Q3 2019 Earnings Call
Good morning, ladies and gentlemen, and welcome to the Jones Therapeutics third quarter 2019 earnings Conference call.
At this time, all participants Oh listen only mode.
They do we will conduct a question answer session and instructions will follow at that time.
As a reminder, Minder. This conference is being recorded at the company's request I.
Ill now turn the call over to your host almost Joshi with Jones Therapeutics. Please go ahead.
Good morning, and thank you for joining us for our third quarter 2019 financial results Conference call. This morning, we issued a press release, which outlines the topics that we plan to discuss today the releases available in the investors immediate 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 provide an update on our pipeline progress and corporate development, followed by our CMO Dr. best trade, who who will provide an update on our clinical activities and lastly, our CFO Kim Drapkin will review, our third quarter financial results and provide and.
Update of our 2019 guidance.
We will then open the call for your question.
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 statement for the purposes of the safe Harbor provisions 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 as E filing.
In addition, any forward looking statements represent our views only as of today November 7th 2019, 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, Caramel and good morning, everyone.
The Johns team has continued to work diligently on advancing our pipeline in executing on our strategy of developing immunotherapies with the potential to provide long lasting benefits cancer patients.
Specifically, we are pleased to report the continued progress of our two clinical stage programs well for telematics Oprah or I costs agonists, Andrew do you at 44 team our PD one inhibitor.
As well as the further development of our discovery pipeline.
The cornerstone of the vote preclinical development program is I goes high Cdfour T effector cells evoke associated Pharmacodynamic biomarker, which has not seen with PD one inhibitors.
Earlier this year, we presented exciting data from the iconic study our phase one to vote brought clinical trial at eight you see are showing improved responses PFS and always directly linked to the emergence of these cells.
Based on extensive reversed translational analysis from our iconic trial presented at several scientific meetings, we've identified two development paths for the vote for program.
In the first development path, we're focused on fully realizing the biology.
It goes high Cdfour T cells.
Both the induction of the cell population as well as their expansion and sustained activation.
To date, the vast majority of Io approaches attempt to enhance C. D E T cells.
However, fundamental immunology reinforces the importance of Cdfour T cells, there states of specialization and their central role in orchestrating immune responses.
Based on this biology, we initiated the phase two emerged trial in mid June applying a unique dosing and sequencing schedule of the Volpara candidate for women Bob <unk> combination.
In the second development path will focus on the use of a predictive biomarker.
And the analysis of iconic patience, we were able to identify a biomarker from baseline samples that correlated with the emergence of the I can fight Cdfour T cells response rate PFS, and OS and patients treated with volpara alone or in combination with nivolumab or nivo.
We plan to use this potential predictive biomarker to select patients in a new trial with Volpara and our own PD, one inhibitor Gtx 40 14.
We will provide more details in the next few months on this clinical trial.
At the annual synergy conference on Saturday November 9th we will present the emerged trial in progress poster.
The poster will include the scientific rationale for the trial and the combination dosing and sequencing strategy.
We believe our strategy Optimizes, both the kinetics of the induction of Ipos high Cdfour T effector cells by Hippy.
And their expansion and sustained activation by Barbara.
We spent considerable time with our founders to develop the strategy.
With our wholly owned pipeline, we believe we have multiple opportunities for both Barbara and our PD one inhibitor Gtx 40 14.
Specific to Gtx 40, 14, we'll be presenting new safety and preliminary efficacy data from the phase one study at Citi Tomorrow November Eightth.
We're also excited to announce that these preliminary data support the use of Gtx 40, 14, as the PD, one inhibitor and the predictive biomarker combination trial with Oprah.
Turning to our translational science platform, we continue to use this high science approach not only for the reverse translational analysis for clinical development, but also to drive our target identification and discovery pipeline.
Our broadening discovery pipeline includes multiple programs targeting T regulatory cells macrophages and stromal cells.
We continue to believe the best approach to identifying novel I O therapies is to build a pipeline of programs targeting diverse immune cell types.
Our next development candidate is on track to advance into I IND, enabling studies by the end of the year.
Moving now to some of our corporate accomplishments, we were pleased to announce key appointments that further strengthened our management team.
In September we announced the appointment of Jackie Fahy, Sandell, as Chief legal officer and corporate Secretary.
