarker will select more appropriate patients for both the CVA mediated benefit of a PD one inhibitor as.
As well as for the potential so the four related benefit for Gopro.
In addition in October 2020.
We license the Gilead the worldwide rights to Gtx 18 of 11.
The potential first in class antibody designed to selectively deplete immuno suppressive tumor infiltrating T regulatory cells.
We continue to progress Gtx 18 of 11, two R&D clearance and we are on track for R&D. Finally in the first half of 2021.
On clearance of the IND Gtx 18 of 11 will transfer to Gilead for clinical development and potential commercialization.
In addition to the $85 million upfront and 35 million equity investment.
Jounce has the potential to earn up to $685 million in milestones as well as royalties on worldwide sales.
Although our primary goal is to retain and develop our wholly owned Jounce discovery programs. In this instance, we felt an out license was the right deal at the right time.
It's given us the financial flexibility to fund our two proof of concept studies and further progress our translational discovery engine and bring new candidates forward.
As we look to 2021, the significant unmet need faced by many cancer patients continues to be at the forefront of everything we do.
That will take you through more details on our two POC studies of Nate and select in a moment.
Before turning the call over to her.
Like to take this opportunity to reflect on what we believe it will take to bring meaningful and long lasting benefits to cancer patients.
As PD, one inhibitors expand into earlier lines of therapy, including non metastatic settings.
<unk> of the PD, one inhibitor resistant market continues to grow.
Unfortunately, most patients receiving of T cell checkpoint inhibitor as their first Io therapy will not benefit.
Highlighting the need for new treatment options.
We continue to believe that new mechanisms targeting different immune cells in the tumor microenvironment will be required to derive meaningful clinical benefit and the growing population of patients with PD, one inhibitor resistant tumors.
The need for novel approaches highlights the importance of our translational science platform and our productive sustainable discovery engine, which has allowed us to generate targets beyond T cells.
Most of the most notably J T X 80 64.
Gtx day to 64 aims to convert immunosuppressive macrophages to an anti tumor state.
To create a bridge between the unique and adaptive immune systems.
This is something T cell checkpoint inhibitors cannot do alone.
And it May result in the potential to reverse PD one inhibitor resistance.
More broadly beyond Gtx 80, 64, our discovery efforts are aimed at additional members of the <unk> family of receptors as part of the dedicated strategy around the myeloid based cells of the immune system.
Beyond the low receptor family, we remain committed to addressing the needs of cancer patients through our early stage discovery programs are.
Our discovery engine is built upon the capability to thoroughly investigate different cell types in the tumor microenvironment.
In addition to myeloid cells, we believe stromal cells are another important target with the potential to modify this environment and allow the immune system to become fully operational on the tumor.
Jounce has stayed true to its initial scientific mission of investigation discovery and development of therapies that target different cell types in the tumor microenvironment.
Aided by a biomarker approach with the.
The aim of the enabling the immune system to fight tumors.
We believe this approach will be necessary to reach new levels of therapeutic benefit generated by the immune system.
I'd like to take a moment now to welcome the newest member of our board of directors.
Dr Luisa Salter Cid.
Who was appointed earlier this month.
Dr. Salter said, we'll further expand Jonathan immunology, and the Io expertise and we look forward to her valuable contributions.
With that I'll turn the call over to Beth to discuss of our clinical pipeline and science and where the shale.
Thanks, Rich and good morning, everyone.
We made great progress at Jounce in 2020, and I'm very proud of the work our team has done to enable us to execute on our two ongoing proof of concept studies of Nate and select.
These programs are key to our belief that novel mechanisms and biomarker strategies are necessary to bring clinical benefit to patients who do not optimally benefit from T cell checkpoint inhibitors.
As rich mentioned, our pipeline is well poised to address the significant unmet medical need of patients with tumors that are either sensitive or resistant to PD one inhibitors.
I would now like to provide more detail about our ongoing clinical trials, beginning with our highest priority program J T X 80 64.
Which is designed to reprogram immunosuppressive or M. Two macrophages to immune stimulatory or M. One macrophages in order to enhance or restore anti tumor immune activity.
