Q2 2022 Cue Biopharma Inc Earnings And Business Update Call
[music].
Greetings and welcome to the cue Biopharma update call at this time all participants are in a listen only mode. A question and answer session will follow the presentation. If anyone should require operator assistance. During the conference. Please press star zero on your telephone keypad. As a reminder, this conference is being recorded I would now like to turn this call.
Over to you Mr. Dan Maseri cue Biopharma Chief Executive Officer. Thank you Sir you may begin.
Okay. Thank you and good afternoon, everyone just to remind you as we proceed through the presentation will convey which slide we're on and you can advance the slides directly.
We appreciate your time and interest in our update call regarding our ongoing trials.
Q1 O one as well as Q1 O two.
Initial representative drug candidates of the IL two based cue 100 series joining me on today's call is Dr. <unk> <unk>, our president and Chief Scientific Officer, Dr. Ken Pienta, our acting Chief Medical Officer and Dr.
Dr. <unk> <unk>, our senior Vice President of clinical development, and carrying Malone, our Chief Financial Officer.
Conference is being recorded and will be available on our website for the next 30 days as a reminder, and as shown here on slide number two of this presentation at.
Oh, you may contain some forward looking statements any forward looking statements made during the call represents the company's views only as of today August 23 2022.
So.
Our agenda for today's call is shown on the next slide.
As an introduction and each will provide a synopsis of our progress to date as well as describing our strategic and competitive positioning prior to turning the call over to Ken <unk>, who will provide a summary and status update of the data associated with observations from our ongoing phase one trials of Q.
101, as well as the recently initiated Q1 O two trial.
Following cannon Mateo I'll provide an overview of our corporate strategy and additional pipeline.
Expansions within the cue 100 series.
Cary will then provide a brief update of our financials after which I'll return for closing remarks, and then open up the call for a Q&A session with that I'll now pass the call over to a niche.
Thanks, Dan I'd like to start today's presentation by reminding folks of the Genesis of our company's quest and.
The mission, we seek to accomplish.
Mission is to address it very fundamental and clubs sequential question sort of immunotherapy, which is can we selectively and specifically activate anti tumor T cells, while avoiding the carpet bombing of the immune system to maximize efficacy and minimize toxicities. This is a very basic fundamentals.
Stinker from how others may be approaching the challenge of turning the immune system against Kansas to.
To accomplish our objective as shown in slide four we envisioned exploit into one unique market often anti tumor T cell, which is the tumor specific T cell receptor or TCR.
We've engineered and innovative biologics platform termed immuno stat that generates TCR selective engages to deliver immune activating signals to tumor specific T cells.
Figure on the left in slide four depicts the cost structure of an immuno stat, which is essentially an antibody FC based biologic containing stabilized tumor peptide HLA molecules to selectively target tumor specific T cells, along with desirable activation signals that are consumed by those T cells. This framework.
The molecular basis for improved specificity for anti tumor T cell activation, while minimizing off target toxicities due to systemic immune activation, which by the way. It continues to be a key impediment for many other broadly targeted immuno therapeutic approaches.
On the right side of this slide you can see the figures depicting the cue 100 series, which is designed to selectively deliver IL two to tumor specific T cells.
Irrelevant T cells, hence generating the therapeutic index or IL, two which as of yet has been a challenge. We believe this is a superior approach, but honestly the fullest potential.
Well too, especially since the tumor specific T cells are present in a very low frequency current political candidates, namely Q1 to one in Q1 O. Two derived from the cue 100 series and shared our core IL two framework as depicted here. The next slide slide five summarizes the key and.
Impactful takeaways that highlight the progress and clinical validation of our approach Kennan Matteo will provide detailed insights into the clinical data and patient benefit that support the conclusions noted here to summarize we've engineered in novel Biologics platform immuno stat for selective targeting of event that you would think selecta.
Nation as an initial drug construct we chose to deploy <unk> towards the targeted activation signal.
IL two is a well characterized and validated therapeutic target, but as suffered from significant safety liabilities due to lack of a therapeutic index.
We have successfully generated a therapeutic index, where IL two as evidenced by the fact that we have observed political activity between one big Mckagan full makes the keg and have dosed up to eight mixed vacate with no M. T. D. Most other Ohio two variants that have indicated they have been dosed in the low microgram per kilo.