She brings a wealth of in house biotechnology and pharmaceutical legal experience and we believe her expertise will be a crucial asset as we continue to progress the company and execute on our mission of transforming the way cancer is treated.
Separately in October we added Dr. Haley Lincoln VP of program and portfolio strategy to the management team.
Haley has been leading our development programs, including the planning and decision making around the portfolio since she joined jobs in early 2018.
As we head into 2020, we are well capitalized to continue advancing both our ongoing clinical programs and discovery pipeline.
We remain keenly focused on interrogating the underlying mechanistic science, however, immunotherapies and identifying the patients likely to respond.
I'll now turn the call over to best to discuss our pipeline in science in more detail. Thanks, Rich and good morning, everyone I'd like to provide more detail on the recent highlights from our pipeline.
We're particularly pleased with the progress we have made to date with Oprah our phase to emerge trial of Oprah in combination with HP in PD, one experienced patients with non small cell lung cancer or bladder cancer is underway.
These patient populations represent a rapidly growing area of unmet need.
As PD, one inhibitors move into earlier lines of therapy with few options and no established standard of care for patients who progressed after a PD one or PDL one inhibitor.
PD one inhibitors have made great strides, but unfortunately, the majority of patients do not respond to therapy.
As the primary activity of PD, one inhibitors impacts CB eight so we believe that focusing on the critical role of CD for cells may help address this unmet need.
The open label Multicenter emerged trial builds upon the fundamental science by our founders as well as the reverse translational analysis from our iconic trial.
This science supports the role of it be in inducing I Cotai CD for T cells prior to vote for administration.
Our founders demonstrated that if the induced I close high Cdfour T cells and that improved clinical outcomes were seen in patients with sustained level. So by Cosac Cdfour T cells. We also demonstrated that I could take CD for T cells are not induced by PD one inhibitors.
In iconic we demonstrated that improved outcomes in patients treated with Oprah alone or in combination with nivo were associated with emergence expansion and sustained activation of Iqos high CD for T cells.
Additional experiments indicated that volpara can exert its activity only on CD for T cells that already have high levels of Vikas.
The emerged trial AFFO per NDP includes a new combination dosing and sequencing strategy based on our understanding of the kinetics of induction of I close I see before T effector cells by it be and built Brett.
As rich mentioned, our city poster on Saturday will provide the scientific rationale for the study and the combination dosing and sequencing strategy, which we believe optimizes, both I Cotai Cdfour T cells and agonist biology. This addresses a critical point in the Io field.
Combinations are typically co administered but in our view it is critical to understand the mechanistic context, and best dosing schedule to optimize the immune response, we're happy to continue to work with our outstanding founders in this regard.
In the initial stage of emerge we expect to enroll up to 80 patients with non small cell lung cancer or bladder cancer. The primary endpoint is overall response rate and secondary endpoints include safety duration of response progression free survival and overall survival.
Additional important assessments will include close monitoring of Iqos high CD for T cell emergence and a range of other biomarkers, we expect to report emerged data, including preliminary efficacy and biomarker relationships to clinical outcomes for up to 80 patients in 2020.
As rich mentioned, we're in the planning stages of additional phase two studies of Oprah, including a trial using a predictive biomarker to identify patients more likely to benefit from the combination of Oprah and to PD. One inhibitor. This would not have been possible without the intensive reverse translational analysis of the.
Konik data and our dedication to finding the right immunotherapies for the right patients.
In iconic we analyze the relationship between several baseline potential predictive biomarkers the vote for associated Ico say Cdfour T cells and clinical outcomes. We looked for differences between those patients who showed emergence of ico size CD for T cells, and clinical benefit and those who didnt.
Got it.
Through this analysis, we have identified a predictive biomarker that we believe may identify patients who are more likely to benefit from a combination of oprah and to PD. One inhibitor. We will provide more details in the next few months, a new clinical studies, including the biomarker approach.
Turning now to Gtx 40, 14, we will be presenting encouraging safety and preliminary efficacy data tomorrow at Citi.
We're very pleased to have sufficient data to support the use of Gtx 40, 14, as the PD one inhibitor in combination with our other product candidates, including with Oprah and the new predictive biomarker trial, the ability to conduct clinical trials for two agents in combination from our wholly owned pipeline.
It is a major step forward for gem.
The progress we have made to date across our entire pipeline is a testament to the strength and promise of our translational science platform and reverse translational analyses. We continue to focus on the underlying mechanistic science of our Immunotherapies as we work towards bringing meaningful and long lasting benefits to us.