The mechanism of action is very different from other macrophage targeting therapies, such as <unk> inhibition of CSF, one are to deprive the myeloid lineage of the key growth factor and see the 47 to improve macrophage mediated phagocytosis of tumor cells.
<unk> 8064 is the Lille RB two antagonist antibody, which we view as the macrophage checkpoint inhibitor with the potential to reverse PD one inhibitor resistance.
The primary like end of <unk> are HLA molecules, which are critical in the recognition of cell by the immune system, preventing our immune cells from destroying our own normal tissues.
When Lil RB two binds to its like in which include HLA G on tumor cells and HLA E N feet on immune cells. It induces an immunosuppressive state similar to the effect of PD, one binding to PD L. One.
In preclinical studies J T X 80, 64 interferes with the binding of Miller of <unk> to its ligand, resulting in an immune stimulatory state with production of pro inflammatory cytokines improved antigen presentation and T cell activation.
<unk> is expressed on cells in the innate immune system, such as an expectation.
We have evidence of the direct macrophage M to M. One conversion from in vitro studies in which J T X 80, 64, REIT programs. The cytokine production of macrophages from immunosuppressive cytokines, such as IL 10, two immune stimulatory cytokines such.
<unk> TNF alpha.
In addition, when J T X 80, 64 blocks of the binding of <unk> to HLA <unk> and HLA B on the macrophage itself. These critical parts of the antigen presenting machinery of the cell are now able to function again, resulting in improved antigen presentation.
<unk> and T cell activation.
<unk> is not expressed on T cells, which are members of the adaptive immune system.
We have shown the J T X 80, 60 for treatment of <unk>.
Cells derived from both peripheral blood and human tumors ex vivo results in T cell activation, providing evidence of J P. X 80, 60 fours ability to create a bridge between the innate and adaptive immune system.
This biology, along with recently reported initial clinical data on another little RB two inhibitor.
Just the potential for J T X 80, 64 in combination with PD, one inhibitors to reverse PD, one inhibitor of resistance as well as to further improve outcomes in PD, one inhibitor sensitive tumors.
By having the potential to provide clinical benefit to a wide range of cancer patients.
At the start of this year, we began enrollment in the of Nate Phase one clinical trial of Gtx 80, 64 alone and in combination with our own PD, one inhibitor J T X 40, <unk> thousand 14.
Our trial is designed to progress quickly through dose escalation and demonstrate proof of concept in tumor specific expansion cohorts.
The expansion cohorts will address multiple different patient populations to identify the best and most rapid development path for J T X $80 64.
Indications will be selected based on a variety of factors, including biology, RNA signatures and the opportunity for differentiated development pathways.
Additionally, an important part of our indication selection process involves an examination of the unmet needs and opportunities across three major IOC segments.
The first group is patients who are PD, one inhibitor experienced whose tumors are now PD one inhibitor resistance.
This represents a large and growing area of unmet need in which a drug that reverses PD one inhibitor resistance could make a great difference for patients since chemotherapy is the predominant and not very effective standard of care.
Importantly for Jounce, there are no approved PD, one or PDL one inhibitors in this patient population, giving us the opportunity to develop two wholly owned Jounce product J T X $80 64, and J T X 40, <unk> as a combination approach.
The second group is PD, one inhibitor naive patients who have tumors for which there are no PD, one or PDL, one inhibitors approved because they generally have not demonstrated much efficacy.
It's J T X 864 can reverse this type of primary resistance.
Combination with the PD, one inhibitor could make immunotherapy of therapeutic option in this area of high unmet need.
This also represents an opportunity for Gtx 1064, plus J T X 40, <unk> 14 due to.
The lack of approved PD one inhibitors.
The third group is PD, one inhibitor naive patients who have tumors for which there are approved PD, one or PDL, one inhibitors, where some patients achieved durable clinical benefit, but there is still much room for improvement.
Developing gtx $80 64 in this setting would give us the opportunity to treat frontline patients in combination with PD one inhibitors.
We plan to include all three groups of patients in our expansion cohorts as we explore the best opportunity for J T X 80, 64 to make a difference.
With cancer.