Gram range due to unwanted adverse side effects.
First clinical candidate in Q1 O one targets IL two to HBV specific T cells to attack HPV, driven cancers, such as head and neck cancer clinical experience with cue 101 highlight several important findings for our technology platform, our molecules are well tolerated with no evidence of <unk>.
That make IL, two toxicities, such as vascular leak syndrome cytokine storms, they exhibit drug like properties, including favorable PK on target PD signals and monoclonal antibody like manufacture ability to support desirable cost of goods, we have demonstrated clinical efficacy as monotherapy in late stage cancer.
Patients that are favorably numerous prior therapies, including checkpoint inhibitors Kennan Matteo will describe these signals in detail, including an emerging benefit in overall survival.
The observed clinical benefit is supported by mechanistic signals, demonstrating T cell infiltration, which capitalized our ongoing neo adjuvant trial in head and neck cancer, we have evidenced prolonged benefit and anti tumor activity in patients remaining on therapy for long periods.
Which underscores the extended Cognetics for evolution of a beneficial immunotherapy response as also noted previously by others.
Lastly, early data from our first clinical experience in combo with the checkpoint inhibitor. So both the potential for significant expansion of patient benefit all of these metrics will be described in greater detail in the ensuing political discussion.
Fortunately since the core IL two framework is conserved across the cue 100 series, we believe the clinical Derisking obtained about Q1 O. One has essentially de risked our entire platform. The recent IND acceptance for our next clinical candidate Q1 O two targeting wilms tumor one well WT one undisclosed.
The strategic advantages of platform Derisking accomplished by Q1 O. One the FDA accepted the Q1 or two I N D with no requirement for preclinical talks and has authorized us to initiate the trial at one milligram per kilogram dose that that has demonstrated clinical activity in the cue 101 trial and as I say.
Secondly, highest starting dose than the 0.06 megabit kick starting dose for Q1 O. One these metrics highlight the resource time and operational efficiencies gained by the platform Derisking by Q1 or what.
So and we believe the modularity of our platform coupled with a clinical validation positions us to generate a rich repository of therapeutic molecules targeting many kansas as one evaluates the potential of volume throughput cancer immunotherapy. We believe our platform has cracked the code, but selective targeting of the cytokines to the tumor specific.
T cell repertoire that will address this in context of our corporate road strategy towards the end of two days today's presentation with that backdrop I'll now pass the call to Ken for the clinical update Ken.
Thanks, Denise and good afternoon to all listening to this call. We're excited to be presenting our updated data from the ongoing Q1 O. One phase one trial as both a single agent monotherapy in third line and beyond head and neck cancer as well as the encouraging emerging early data from the combination study.
With pepper loser Mab in first line patients.
Previously and consistently stated we believe Q1 hundred one's mechanism a mechanism of action as evidenced by the ongoing data generated to date to date provides effective and tolerated dose levels, enabling selective stimulation of tumor specific T cells.
Current head and neck cancer testing terrible disease. The data we have observed throughout the monotherapy trial enhances our confidence that Q1 on one and stimulating cancer specific T cells in a subset of these patients with a resulting anti tumor effect.
Furthermore, and more importantly, we continued to observe an evolving trend of enhanced survival.
And while this data is still maturing we are encouraged by the observations to date clinics.
Clinical observations beyond the overall response rate and median overall survival continue to bolster our confidence in the anti tumor effects in Q1 O. One.
For example, we have observed patients experiencing tumor reduction after a prolonged period of time drug where no reserve base.
Based objective response was initially observed by imaging.
Observation consistent with observations made by other <unk>.
Demonstrating the kinetics of T cell anti tumor activity that manifest over a long longer period of time.
This pattern can be seen in the tumor measurements plotted out on slide six for a patient receiving Q1 on one and two megs per kg, where we can see that the first several months appeared to demonstrate tumor grow even beyond the 20% threshold used by resist criteria.
However, we do.
Based on the overall clinical status the patient with continued on treatment after we.
Change the protocol to allow this so.
So after approximately six months the tumor began to shrink and the patient remains on therapy 14 months after starting treatment with cue 101.
The data presented on slide seven from a patient treated at the RP to D. A forming per gig demonstrated stable disease lasting close to 12 months and ongoing.
