Q1 2021 Cue Biopharma Inc Earnings Call
Thank you for standing by this is the conference operator, welcome to the cue Biopharma first quarter 2021 earnings call.
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I would now like to turn the conference over to Dr. George The Boyko, Vice President IR and corporate development.
Please go ahead.
Thank you Shannon and good afternoon, everyone. Thank you. Thank you for joining us on today's call are Dan for theory cue Biopharma CEO Dr.
Dr Niche Suri, President and Chief Scientific Officer, Dr. Ken Pienta acting Chief Medical Officer, Dr material of a study senior Vice President of clinical development, and Carrie Ann Miller, Chief Financial Officer.
Next slide please.
Before we begin I would like to remind you that various remarks of the company makes during this call about the company's future expectations plans and prospects constitute forward looking statements for purposes of the private Securities Litigation Reform Act of 1095.
Actual results may differ materially from those indicated by these forward looking statements as relative there as a result of various important factors, including those discussed of the risk factors section of the company's annual report on form 10-K filed with the SEC on March 9th 2021 as well as the other filings made by the company from the SEC from time to time, which can be accessed.
Accessed on the Edgar database at Www Dot FCC Dot Gov.
In addition, any forward looking statements represent the company's views only as of today may 17th for 2021 and should not be relied upon as representing of the company's views as of any subsequent date well of the company may elect the update these forward looking statements at some future point the company specifically disclaims any obligation to do so even if the company.
Views change please be advised of today's call is being recorded live and archived versions of the event can be accessed via the company's website for the next 30 days I would now like to turn the call over to Dan for theory cue Biopharma CEO Dan.
Yeah. Thanks, George Good afternoon, everyone and thank you for joining us today for a review of our ongoing progress as well as our first quarter of 2020 one financial results.
Which are available in more detail in our form 10-Q filed with the SEC on May 10.
Our agenda for today's call is shown on the next slide slide three.
I'll first provide a brief overview of ongoing progress since our last call highlighting recent developments across our programs with an emphasis upon our lead clinical program Q1 O. One.
After the introductory update I'll turn the call over to Dr. Whitney Sherry Duff, President and Chief Scientific Officer, who will provide a summary of progress and additional platform developments and both of the oncology as well as our autoimmune disease programs. After of niche provides an overview.
Doctor, Ken Pienta, our acting Chief Medical Officer, and Dr. Matteo Love of Sadie, Our senior Vice President of clinical development.
All of each provide a clinical update and review of associated data on our ongoing Q1 O. One phase one monotherapy dose escalation trial.
Matteo will then turn the call over to carry more of our Chief Financial Officer, who.
We will provide a summary of our financial results for the last quarter, and then I'll come back on and provide a brief closing summary prior to opening the call for questions.
So to begin I'd like to remind you of our foundational mission, which is the stated on slide number for <unk>.
Which is to design develop and bring to patients in need rationally engineered biologics that restore immune balance by harnessing natures own queues, hence our name.
For selective and specific module modulation of disease relevant T cells directly in the patient's body.
Through this approach as shown here on slide number five we aim to restore balance of the patient's immune system by activating targeted T cells in the case of oncology and infectious disease or dampening or Inactivating T cells associated with autoimmune disease again of niche will provide further.
Contacts and updates on these approaches of momentarily.
I'd like the first begin with Q1 O one which is our lead drug candidate.
It's currently in a phase one monotherapy clinical trial.
For second line and beyond.
HPV positive recurrent or metastatic head and neck squamous cell carcinoma.
And is representative of our immuno stat platform engineered for targeting Inactivating cancer relevant T cells.
Recently, we reported a confirmed partial response or PR from the phase one dose escalation part of the Q1 O. One trial for a refractory heavily pretreated patient.
We view this resist confirmed partial response in the monotherapy dose escalation portion.
Of the phase one trial as an important derisking event, providing evidence of the potential ability of single agent Q1 O. One for selectively engage and modulate T cells and a challenging patient population.
While still early in development. We believe this promising data supports the potential of Q1 O one having a registrational path forward.
As a monotherapy in second line and beyond HPV positive head and neck squamous cell carcinoma patients as the drugs mechanism of action is based upon activating HBV E. Seven specific T cells. We also believe this recent data supports the premise that Q1 O one.
They also enhanced patient reach and therapeutic benefit for frontline HPV positive head and neck cancer patients in combination with timber Elysium app.
Mark of Truda, which is currently of standard of care for these patients who have of composites a positive score for.
For our Cps greater than one for PDL expression.