As part of the trial, we will also be collecting data on the number of different pharmacodynamic and potential predictive biomarkers.
The findings will help US guide further development and are an important part of justice philosophy of providing the right immunotherapies for the right patients.
As the enrollment in the Nic continues we will begin to guide on the timing of data Readouts. We are pleased with the progress of the trial and completed enrollment in the first dose cohort in January.
We also plan to present preclinical data on Gtx 80, 64 at multiple scientific meetings this year.
I would now like to turn to an update on both <unk> and our first biomarker patient selection trial select the so.
Electric trial, which we initiated in October 2020 is currently enrolling approximately 75 immunotherapy nave second line non small cell lung cancer patients.
Who will be selected using the predictive pittsfield for biomarker and randomized to Bopara plus our PD one inhibitor J T X 40, <unk> 14 versus <unk> 42014 alone.
His copra is an 18 gene signature that includes genes relevant to both CD eight and CD four T cell biology, and has been optimized to predict or emergence of Iqos high CD four T cells in the peripheral blood.
Which have been associated with clinical benefit in patients treated with bopara plus or minus the goal about.
We expected approximately 20% of second line non small cell lung cancer patients to be typical for positive and we are pleased that screening to date has validated this projection.
We are continuing to screen and enroll patients and select but we are experiencing COVID-19 related delays that are impacting patient enrollment.
Given the challenges we are facing we now anticipate reporting data from the select trial in 2022.
As rich mentioned 2021 is an important year of execution and key milestones for Jounce building on our team's key accomplishments in 2020.
We would not be where we are today without the dedication of our team our valued investigators and most importantly, the patients who put their trust in our drugs to make a difference in their lives.
We look forward to continued progress in 2021, as we focus on trial enrollment and collection of high quality clinical and biomarker data to guide our programs.
Now I would like to turn the call over to Kim for a discussion of our year end financial results Kim.
Thanks, Beth and good morning, everyone.
As we reported in this morning's press release, we ended 2020 with cash cash equivalents on investments totaling $213 2 million compared to $174 million for 2019.
The increase was primarily due to the receipt of $120 million of proceeds from the license and stock purchase agreements with Gilead and $14 5 million received during 2020 under our ATM program offset by operating expenses incurred during the year.
Turning to the P&L, our license and collaboration revenue was $62 3 million for full year 2020, compared to $147 9 million for 2019.
Revenue recognized during 2020 was related to our license agreement with Gilead.
Revenue recognized during 2019 was related to a license fee and collaboration revenue under our former Celgene license and collaboration agreement.
During 2020, we recorded $78 7 million in research and development expenses compared to $67 1 million for 2019.
The increase in R&D expenses was primarily due to $7 9 million of increased clinical and regulatory expense primarily attributable to the select clinical trial $3 2 million of increased manufacturing and IND, enabling expenses and $2 9 million of increased employee compensation costs.
These increases were partially offset by decreased travel and lab consumable costs.
General and administrative expenses were $28 8 million for 2020 compared to $27 9 million for 2019.
The increase in G&A expenses is primarily the result of increased employee compensation costs.
Net loss for 2020 was $43 8 million or basic and diluted net loss per share of $1 24, as compared to a net income of $56 8 million in 2019 or basic net income per share of $1 72.
Diluted net income per share of $1 66.
Net loss for the full year 2020 was attributable to increased operating expenses offset by $62 3 million of license revenue recognized under our agreement with Gilead.
Net income for the full year 2019 was primarily attributable to a $147 9 million of revenue recognized under the Celgene license and collaboration agreements in the year.
In 2020 and January 21, we sold a total of approximately five 2 million shares resulting in net proceeds of $44 7 million under our ATM offering.
<unk> sales were primarily block trades, the biotechnology investor and resulted in the completion of the existing ATM.
We reiterate our 2021 financial guidance, we provided in January.
We continue to expect gross cash burn on operating expenses and capital expenditures for the full year 2021 to be approximately $95 million to $110 million.
Given the strength of our balance sheet, we expect our existing cash cash equivalents and investments, including the additional $30 2 million in funds received in January 2021, under our ATM program to be sufficient to enable the funding of our operating expenses and capital expenditure requirements through.