With sustained reductions in cell free HBV DNA, a biomarker that may reflect disease activity in patients with HPV positive cancers and in fact this is a test that is increasingly being used by experts to guide treatment in these patients.
This may represent a pattern suggestive of a pathologic CR.
Taken together these data build our confidence in the therapeutic potential of Q1 O. One and then the potential path forward for registration study as a monotherapy in patients that have failed prior chemo therapy as well with checkpoint inhibitor therapy.
We plan to present additional data at an upcoming medical meeting I'll now turn this over to Matteo to talk more about this in our other data Matteo.
Thanks, Ken the goal in our Q1 O. One monotherapy study was to first prove safety because it's first in man biologic and second to prove that we could demonstrate antitumor activity.
In addition to the data just described by Ken we have observed in our 20 treated patients at the recommended phase two dose in a monotherapy trial, one PR and seven patients with durable stable disease for an overall clinical benefit rate of.
Approximately 42% the next slide slide eight shows the patient with a PR and Theyre supporting Pharmacodynamic metrics. This heavily pretreated patient has completed 17 cycles of Q1 O. One.
Can see in the two upper right panels that the patient demonstrated a nine fold increase in cancer specific T cells, but did not demonstrate an increase in the general CDA positive T cell population, which might cause unwanted side effects, including immune related adverse events. The patient also demonstrated the transient and modest increase.
In T regs that returned to baseline by day 15.
Patient demonstrated a sustained increase in NK cells, a positive attribute for an anti tumor response as the NK cells may assist in tumor killing we.
We observed similar pharmacodynamic effects across many patients.
On the lower right portion of the slide is a graph showing a rapid decrease in circulating cell free HBV DNA corresponding with the decrease in tumor burden observed by imaging.
We have made the same observation with several other patients who have demonstrated antitumor activity and continue to monitor sell three HBV DNA as a possible predictive biomarker.
Next slide slide nine conveys our ongoing survival swimmer plot for the 20 patients dosed at the recommended phase two dose of four milligrams per kilogram we.
We have taken the liberty to draw a median overall survival lined at eight months, which is reflective of the median overall survival observed in both the keynote.
40 in Checkmate 143 trials of <unk> and Evo the map in second line patients.
As any experienced oncologist understands the survival with third line treatment is expected to be less as the disease is further developed and become more unstable.
Our evolving data continues to support the premise that treatment with cue 101 is clearly trending to increase survival and the third line setting for patients with head and neck cancer.
This data has encouraged our principal investigators and they are aligned with our position that this potentially provides us with a promising path forward to a registrational trial.
The demonstration of monotherapy activity bolsters, our belief that we should see complementary mechanistic effects in combination with <unk>.
As a reminder, the data from patients treated in monotherapy clearly supports that Q1 O. One increases the number of antigen specific T cells.
It is likely that these T cells will have greater freedom to kill with inhibition of the PD one pathway a major mechanism used by cancer cells to prevent immune mediated killing.
Slide 10 demonstrates the Spider plot as shown at Astro. This past June our first line patients treated in the dose escalation cohorts of the ongoing study.
Early data and signs of activity of Q1 O. One in combination with pepper lithium at are encouraging.
With one patient each in cohorts, two and three experiencing a confirmed PR and an additional two patients experiencing durable stable disease. We are continuing to expand patient enrollment at the recommended combination phase two dose and look forward to presenting additional data at an upcoming meeting.
Slide 11 shows the patient from cohort two demonstrating a decrease in all four of their target lesions, including two liver lesions I want to emphasize that this is not just shrinkage in lymph nodes, but shrinkage of visceral tumor disease.
In college as this is a significant and meaningful response. This patient has also demonstrated a clearing of the circulating cell free HBV DNA, which is ongoing as mentioned before circulating tumor DNA continues to be developed and used by our principal investigators as a potential surrogate for response.
As shown in slide 12, the patient with a confirmed partial response from cohort three also demonstrated reductions in all four target lesions, including two parenchyma lung lesions and clearing of their circulating cell free HBV DNA.
We are excited by the preliminary data in this ongoing combination study along with maturing data from our monotherapy or new adjuvant studies and look forward to presenting additional data at upcoming meetings.