Cancer patients.
Now I would like to turn the call over to Kim for a discussion of our third quarter financial results Kim Thanks, Beth good morning, everyone.
As we reported in this mornings press release cash cash equivalents and investments as of September Thirtyth 2019 totaled 185.1 million compared to 195.9 million as of December 31, 2018.
The decrease was primarily due to operating costs incurred during the period offset by the $50 million license fee received in July 2019, pursuant to our new license agreement with Celgene.
Turning to the piano I license and collaboration revenue was 119.4 million for the third quarter of 2019 compared to 14.5 million for the same period in 2018.
Revenue for the third quarter of 2019 was comprised of 50 million of cash received under the Gtx 80, 64 license agreement with Celgene and 69.4 million of noncash revenue.
The noncash revenue represents the remaining recognition of the Celgene upfront payment received in 2016 under our original strategic collaboration which was terminated in the third quarter of 2019.
During the third quarter of 2019, we incurred 15.1 million in research and development expenses compared to 16.8 million for the same period in 2018.
The decrease in expenses was due to lower external R&D costs, partially offset by an increase in employee compensation costs.
General and administrative expenses were 6.5 million for both the third quarter of 2019 and the same period in 2018.
Net income for the third quarter of 2019 was 98.9 million or net income per basic share of $2 to 99 cents and net income per diluted share of $2.90 as compared to a net loss of 7.6 million for the same period in 2018.
Or a net loss per basic and diluted share of 23 sets.
This increase was driven by the 119.4 million of license and collaboration revenue recognized during the third quarter of 29 team.
Based on our operating in development plans for the remainder of 2019, we have narrowed and lowered our guidance on gross cash burn on operating expenses and capital expenditures for the full year 2019 to be approximately 75 million to 85 million.
This is compared to our previous guidance provided in January 2019 of 80 million to 95 million.
With our strong balance sheet, we continue to have the flexibility to drive our innovative immunotherapy pipeline, while efficiently executing against our strategic plans and goal.
Furthermore, we also have full strategic flexibility with respect to developing our immuno oncology programs, including whether and when to engage new partners.
With that flexibility, we will continue to execute on our science based approach to create the most value for patients and shareholders.
With that we would now like to open the call for your questions operator.
Ladies and gentlemen, good question, you would need to press star one under telephone.
Withdraw your question press the pound key.
Please standby, we compiled acumen a roster.
Our first question comes from Cory Kasimov of Jpmorgan. Your line is open.
Hi, Thanks for taking my question.
You talk a little bit about helping us and enrollment is going in the emerge study.
The.
And then also just any context you can provide.
Hi.
Jason.
Any sort of Russian level just fine.
Okay.
Sure Hi, this is best so we're pleased with the enrollment in the emerge trial and we remain on track to have data in 2020.
We haven't given any more specific guidance than that at this point, but we are on track to have data in 2020 from the from the first stage of that trial.
Regarding the ico size Cdfour cells, we internally have very clear definition of what's required for that we're measuring them in a validated assay at an outside vendor.
Don't believe we've shared the definition that we use in the trial.
It's done by flow cytometry, so it's a flow cytometry assay done by an external vendor with a validated assay and we'll continue to fall continuing to follow those cells very closely in the emerge trial.
Okay, Great and then one more question just on Opex.
You mentioned that you're.
Following the burn rate for this year, but.
Any kind of God help provide.
Next year.
And how we should it back.
Increase.
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Sure. This is Ken so yes, we did narrow on guidance. We typically do this as we get closer to year end, just having a better understanding of where we are also with the outlicense of Gtx 80, 64 to Celgene earlier this year as well as a conscious effort to really contain costs that have given where.
For the market is in the current state.
Of the market, we have narrowed our guidance as far as 2020 and going forward, we will give guidance at the start of the year typically we do that at your conference. Once we have a better sense of our budget I still feel comfortable in saying you know with 185 million that we ended the third quarter with Thats still I'm a proxy.
My two years' worth of cash.
Okay, great. Thank you.
Our next question comes from four Speaker of Cowen Your line is open.
Good morning.
Another question on the emerged studies for the items expression level I'm, just curious are using archival of fresh tissues.
And do you have any sense, how that too would correlate.