Q2, 2023. Additionally.
Additionally, we continue to have the flexibility to drive our innovative immunotherapy pipeline, while efficiently executing against our strategic plans and goals.
With that I'll hand, the call from rich for a final thought.
Thanks, Kim on the <unk>.
Sales of the strong 2020 of pipeline execution and corporate development.
We're poised for an important year with the following key milestones.
Established safety and recommended phase two dose for <unk> 864, then open tumor specific expansion cohorts in the second half of 2021.
Continue enrollment to enable reporting of preliminary efficacy and related biomarker data for <unk> from J P. X 40, <unk> 14 from the select trial in 2022.
Continue R&D of neighboring activities for Gtx 18 of 11 and anticipate an IND clearance from 2021.
<unk> continued to advance our discovery pipeline of firm.
First in class programs with the goal of the new IMD every 12 to 18 months.
We look forward to updating you on our progress throughout the year.
Before I close I'd like to take this opportunity the thank the investigators and Johnson employees, who despite the challenges we all face during the COVID-19 pandemic remain dedicated to our mission of bringing new therapies and benefits of cancer patients.
And most importantly, we extend our thanks to the patients who have had the privilege to treat.
With that we'd now like to open the call for your questions operator.
Thank you as a reminder to ask the question you'll need the press star one on telephone to withdraw your question. Please press the balance sheet.
Please standby, while we compile the Q&A roster.
Our first question comes from border Speaker with Cowen You May proceed with your question.
Good morning.
So on my first question is on $80 64, I'm, just curious have you compared it to merck's drug in preclinical development and if yes. What are the differences that you observed between yours and merck's drug.
Hi, Boris Good morning, Yes, I will take that one this is rich.
Yes, we have compared it in the following way we posted data.
And in various presentations.
Our debt we've been at Merck has done that as well so comparing those two different kind of releases of data from each each company respectively.
864 is very taken very specific inhibitor of <unk>.
Low RB two <unk> based on the existing data that we can compare it in this way.
We see similar properties, we believe that kind of leads to the potential of read through from.
From the from the Merck data releases and importantly, we view kind of of the potential of kind of differentiation as we move forward. That's something of course, we pay attention to but like PD, one PD one approval landscape.
We see many many opportunities that are really dictated by clinical strategy and of course of our biomarker implementation in the future as well.
Great and my second question is obviously you are in dose escalation phase right now I'm just curious based on your preclinical work.
When do you anticipate to get to a therapeutically minimal effective dose.
The current rate.
Hi, Boris this is Beth I'll take that one.
I think what we've what we've said to date is the the studies designed to move as quickly as possible to those to getting to us of potentially therapeutic dose and expansion of the tumor specific cohorts, which are designed to demonstrate proof of concept and.
So.
If you think about of typical phase one trials, sometimes it can take a year or even a year and a half to get to that point, whereas we started enrollment and actually completed enrollment in the first dose cohort in January and we are expecting and on track to open the expansion cohorts in the second half of this year.
So I think.
That would say within six months from now we expect to be at a dose that we think is potentially therapeutics and that's when we would open expansion cohorts.
Great. Thank you very much for taking my questions.
Youre welcome.
Thank you. Our next question comes from of Michaels of Baird. You May proceed with your question.
Hi, guys. Thanks for taking the question maybe I could ask another one on the 864.
And maybe a bit of a follow up to <unk> question here just for the dose escalation, obviously, you're through the first cohort.
If you can comment, but how many cohorts are you anticipating testing.
Yeah, I think rather than getting into the specifics of the number of cohorts of all of.
Just reiterate we expect to be true dose escalation and into our expansion cohorts by the second half of the year.
And will that just be for the mono therapy or will that be for both the monotherapy and the combination expansion, yes. It will be yeah, we'll be initiating the cohorts for both monotherapy and combination in the second half of the year.
Got you and then maybe just the last quick.
Quick question from me.
You seem.
Pretty confident that you'll you'll be in that position in the second half and I guess.
Just given what's happening with select and Covid is having some impact there and delaying things is there any risk of those those timelines at this point or what youre seeing as well.