I'm also happy to report that we have treated our first patient with Q1 O two which targets wilms tumor one positive tumors in a trial that is enrolling patients with advanced colorectal gastric pancreatic and ovarian cancers as shown on slide 13, Q1 O. Two in Q1 O one sure.
99% amino acid sequence identity.
This enabled us to significantly decrease the development time and cost of Q1 O. Two as we are not required by FDA to repeat our IND, enabling toxicology studies for Q1 O. Two and we were also able to initiate the phase one dose escalation study at one milligram per kilogram the dose at which we observed clear signs of <unk>.
Logic activity with Q1 O one.
As slide 14 shows and as mentioned just a moment ago.
We are performing the Q1 or two dose escalation study in colon gastric pancreatic and ovarian cancer patients. This design offers us the ability to do monotherapy expansion studies in all.
Any or all of the indications being evaluated in the dose escalation phase of the trial.
This trial is actively accruing and will be open at 15 sites around the U S.
I will now turn the call over to Dan to talk more about our pipeline Dan.
Yes, Thanks Matteo.
Described by a niche can and Matteo.
Made significant progress towards the establishment of cue 101, and by implication the entire cue 100 series as a breakthrough therapy for stimulating a patient's immune system against cancer and to remind you that stimulating the immune system directly in the patient's body.
As we continue to progress forward with Q1 O. One in Q1 O two as our lead programs. We also have the potential to rapidly expand our pipeline and productivity.
As conveyed in the schematics shown on slide 15.
However, under the current market conditions, where capital is constrained and resource prioritization is paramount.
We've streamlined our operational footprint and taking prudent measures to foster a focused and strategic prioritization of clinical development and those activities associated with pipeline development fostering strategic partnerships.
Our core approach is to validate and Derisk. The IL two based cue 100 series through the emerging data and associated metrics from our ongoing one O. One and now one O two clinical trials and position ourselves with greater leverage for our retained value creation for our shareholders.
We have promising preclinical data from our K Ras program, which is an extremely important target covering a broad set of cancers with expanded allele coverage into HLA L. Three and a 11 and have preserved as clinically important program for potential strategic partnering.
To be catalyzed by our emerging data from our one O one trial and our one O two trial as well as a possible registration submission in one on one.
We have also positioned ourselves for enhanced productivity inefficiencies with the development of our cue 100 series derivative Richard referred to as Neo Stat, and tailing stabilize molecule as the MHC HLA binding pocket, where the epitope fits in.
That's been stabilized for covalent chemical attachment of an identified cancer epitope.
This will allow for the manufacturing of each allele framework for example, HLA E O to O three a 11, etc.
With an empty binding pocket.
Whereby the epitope, maybe subsequently attached chemically rather than made as a single fusion protein.
This will provide us with cost savings and production efficiencies.
And greater flexibility for epitopes selection in combination such as in the case with tumor instability and heterogeneity.
Furthermore, we envisage that nios that may be an enabling innovation to realize the potential of personalized cancer immunotherapy, where one could sequence the tumor and identify particular epitopes.
Chemically attach those to a neo stat. So while we are currently prioritizing and strategically focusing internal efforts on the development of our cue 100 series drug candidate for treating cancer. We're also actively engaged in strategic discussions with third parties to further develop Q programs outside.
Oncology, including the Q4 hundred series for treating autoimmune disease. These activities aimed at ensuring optimal use of our internal resources on our most advanced programs, while augmenting and enhancing our capacities with third party relationships to further develop promising assets beyond our core focus.
I'm now going to turn the call over to Kerri, who will provide a brief overview of our current financials and I will then return to briefly provide some closing summary remarks prior to opening the call up to questions.
Turning now to slide 16, I'd like to provide a brief update on our financial results for the three months ended June 32022.
We reported collaboration revenue of approximately $26000 and $2 $7 million for the three months ended June 32022, and 2021, respectively.
Search and development expenses were $9 6 million and $8 8 million for the three months ended June 32022, and 2021 respectively.
Increase was primarily due to an increase in laboratory and drug substance manufacturing costs as well as clinical expenses related to our Q1 I've seen phase one dose escalation clinical trial that was initiated during the second quarter of 2022.
General and administrative expenses were $3 8 million and $4 3 million for the three months ended June 32022, and 2021, respectively. The decrease is due primarily to a decrease in stock based compensation and professional and consulting fees incurred during the second quarter of 2022 as compared to the same period in 2021.