Yeah, Hi, So this is not the I coasts H.C. that I know you've been with us since the beginning so this is not the I coasts I see on tumor tissue that we started out the study with when we talk about ico size Cdfour T cells. This is actually something we measure.
In the peripheral blood of patients who were on treatment and what we've seen is that these sales begin to appear on treatment with Oprah and increased to a substantial proportion of the peripheral blood CD for sales and remain elevated in the patients.
You are responding and we have people ongoing over two years at this point and we continue to see elevations of these activated CD for T effector cells in the peripheral blood. So I'm glad you asked that question because I don't want people to confuse this with the Ico say H.C. that we started out with this is a per.
Referral blood Pharmacodynamic biomarker, it's done by flow cytometry and it measures.
The percentage of.
I'd for T cells in the peripheral blood that have high levels of like us rich going to add something to that yes, maybe just add to that as well where is the you know we've seen that it's quite prominent tracks with clinical benefit and so weve as we've studied those cells. We have done a fair amount of characterization and we think.
They have all the right features to be truly pharmacodynamic biomarker of Oprah activity not a PD one activity and that includes you know they're not T regulatory cells. They have all the characteristics of effector cells to bet positive all the kind of.
Each one kinds of.
Science associated with these cells.
So there's been a rationale for even kind of stopping treatment for patients that don't have this elevated cdfour cells. Shortly after treatment star.
That's it really interesting question, what we emerge.
Identified in the iconic trial is that.
Can take a while for us to for these sales to reach levels that we can measure in the peripheral blood and so in general we saw emergence of these cells.
In monotherapy around the same time that we saw response. So there's no indication right now that if you don't see them you should not continue therapy I would say it's more the other way if somebody if we see emergence of these cells and the patients may not have responded yet it would be an indication to keep the patient.
On therapy with the expectation that you might have clinical benefit to follow.
Great and my last question is on the combo study that you're doing with PD one.
PD one from a regulatory perspective, I mean, the FDA would see too on approved drugs being combined and single study curious how do you see that would be developed what kind of study design would you have to do what would that have to be kind of permutation studies.
Do you thoughts on that.
Sure. So unfortunately for us the FDA has issued very clear guidance on the novel novel drug pathway and in general at some point prior to registration they require that you show.
Either that either drug alone is not sufficiently active or demonstrate in a clinical trial that the combination is superior to either of the drugs as a single agent. So art, we have a fantastic head of regulatory we have very good understanding of the guidance for that and we have mapped out potential.
Greg registration paths for.
For the combination that we feel our eminently achievable.
Yes, maybe I'll just add just to complete that Petrobras in that part of the study that's where we were able to see from iconic.
And pick up the baseline.
Predictive biomarker so as we go forward with that combination using our own PD one inhibitor, that's where we'll also be selecting patients that we think are more likely to produce these cells.
Gotcha, great. Thank you very much for taking my questions.
Thank you.
Our next question comes from Mike Olson of Baird. Your line is open.
Hey, guys. Thanks for taking the question.
Hey, Mike just wondering how are you.
Thank you spoke to the second development path for Oprah.
Sounds like you're making progress there I don't know if you can comment on on the baseline biomarker, you're using there and maybe how it's different from your.
From that use in the sort of peripheral blood for the.
Emerge study and then maybe just the status and next steps if possible. Thanks.
Sure. So I think yeah the importance of.
The link between the predictive biomarker and the Ico say Cdfour T. Effector cells is that in addition to we were we were looking for potential predictive biomarkers in the iconic study and when you're trying to figure out which one maybe the best you always want to link it to clear.
Nickel outcomes and so you look at the pit at the baseline samples from people, who responded who didnt respond and see if theres anything in the baseline samples that can help you predicts the people who had benefit I think what really strengthens that for US was that we not only link these potential.
Baseline predictive biomarkers to clinical efficacy, we also linked it to the emergence of our drug specific pharmacodynamic biomarkers. So we're really tying all the pieces together and so it was really having that biomarker. In addition to looking at the clinical outcomes that enabled us to identify.
Hi, this predictive biomarker.
We will provide more information more specifics about it over the next few months and look forward to.
Sharing the data that we have with it and talking more about it in the coming months.
Great. Thank you.
Thank you welcome.
As a reminder, if we'd like to ask a question. Please press Star then one.
Our next question comes from Debjit Chattopadhyay of H.C. Wainwright. Your line is open.