Gives you enough confidence that you can hit the timeline. Thanks.
Yeah, that's a great question Mike.
We are not currently experiencing any COVID-19 related delays for of Nate.
You're right, though there's a lot of uncertainty.
We think we'll encounter delays, we'll let you know, but we believe with.
The number of sites the enthusiasm of the investigators and the way that the trials going so far at this point, we felt comfortable saying that will be in those expansion cohorts of the second part of the year.
Great. Thank you.
Thank you. Our next question comes from Mark Theres easily the HC Wainwright you May proceed with your question.
Good morning, everyone. Thanks for taking my question here is off of for Archie. So I have two questions. One is regarding the <unk>.
<unk> 64.
Just wondering if you guys could give us more color on the tumor type selection for the.
The red tumor specific cohorts or we kind of still waiting for the data from the gross exited escalation study and.
The second question regarding the 18 of 11.
RMB of fighting to one other.
Preparing your guys' required to before the volume.
Thanks.
Okay. So this is beth on the indications for our Nate we will identify the tumor types that we've selected and the scientific rationale behind them mid year. This year at either of company sponsored event, such as an R&D day or at a medical meeting.
<unk>.
Yes, I can take I can take the question for 18 of 11.
Yes, so we're in the kind of typical stretch of where we are in the IND.
<unk>, enabling process for monoclonal antibodies, where.
The focus really is on ensuring the supply is produced.
<unk> generated appropriately.
All of the analytical data using shapes, and then compiling that into into ultimately into the IND.
As is typical for an antibody that's usually the the rate limiting factor.
Yes, we're comfortable with with where we are that's going well.
We're engaging with our colleagues at Gilead as we look to as we look to transfer of that program.
And maybe I can just add debt you know another.
Important part of the I N D is the clinical protocol.
And we're working very closely with gilead on that and that's going very well.
Thank you. Thank you very much.
Thank you and as a reminder to ask a question you will need to press star one on your telephone. Our next question comes from Steve <unk> with Raymond James You May proceed with your question.
Hi, Good morning, a couple of questions about 864, just on the biomarker.
<unk>.
Would this be something.
Would you anticipate the as being something as simple as just looking at HLA expression like <unk> expression or even low RB two expression.
Or are you thinking this will be like a pistol the oprah like RNA signature.
Maybe if you could just talk about sort of what types of biomarkers, you're exploring in the relatedly.
Do you know if if each of LNG are low every two or over expressed in PD one resistant.
Patients that I have a quick follow up thanks.
Sure so in.
In terms of the the Biomarkers that we're exploring as potential predictive biomarkers.
Many of those were in the poster that we presented at Citi 2020, and they and we were very pleased to see how well they correlated with the biology, so little RB two as one HLA a and B were included and also our proprietary tumor.
Tumor associated macrophage signature. So for this first study we will be exploring of broad panel of both gene signatures and also immuno histochemistry biomarkers.
And once we sort of see how that plays out.
In terms of relationships with clinical data.
That will help us to narrow down onto the predictive biomarkers that we think will be the best for the program. So I think we're in a we're in great shape, we have a number of different ones to test and we'll be testing them retrospectively. In this first study, but always with an eye to being able to identify something that we could test prospectively.
Going forward.
With respect to I'm, sorry, I've forgotten your second question.
Just do you know if the IHG based biomarkers that you're including in the the exploration are they over expressed on PD one resistant tumor.
Tumors.
Well one thing we know is the one of the mechanisms of PD. One inhibitor resistance is lack of loss of HLA.
Heterocycle City, and also and lots of data to micro globulin inability to present the antigen. So we think that blue arc that I'm, a little RB two inhibitors, such as <unk> 64 could help to address some of that I'll, let rich add more on that.
Yeah, Yeah, so some of that.
If it's a good question and we're really zeroing in on that but some of the answers to that stay tuned to the presentations that debt was alluding to the scientific presentations, we will have a lot more on biomarker data characterization of different.
Different patient populations that we hope.
And in and out.
The company meetings.
Okay, great. Thanks, Richard.