We ended the quarter with approximately $66 1 million in cash and cash equivalents and working capital of approximately 67 million importantly, we took proactive steps to decrease the company's office and lab footprint and lease structures expansions, which will afford us significant cost savings that can be allocated to our clinical programs.
We believe our cash and cash equivalents as of June .
June 30 in 2022 will allow us to support the development of our immuno stat platform, including into clinical development in Q1 O. One and he went on to through the third quarter F. 'twenty 'twenty train.
I'll turn the call back off again for closing remarks.
Yeah. Thanks, Gary.
And as you've heard on this call we continue to execute and make significant progress towards further advancing our lead and representative candidate cue 101 towards a potential path for registration.
Through the clinical development of 101 was clearly demonstrated the ability to selectively target and activate defined anti tumor T cells.
While not compromising patient safety.
As seen on slide 17, we have successfully.
Executed and continue to execute well.
On defined strategies, providing risk reduction and validation of the cue 100 series and its derivatives.
As such Q1 O one which is targeting the HLA eight O. Two allele has clearly demonstrated tolerability and single agent activity and remind you with no maximum tolerated dose emerging from the dose range of 0.06 Migs per key.
All the way up to eight mix per kg.
We've seen clear evidence of Pharmacodynamic effect on targeted tumor specific immune cells and T cells as well as natural killer cells. Obviously, the properties that we want to see in the immune compartment.
Clinical activity demonstrated from.
One Meg per kg to form expert kick.
With four makes per kg being a recommended phase II dose and clear evidence of anti tumor activity, which we've gone through some of these data showing a prolonged effect having to do with the kinetics of stimulating the immune system immune system, then dynamically interfacing with cancer.
Clear evidence of the anti tumor activity manifested as a confirmed PR seven durable long standing stable disease with one potential pathologic complete responder that Ken reviewed.
Also we appear to be providing a survival benefit this obviously needs to be determined as to what the median overall survival is but it is clearly trending in a positive direction and we believe it will provide us with a potential path forward for registration.
101 in combination with <unk> is showing encouraging early signs of activity, which we look forward to presenting further details at the upcoming medical.
Meetings later this year.
You went out to the end he was accepted at Onemain kick starting dose and we consider this to be a major achievement basically underscoring the quality of the supportive.
Data, but also kind of underscoring the risk reduction and validation that we believe we've achieved with the data emerging from the 101 trial.
We have evidence of.
Any evidence I should say that emerges in the one or two trial of clinical activity will be a further catalyst for validation and value creation regarding the platforms analog nature and modularity.
And just to remind you wilms tumor one is expressed in a significant range of tumors, representing a very significant market potential in multiple tumor types. So we believe those two programs add significant validation and value for our shareholders and then coupled with neo stat, representing kind of a derivative.
Of the 100 series is a next generation construct providing scale and flexibility one that allows us to address tumor heterogeneity, but also just as importantly, it should substantially decreased our cost of goods and provide us with flexibility that we may even be able to go into personalized medicine and again remind you the attachment of the peptide.
As in the HLA pocket, that's a co bandwidth attachment we have attractive preclinical proof of concept data supporting that premise and look forward to providing you with updates as we continue to progress well.
We're positioned very well strategically and anticipate several important milestones throughout the coming year, including the potential of a registration path for Q1 O. One as a monotherapy are these milestones as conveyed the next slide include Q1 O. One monotherapy with a median overall survival data.
End of year clarifying and this is the potential start of Registrational trial in the second half of 'twenty three.
Q1 O one plus member Luiza map combination that preliminary overall response rate data.
Reading out in the second quarter of next year 'twenty three.
And the 102 monotherapy data, which we've just recently initiated data from the dose escalation will be reading out mid 'twenty, three and to remind you that as a major a significant market opportunity. So any evidence of clinical activity will represent a significant.
Prospective value increment.
Also and importantly, as we focus our efforts and resources on the clinical development of <unk> hundred one in 102, we believe that further clinical datasets will catalyze significant business development and corporate development opportunities for pipeline expansion.
We look forward to providing further details on these trials at an upcoming medical conference later this year.