Hey, good morning, just wondering a from a clarification perspective, what exactly is being presented at this at sea meeting regarding the most study is it just the sequencing strategy or some early preliminary biomarker data from.
The patients are being enrolled in large.
Thanks for that question dengue. So this is best again. So this is a clinical trials in progress poster. So the we're not allowed to include any data from the trial. The purpose of the truck of the poster is to provide the scientific rationale and design of the study. So as you may recall.
Weve hinted at the fact that we have a new schedule, but we havent provided any details up until now and we felt that now is the time to reveal that dosing and schedule and sequencing strategy that we're employing in the trial as I mentioned, we believe this not only optimizes the ico size see before.
T cell biology, and the kinetics of induction by it be and then the sustained.
Proliferation and activation by low Brett, but we also think it addresses some of the issues of agonist biology that have made them so challenging to develop up until now. So thats included in the poster. So there is some in vitro and preclinical data in the poster, but it's providing the rationale for.
For the dosing.
Schedule and the sequence of it'd be in Bopera in the in the study.
Great and and in terms of what do you have so far observed in the and mud study is there any.
And she can throw about or elaborate upon the percentage of patients who have a robust induction of ficos high sales following the CDN afford induction.
So we will definitely be looking at that and presenting that data when we present the clinical data in 2020, but we're not going to give any hints before then.
And.
So as far as I understand this subject to the Android India. Much study have they're not primary PD wonder if refractory right Theyve had some degree of response by the partial response or stable disease.
Yes.
Sure we don't actually require that they have responded they have to have been on a PD one inhibitor or PD one inhibitor for at least three months and we did that to rule out the people who come off in the first month or two because they're refractory, but we don't require.
Prior PR. They may have had stable disease. They just had to have been on.
For at least three months.
Great. So.
Any details EDA from within Jounce, all three of collaborators regarding the patients had looked last one genotype, especially the heterozygosity because that seems to be very predictive of responses to checkpoints does that also.
Going forward and impact.
Hi cause elevation.
Yes, we have it we have that.
Made that connection in terms of the you know the is the assessments of those patients going into that study.
We as more and more of these.
Associations.
Become become established we certainly want to look at all those but there's nothing that's kind of guiding patients into the study along those lines right. We're collecting baseline samples to be able to assess that and host of other things, but they're not part of the eligibility criteria.
Great and just one last question then and so in terms of the stagger between the ongoing and much study and the predictive biomarker study.
Which obviously is in combination with Gtx for 14, how should we think about it in terms of keeping an eye on the balance sheet or having a better handle on the emerging data from the Cdfour combination. Thank you so much.
So I think I'll start with Adam can may want to add so we expect.
Starting with the emerge there will be data rolling out over the next few quarters. After we start.
That after we first release the emerged data with data from additional studies and as I think you know we are very conscious of being.
Taking good care of our balance sheet, and making sure that we're not spending money.
Without very good reason and with very specific goals in mind, So maybe I'll turn it over to color. So that the this is Tim well give more color as we rollout our specific plans and get our budget finalized for 2020, but when we do our own long range planning and when I give comments about how long I think the cash runway will laugh that end.
Fluids. This full phase two program that we have in front of us for both brought and 40 14 together. So it's the of merge it biomarker and a few other things we'll talk about in the future, but we have all of that built into our planned runway over the next couple of years, yes, including the just in the scrip.
That we spoke to.
The R&D, enabling studies that we have planned for kind of the next the next level candidate that will bring to the clinic.
Great appreciate the color. Thank you.
Okay. Thanks.
Our next question comes from Jim Burke enough of Wells Fargo Securities. Your line is open.
Good morning, it's Nick on for Jim This morning.
Hello.
Good morning, and a couple of questions on on the biomarker identification up so.
And can you provide some background on whether that was a final series of candidate. So was this biomarker.
Fairly obvious from the starts and then in terms of sensitivity and specificity can you give us some idea of the pulp false positive rate false negative rates and and whether you need to develop a companion diagnostic at this point him.
Thanks, Nick and his best So we had.
Pre specified list of potential predictive biomarkers.
From the very beginning of the iconic study that included a range of both you know I see type things genomic analyses and so.
This is one of the things that we had identified.
And we're very pleased to see the correlation as I mentioned with not only clinical outcomes, but also the vote for specific PV biomarker ACO size CD for T cells. So linking all of that together has been very important.
And.