Heard from Beth and then the last question I. Just had is can you remind us if.
As we think about your little RB two and other Iot family member of inhibitors, and the sort of emerging competitive landscape I was hoping you could remind us are there any modifications or engineering to your antibody.
That are necessary to diminish or eliminate BDC fee and is that a feature of the difference between some of these competitive antibodies is irrelevant because the necessary if.
If you could just comment on that would be great sure sure. So I think I think the general.
The general emergence of these programs, we think theyre likely to kind of continue.
Is that the.
The FCS will be disabled are minimized.
Because really the for solid tumors, because some of the biology is really heading towards straight up antagonism, we want to keep that receptor from binding from its ligand.
The differing strategies will really be a completely different road to travel where there is potential in some heme malignancies, where you may want to invoke some tumor cell specific.
Targeting the that's not the way our molecule is built our molecule is built in a way that's similar to the design of of Mark as far as we know.
Which is an atg four so we've minimized the effector function.
And so the kind of engineering that we foresee in the future as additional mono specific agents that are being brought forward that are highly selective to the different receptor families. The.
The concept the potential of.
The Biospecifics and of course, the the kind of of the combination strategies that one would put into a clinical trial design.
Very helpful. Thank you.
Thank you. Our next question comes from Jay Good jaw with Roth Capital Partners. You May proceed with your question.
Good morning, guys. Thanks for the update just have a question on.
On several of the different things you mentioned that this morning. So the first is about the opera I know youre not going on have gone up this year, but GSK debt mentioned that they should have gone up from their program by midyear or so just kind of wanted to know.
How much read through should investors kind of takes on whats happening with GSK is there any difference between the client shifts or anything like that that should be accounted for.
Yeah.
Ill, let rich address the differences between the molecules and that I can say a few words about the clinical strategy.
Sure, Yes, I think there's a couple of low levels of that if we just look at the at the antibodies itself.
Hum.
We went with our preclinical data in terms of choosing our antibody the binding sites the <unk>.
And we chose.
Agg, one as our FC and that was explicitly chosen because.
I think everyone recognizes gives you better signaling for an agonist antibody so that IGD one backbone is in our opinion the way to go for for agonist activity.
We've subsequently proven of course and Derisked.
From our clinical data is that that is associated with any cell depletion that just simply doesn't occur we publish that many many times the.
So that's the difference.
IGD, one in ours versus <unk> in.
And Gsk's.
We also believe just through kind of comparing datasets preclinical data that the binding sites, maybe maybe a bit different as well.
So our molecule. We believe is a very highly potent engineered appropriately.
Just to take to take forward so just from a comparative.
Standpoint, the molecules between GSK and Jounce for the Iqos agonists.
Or have some have some differences anywhere from nuances from two things that could be more meaningful.
I'm going to let Beth talk about the kind of the Biomarkers and the clinical strategy and how we see that part of what could be what could be read through.
Sure. So the data that we would expect them to be presenting this year would be.
In PD, one experienced non small cell lung cancer in combination with a PD one inhibitor. So very different from the trial that we did in PD, one experienced non small cell lung cancer and then they're also going to be we think announcing whether their phase two three trial in <unk>.
<unk> had net cancer will reach its gating criteria to move forward. So we look forward to seeing their data, but I think for us we're using.
The biomarker selection strategy and our frontline I'm, sorry, not frontline, but PD, one inhibitor naive non small cell lung cancer study.
And we're currently not studying had net cancer so.
I think there are some similarities it's obviously targeting the same thing it's an agonist, but we've also taken a different approach with a biomarker and.
And potentially also different dosing strategy. So there are enough differences that it's a little hard it's not like them.
What we've talked about with Mark 48, 30 of J T X 80, 60 for where we think there's more similarities than differences there may be some differences between our Iqos program of Gsk's.
Yes, maybe I can help the I'll just jump on to one more one more point there that is a little bit of I think learnings along the way here across across immunotherapy not just jounce is that.
As you go after those kind of T cell T cell mechanism combos, we really think the of the Io naive PD one naive patient populations are the way to go in our biomarker strategy is really looking to pull together of the patients that we think are most appropriate for both the PD one effect is.