We'd like to thank our employees and clinical principal investigators, whose dedication to our mission to their commitment and professionalism allows us to continue progressing our goal of helping patients in need and we'd like to thank our board of directors for their support and guidance want to thank our shareholders, who provide us with essential resources to continue.
This important work developing promising immunotherapies for patients.
And most importantly, we want to thank the patients who are participating in our trial and their families.
So their courage and willingness to be part of clinical study, allowing us the opportunity to assess and determine the potential therapeutic benefit of our promising drug candidates.
Thank you very much for your attention and interest I'd now like to turn the call back over to the operator for questions.
At this time well be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate your line is in the question queue. You May Press Star two term, we'll get a question from the queue, but participants using speaker equipment and maybe necessary for you to pick up their hands.
Before pressing the star keys.
One moment, while we poll for questions.
Our first question comes from the line of Stephen Willey with Stifel. You May proceed with your question.
Yeah. Good afternoon, thanks for taking the question and thanks.
Thanks for the update here.
With respect to the updated Q1 O. One data do you have a median duration of treatment at this point I think it looks to be about two months just in terms of eyeballing. It but just wanted to know if that's if that's correct.
And then also can.
Can you just broadly speak to post study therapy that these patients may or may not be receiving following discontinuation of Q1 O. One in I guess your confidence at post study therapy is not impacting just extended out last time that you are seeing off treatment and then I just have a quick follow up on QR too.
Okay. Thanks, Steve can you wanted to say take this questions Yeah, Hi, Steve.
So the median.
The therapy is.
Two cycles, meaning half the patients got to cycles and came off.
I would just point out that that's.
Basically the same as as second line, we see with second line checkpoint inhibitors. So.
It really comes down to what do those patients do.
As far as overall survival because the progression free survival just doesn't correlate as you know.
And as far as follow ups therapies, we're still collecting that data and really don't.
Have that to report yet we.
We do know of some patients that haven't that are doing quite well off all therapies. So we just don't know that data yet sorry.
Okay.
And then just on Q1 O two I know the dose escalation portion and presumably expansion.
Requiring W. T want antigen positivity.
Is this just is this just kind of like a binary yes or no type of assay. That's I'm guessing IHG based or is there some kind of graded expression that each staff in order to be eligible.
Yeah.
It is E.
C based and.
It is graded but are sort of minimal requirement is that 1% of the tumor cells are expressing WT one.
Okay.
Back in the queue. Thank you.
Our next question comes from the line of Ren Benjamin with JMP Securities. You May proceed with your question.
Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress.
Maybe just starting off can we talk a little bit more about the biomarker data that you've generated.
See the circulating.
We're starting to HBV DNA.
Going down considerably better.
And then you know, but but b the tumor.
Shrinkage is occurring but not clearly as much and I and I think you may have called out a pathological CR.
Not too sure if I understand how well that's that's core.
Core being correlated and so can you talk to us a little bit about about that would you use that going forward.
And what other sorts of biomarker activities are you are you planning for these for these studies both with one on one on one or two.
Hey, Ken do you want to take the first part of that and then have Matteo cover the second one.
Yeah, and so on.
Essentially what we're we're seeing what we're what we're seeing is that we have several patients.
With durable stable disease, and as you know with the immunotherapy types of therapies.
Oh type therapies, you, often see sort of a stabilization of disease that could be scar it could be fibrotic tissue can be inflammatory tissue.
And we have the early on we had the patient at Onemain for King who had stable disease.
We ended up going to the operating room and in seeing a you.
You know that that patient and never.
Remainder off therapy for now 14 months or 19 months and.
And then the data that we've been getting from the these ongoing cell free DNA assays, which didn't really exist. When we started the trial.
Was that several of our P is they've started to follow virtually all of the patients.
With cell free DNA to try and get some insight into their disease.
Especially when we you know we don't know when somebody hasn't.
It has an increase in their tumor if that.
By resist if that's more I resisted that and inflammatory change that we should be following what's their cell free DNA is that going up or going down, suggesting it might be more inflammatory or with the stable disease patients.
Do they have any active tumor left and so the data we are you know.
Talked about with this one patient has very stable disease.
Hum.
And that the tumor is is either just sitting there or the what we think is not viable tumors just sitting there a like a scar and their cell free DNA is is zero doubt so that suggests to us.
Based on the other patients that that may be a pathologic CR, if we took that out.