So yes, I mean, it was one of the things we had intended to look at and it and it proved to be something that we think.
May helped to identify patients more likely to benefit in terms of the sensitivity and specificity as I mentioned, we'll be giving more information about this biomarker over the next few months and we look forward to presenting the data from the iconic steady that supports it and hope to do so in the future.
And then we'll be able to answer your questions in more detail rich may want to add something yes, sure I'll add made a comment to that so I think you don't look we have had on our posters you know.
You know kind of the standard panel you'd look at PDL. One staining was this all MSR a high patients that we can kind of rule those those out so those have been on our posters over the past.
Few few meetings.
The key for US just to emphasize it again that I think no. Beth also emphasized is for US we really wanted something that would help capture the volpara specific PD activity in that sense, we believe we're kind of capturing that.
PD activity linked to CD for cell biology, so that was kind of the key elements of the biomarker search and assessment others that we tested you know you may have seen something here or there, but nothing that we felt operationally we could really put into play until we've come out with.
With this this result, which will be disclosing more in the in the coming months.
Thanks, So just just a follow up mean and you know.
Pass I am thinking a little too hard on this but instead a biomarker that.
If you need to screen several hundred patients so to look for de Novo biomarker as you say operationally that's going to be very challenging in the clinic. If it's really looking at something that perhaps is in the patient record that you need.
Or build from.
That operationally makes it much easier to run this study.
Sure, So and I actually Didnt answer the last part of your question. So.
Yes regarding a companion diagnostic.
I think from the very beginning that.
Something that we would hope to do to be able to develop companion diagnostics for our drugs. So that we can match the right immunotherapy to the right patient.
Regarding the biomarker.
Again, I can't get into too much detail right now, but we are definitely cognizant of all the challenges of using a screening test and we have a strategy to address that and.
Members of my team have done this before we have a lot of experience in house with.
Predictive biomarkers with screening patients for.
For drug related Biomarkers. So we believe that we have a good strategy in place to address any challenges.
Okay. Thank you.
And then just sort of moving to emerge. So you spent a lot of time sort of getting this immunologic training and moving into right direction, you say brokers going to sustain.
Is both a sufficient to sustain that goal for moly. The analysis you've done now you have begun to identify.
Additional leverage that you might be able to address to further amplify.
A response, obviously more obvious for might be 40 14, but.
Should we be expecting.
Weve Ms emerge to which looks at okay. Now how do we amplified this response.
BPMI deepen the response sure sure Thats a great question I.
I think the complexity of the immune response to cancer and getting all the different pieces right is certainly one that we think about a lot.
We decided.
For emerged to really focus on.
On the biology between it'd be invoke FRE, because it's the cleanest way to test our hypothesis that being said, it's great that we have our own PD. One inhibitor. So you know at relatively low cost if we decided that a PD one inhibitor could be added.
To the mix, that's something we could do and but at this point, we feel it's important to test the hypothesis as cleanly as possible without muddying it by adding another compound, but it's certainly something we could do.
Good afternoon, just lumpy sorry.
Sorry, the emerge patients of course, our PD, one experienced exactly and so that was part of the rationale the setting to try to keep that is kind of clean as possible.
Okay, and then just last one for me and and I think in your prepared comments rich.
You.
When we're talking about future studies, you use apparel trials.
A biomarker trial. So can you just elaborate on what additional trials timing number that you're thinking of.
Yes, we'll we'll give more and more clarity on that in the next few months.
Fair enough, Okay, I will see you.
At the post.
Okay.
Okay.
Yes.
Our next question comes from Steve sees House with Raymond James Your line is open.
Hi, good morning, the biomarker that you identified.
<expletive> the emergence of vehicles high.
Sales do you think it's specific to volpara or would it work for any ghosts agonist and related lead heavy or could you protected with IP as a companion diagnostic.
Yes, those great question, Steve, but I think until we until we until we reveal that you probably don't want to pick apart those individual.
Pieces of the question.
Okay.
Okay, well, maybe I'll ask about the some of the data in a duck then the.
Corporate DECT phone line, you're showing persistence.
There is a nice chart that shows sort of a relationship between durable a partial responses and persistence of the oncocyte she'd be 14 cells above 5% threshold that looks like that's 5% referred to percentage Cdfour T cells that are articles high just wondering why a 5% is the critical threshold, there and how that was determined.