Well as the the effect of a vote from which we can measure through its pharmacodynamic activity in relationship to benefit.
I think our kind of biomarker strategy as Ben alluded to which is also very kind of distinguishing for us. We think in that kind of space you really really want to find the right patients with the kind of multiple T cell T cell mechanisms.
Thanks, Rich and then just the follow up on 80 64 of any comments on why enrollment might be gone so well and then you know.
Are we likely to see any kind of data from the nice apparently on before the end of the year.
Sure so.
We've worked with great investigators, we spend a lot of time talking about the science of the program and I think they really believe in this mechanism. So also patients are always looking forward to opportunities for novel Io therapy.
As I said, we're very pleased without things are going to date.
We've traditionally been able to enroll our phase one clinical trials pretty quickly I think for those reasons. We worked very closely with the sites with the very hands on approach.
In terms of data.
So we will provide guidance in the second half of the year. Once we've opened the expansion cohorts on when you can expect to see data.
Thank you and then actually just kind of moving to the next to the first one is about 18 of 11, just kind of wanted to know if you're going to get any kind of milestone payment might be trans net over the A&D.
On to Gilead and then a follow up to that is just also you know how much leeway you have in terms of.
Data updates on that program on is just about a week on interest being driven by I can be at that point and then lastly, Mitch you talked extensively about the the quick math of pipelines have just on wanted to know.
Are you done of nominate anything from the program from the pie.
This line.
And then if you line is going to be one of the myeloid Stonewall targeted agents and then.
Net debt is quite low but also you talked a lot about you know targeting you know different different cell types of I'm. Just wondering again you know are you guys going to explore additional combinations beyond the the PD, one combos and things like that.
Sure Zach but thanks for your question. This is Tim I'll start on the Gilead and then I'll hand, it over to rich and he can give you some more information on your discovery related questions.
So in terms of the Gilead milestones, we're not at Liberty to disclose when and if we'll achieve any milestones, but importantly, the $685 million of milestones that we have the opportunity to earn $510 million of those our development and regulatory so we were happy with the negotiation of that and the.
<unk> to earn milestones in the more near term as opposed to being on.
Completely back loaded.
And just keep in mind, all the all of our financial projections like our cash going through Q2 2023 do not include on the earning of any milestones that would extend our runway even further and when and if we earn a milestone we will announce it at that time.
And I'll turn it off of a rich for your other questions.
Sure, Yes, so I.
I may have missed missed the question, but you asked about new new candidates and yes, we're very excited about how things are on.
Things are going in discovery.
We are quite active in kind of the myeloid related space. So macrophages low RB two <unk> <unk> thousand 64.
There are other family members of the <unk> family debt invoke.
The more dendritic cell biology of NK cell biology.
We really think that.
You don't kind of optimizing the therapeutic benefit from these different myeloid cell types.
Is something that.
It's something that.
<unk> fits well with then combo with a PD one inhibitor so.
Kind of some of the lead discovery programs are kind of in and around that space.
Stromal biology, we think is kind of a next wave.
As well, so I'd, rather not pinpoint the specific molecule at this point.
The the.
Usually when we get to kind of a development candidate, which is a meeting of certain criteria for US is when we announced that and you know we're on we're on track to we're on track to do that.
Okay.
I may have missed the EMEA of Mr question.
I think the loss of any kind of hit on many of which is condos beyond <unk>.
One thing about you know maybe combining some of you at the age of in your pipeline.
Yeah. This is Beth I can comment on that so.
You know I think as you know were really driven by the biology and really focus on rational combinations. So this is definitely an area. We're continuing to explore from J T X 80 64.
As we've spoken about macrophage rich tumors are of interest for us and there are published data showing the macrophage infiltration may increase after some chemotherapies or radiation therapies. So we're continuing to explore.
The breadth of combo opportunities for J T X 80, 64, because we really think it's the a program with a lot of potential to make a difference for patients.
Thanks for the update guys.
Yes.
Thank you ladies and gentlemen, thank you for participating in today's conference. This does conclude the program you may now disconnect have a good day.
[music].
Okay.