And that is you know.
This whole area is evolving, especially in head and neck cancer and.
And our investigators are learning how to use cell free DNA, it's not accepted biomarker of response by the F. D. A by any means but that's why we're we're trying to.
Really figure this out and learn this and we.
We are you know we don't have all the cell free DNA back yet the data because as you know we do it in batches.
We're very encouraged by it as a biomarker as are all of our docs and we're going to continue to follow that and use that as a potential we are talking about with one of our investigators and tracked about doing in the adjuvant study.
Based on our cell free DNA responses in patients.
I'll stop there and let Matteo talk about what we're doing with WT one.
Thanks, Ken.
I I believe that the questions have been.
Ah well addressed at the point I did want to add one comment regarding the previous question on the WT one assay.
Though we do use a binary result for eligibility.
I just would add that we are paying very close attention and tracking both the nuclear inside a plasmic expression of the WT one by grade so that we can correlate this data with potential patient outcomes.
And sorry, just kind of sticking with this theme for a second are you seeing.
The converse occur in that you know once patients are.
You know kind of progressing our off the study are you seeing H P V. DNA some ph D V D N a pick up in those patients as well or do they consistently stay low all the way through.
So.
Good question what.
We don't have a cell free DNA on the patients after.
They come off study, we just are following them for survival and you know whatever therapies, they've been on et cetera.
But what we what we can see is in patients who are.
Do progress their cell free DNA actually will go up also with it.
Roughly correlates with with tumor burden.
So are we.
We over it's dynamic, but that's why we're still learning about it as a biomarker but.
We don't see it in people who are truly progressing their cell free DNA does go up.
Yeah, I'd add as well Ken that you know this is a an endpoint and in the biomarker assessment that is gaining traction with FDA over the last.
12 to 18 months.
Whereas it may be possible in the future to use it as a secondary endpoint and actually use it to inform decisions and adaptive trial design.
But it's really not there yet so that would be an opportunity in the future.
To introduce.
That biomarker to sort of accelerate or perhaps enhance decision making in the next trial.
Got it.
Second question is when I look at the overall survival curves that you have there.
There are clearly those patients with durable SD. Some obviously with partial responses and then there are those that that clearly have progressed I mean, they're surviving right, but there.
I'm assuming that these that don't have a durable SD marker next to them their their tumors are growing.
And I guess the.
A question I have is have you guys being able to investigate what's what's sort of mechanisms of resistance.
That might be occurring and and as you think about that.
What sorts of combination therapies do you are.
Are you thinking about that could maximize 100 ones durability going forward.
Well [laughter].
The 1 billion dollar question. It's a great question, we honestly don't know of the myriad of resistance mechanisms, which ones are at play what I think is caught.
Caught us certainly surprised early on in court all of our.
Docs are.
By surprise early on is these are these are durable.
Overall survival in these patients that are even have come off therapy fairly fairly soon.
I think you know obviously when we're increasing the number of cancer specific T cells in the periphery and in the tumor itself.
Allowing for checkpoint therapies two to work better.
Certainly we've seen some.
Early indications are.
Potential imaging spread and which would suggest.
That combinations with further side, though.
Toxic types of therapies that are going to increase our neo antigen.
You know amgen too to be seen by T cells.
It is certainly something that we'll consider in the future.
And as far as other mechanisms.
Like HLA downregulation et cetera.
We just don't know yet we don't have that data, maybe a niche wants to comment.
On this but.
Clearly, we think theres going to be synergies.
The obvious ones with checkpoints as well as with with chemo.
Yeah. The only thing I'd add is it's a really important question Glenn we have to look at these analysis.
That has been Oh.
All the way from operational resistance pathway, just because of the TMA to cell types.
Even the tumor intrinsically changing its immunogenicity profile, whether it is because of loss of HLA with lots of.
So the components of outage and processing.
Just need to sort of get a better grasp and listen that that as a part of you know the ongoing analysis of suddenly.
<unk>.
You know enough sort of line of sight, we just need to gather the data.
That will then dictate what possible combinations can we bring in the.
Along with Q1 and wanted to flip to sort of extract even more benefit than what people are already starting to see.
Got it and just one final one for me I probably missed this in the prepared remarks I remember you know we were talking about a new adjuvant study for quite some time and primarily we would've gotten me most excited about it was the ability to have biopsy.