Yes, so that was determined somewhat empirically, Steve so when we identified the ACO size cells from patients.
Retrospectively from.
My contact we you know we it was clear that was treatment emergent and so as we look at that assay. The kind of empirical data is that the 5% or below we can't really you know distinguish the noise of that but once you start to see the.
T cells emerge in climb in percentage of the CD for compartment and sustained over multiple testing periods. That's when you see those trajectory is go up and so thats really kind of a baseline underneath that is too hard to call. So the.
Vertical evidence is when you're above that those are the patients that benefit there yeah. There other elements to our definition of the ico size cdfour cells.
So thats not the only thing we're using its a very very rigorous definition.
But I think to riches point, it's that's the minimum but I think what's really clear from that graph is that most of these patients at over 50% of their peripheral blood cdfour cells are ico site.
Yeah, and then you also mentioned they're connection with the durable PR is one of the things that we've been very excited to see is that in three out of the four responders their target lesions have actually completely disappeared. So although they are still technically p. ours because of some residual non target lesions.
They've had a very very nice response to the drug and just for people who aren't aware of the difference. So target lesions are the the lesions that are.
Finally, measurable that that the investigators use to satisfy the resist criteria. You know you measure the percent change from baseline in the tumor non target lesions tend to be a small lesions lesions that aren't easily measurable that that could be or a representation of the cancer.
So the fact that the target lesions disappeared in three out of those four responders. We think is very encouraging and that that correlated with the sustained presence of the echo's I see before T cells.
Yes, slightly larger picture on that Steve I think there is.
Considerable wait now behind the idea that with PD, one inhibitors, you unlock the CDH cells in the tumor, but they already have to be there. That's that's what you get is unlocking that population out of that therapy. So then the question becomes with the immune system. How do you provoke that kind of continued.
Continued immune response and so we're we're encouraged to see that the cell stay there. The durability continue the responses the responses deepen.
Okay that too.
Thanks, Thats really helpful. At two quick follow ups just on the kinetics of T cells will that chart specifically one is.
The one gastric cancer patients on 0.1 rig for Kate.
FFO for up plus Opdivo so they.
They reach sort of by like day, 100 about 30% Ico cells, and then measured zero a few days or weeks later and then started to go back up over subsequent measurement. So there are positive clearly and then totally negative and positive again I'm. Just wondering why that might be is that a technical limitation of either Sam.
Bill collection or the assay or is that a real biological result, and so what does a waxing and waning of the cells sort of a earlier time points say about the biology. So that's question one I'm just that one patient on and the second question is.
Sort of broader trend is that.
These cells are increasing really out a year or even a year and a half and sort of peaking.
So it's a it's a really gradual build obviously you get responses pretty early on.
So what is that trends sort of over the full year year and a half of increasingly cells to peak say about the biology.
Thanks, Yes, that's a great. It's a great question, Steve you know, where we had our and our fathers or.
Certainly.
Thinking about that.
Our view is that.
Supported by this data and the kind of the continued pharmacology, we can do and studying the mechanism in the in the lab.
Yes.
You know a view that to get these cells you need AG heico's high cells to start you need walbro onboard and you need antigen in the system. So when you have those three things correctly in the in the patient that's when you see this kind of pronounced.
So you know expansion of these cells into the CD for compartment importantly, the city for compartment does it doesn't expand itself. It just turns over into ico size cells selective T cell receptors are being expanded has all the right characteristics to it.
So we think the kind of the interplay of the biology really.
Starting with the Ico size sells both brought onboard and it seems to be sustainable to be able to do this but of course, you've got to have the antigen and.
Beyond that we will can still continue to kind of.
As a part this mechanism, which we can now due in the lab in.
You know kind of cell culture and animal studies.
Maybe that the second part of the answer to your question is that.
You know the assay well collection of the cells, making sure we have enough viable cells to do the assay can be challenging. So there may be time points that we are missing or that the samples not as good I don't have a great explanation for the fact that onetime point dropped out right other than that if you can see.
Clearly that the patient has had sustained.
Hi levels of the self yes, yes, I think that's too little data to try to link that to a dose if that was part of your question, Steve right and and in that particular patient lease. We didnt have the earliest nearly samples, yes, and we've gone to great lengths to make sure that we have good sample collection in the emerged studies. Since this is something we think is very important to follow.
Great. Thanks rarely if I appreciate it.
You're welcome.
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