Biopsy samples kind of before and after and like just wanted to get an update as to what was happening with that study.
So.
Okay I'll make a few comments and then I'll probably start it'll tell you do add on so that study is going quite well at Washington, When we've actually already recruited our first couple of patients with other biopsies in place we've got plans in place to get a complete.
Composite batch analysis going soon as a few more patients are the crude that's in locally advanced head and neck cancer Matteo Please feel free to add more to it from your your lines.
Uh huh. Thanks in Asia, that's really quite accurate, we we we've treated.
A bit more than a few and we look forward to the sharing of the data in the future when it when it becomes available.
Alright, thanks, guys.
Okay. Thank you Mitra.
As a reminder, if you would like to ask a question. Please press star one on your telephone keypad, one moment, while we pull for questions.
Our next question comes from the line of Mark <unk> with Oppenheimer. You May proceed with your question.
Hey, guys. Good afternoon, and thanks for taking our questions just a couple for me.
First.
With respect to upcoming interactions with the FDA. It's the plan right now to have the end of phase one meeting in conjunction.
With the availability of MLS data from your phase one trial.
And when can we kind of expect to hear their perspective on our regulatory path forward.
I guess I'm also just wondering why that there looks to be kind of a gap between the availability of MLS data and the potential startup a registrational study. So that's one question for me and the other one is just with respect to the Q1 O two trial.
It doesn't this protocol include.
Our parents.
Biopsy collections.
No that wasn't something that was included in the head and neck study I'm just wondering if any any changes have been introduced so we so we have more translational data.
From the Q1 or two patients.
Tom you want to take that so yeah sure I can start with the question regarding the the interaction with the regulatory agencies. So so as we've just covered here we anticipate having.
<unk>.
Mature median overall survival data by the end of the year.
In the 20 patients dosed at the recommended phase two dose.
And we have designed a phase III trial that we plan to present to FDA in the context.
Of a subsequent registrational.
Trial.
And again, we're beginning to do preparations.
For such an Ah Ah trial at risk and anticipate that we could begin to open that trial, which would be a global multi regional trial sometime later next year.
Okay.
So we do a biopsy as well.
And it'll be one trial.
Yes. So we have you know you're absolutely correct. So we have made in the protocol paired biopsies optional.
We've had a lot of productive conversations back and forth with investigators and we recruited some that are keenly interested and capable of arranging those.
So we hope that in the tumor indications that we're enrolling in the 102 trial, we will have the opportunity to get paired biopsies perhaps.
In anatomic locations in these indications that may be.
If you will more facile and amenable to two biopsy, but to your question. It is an optional.
Procedure at this point.
Whereas in the Neo adjuvant trial by design, we have an opportunity to examine pre and post biopsies.
As a component of the patients intervention all standard of care in the setting of <unk>.
Locally advanced cancer, that's undergoing a resection with curative intent.
Okay, and just going back to the regulatory question.
I just want to be absolutely clear, we wouldn't here until 2023.
Regulatory feedback with respect to what a registrational trial might look like in head and neck cancer is that correct.
I think that that's correct and I would say early 2023.
Of course some of the.
The interactions will really depend upon.
The timelines granted by FDA, but in the setting where companies requesting a type b meeting request, but given where we are in the development that FCA would agree.
Agree and be collaborative and so as not to.
And I the potential of the development for this drug in this unmet medical needs in third line patients and beyond with head and neck cancer.
Okay. Thank you Sir.
Yeah, and this is Ken we certainly.
The end of 'twenty three as you know our conservative estimate we are we know what that trial, we want that trial to be and you know as soon as we get the data.
We'll be ready to go in and hopefully be able to launch sooner at this point.
Got it.
Ladies and gentlemen, we have reached the end of today's question answer session I would like to turn this call back over to Mr. Daniel <unk> for closing remarks.
Okay. Thank you very much.
I want to thank the research analysts for questions are very helpful and instructive.
I just want to thank everyone for listening in and your ongoing interest and support of our activities and bringing these very promising therapies to patients. So thank you very much take care of and we look forward to providing updates.
Throughout the year take care.
This concludes today's conference you may disconnect. Your lines at this time. Thank you for your participation enjoy the rest of your day.
Yeah.
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