The combination trial referred to as the key note a 78 trial is presently enrolling patients and we look forward of providing an update on this combination study at the next quarterly call.
In summary, we believe that the emerging data from the ongoing monotherapy trial have the potential to be transformative for cue biopharma as it provides objective evidence of clinical activity as a monotherapy and of late stage prior treatment refractory patient population.
We also believe that this day to differentiates our lead drug product candidate cue 101, as well as our drug candidate pipeline from a competing IL two modalities in vaccine programs kind of Matteo will further will provide further details on the compilation of supporting clinical data to date.
So as we continue to generate data in our ongoing phase one dose escalation trial, it's important to recognize that if favorable these data provide risk reduction and validation for Q1 O. One and also by implication the entire IL two based cue 100 series.
This principle as shown on the next slide slide number six.
As demonstrated here on this slide the underlying framework for the IL two based cue 100 series remains essentially the same across programs with the primary difference being the a nine to 10 of amino acid antigenic antigenic epitope in the MHC, our HLA binding growth.
Our second drug product candidate from the cue 100 series of Q1 O two which targets the wilms tumor one protein or WT, one which is an aqua fetal protein expressed in a number of solid tumors as well as hematological cancers.
Which is being developed in collaboration with our Asia territory partner LG Chem.
To expand patient reach and potentially address resistance mechanisms. We've also derivatives. The cue 100 series, providing us with neo stats to address tumor heterogeneity.
And redirected the stats already stats to address resistance mechanisms of HLA loss in tumor immunogenicity.
Importantly, we believe that positive clinical results for Q1 O. One have the potential to provide mechanistic support for the entire cue 100 series of derivative of platforms for.
First the niche will provide an update on one of our drug candidate pipeline expansion and provide an overview of the platform's modularity and flexibility to potentially address both oncology and autoimmune disease.
Following of nieces pipeline update Ken of Matteo will provide a clinical update including a discussion of the recent confirmed partial response.
Through focused execution of our corporate development strategy. We believe we are well positioned to potentially demonstrate the transformative nature of our protein engineering approach to provide breakthrough immunotherapies for patients in need of more effective therapeutics.
With that I'm now going to turn the call over to a niche thanks Dan.
Like to start with the broad perspective on our platform in the evolving pipeline, which should also provide a helpful context to the important clinical metrics of emerging from our current trial with Q1 of one to remind everyone. Slide seven shows you. The overall molecular structure of our IL two based cue 100 series the.
Q1 hundred series was designed with the key focus on the objective that the IL two activating signal was selectively delever the tumor specific CDA T cells. The present, the presence of bi valent tumor peptide HLA loaded molecules.
Which of signal one that's shown here allows for selective targeting of tumor specific T cells. This molecular scaffold is designed to potentially minimize systemic activation of non tumor related T cells, which constitute the vast majority of the T cell repertoire in an individual the.
For IL two molecules are conserved within the cue 100 series and have to keep modifications one abrogated binding to IL two receptor alpha which avoids the bias towards the regulatory T cells or T Rex and minimize the safety liabilities and the second attenuates binding to IL, two receptor beta which favors activity.
Towards the TCR engaged anti tumor T cells that share.
The one previously and will be highlighted later in today's presentation of the clinical data. We have observed Q1, the one selectively activate and tumor specific T cells. We believe this exemplifies the power and potential of targeted versus systemic approaches beside of guidance such as Iot for cancer Immunotherapy. In addition of key strength.
Of the immuno stat platform is its versatility and modularity with respect of swapping different tumor derived T cell epitopes to change the indication of interest as an example, Q1 the one targets HBV <unk> specific T cells, while Q1 O. Two our next clinical candidate for which we anticipate filing of N D. In the first half of 2022.
Targets Wilms tumor one.
As mentioned by Dan earlier.
The majority of the molecular framework, including the IL two molecules are identical between Q1 of the one in Q1 or to the <unk>.
Next slide slide eight provides a more holistic view on the clinical experience of cue 101, and its impact on various pipeline and platform enhancements. We believe that the encouraging metrics for Q1 of one with respect to Tolerability favorable PK and exposure and PD data and now tumor response clinical data support multi.
<unk> therapeutic opportunities as shown here first as mentioned before it is our belief that the immuno stat pipeline of assets, including Q1 O two targeting the Wednesday of a one and the K Ras <unk> Dalian molecules have a reduced risk profile due to clinical observations of Q1 for one second we also believe that the neo stat platform.
Which is a derivative of the IL two based cue 100 series and is designed to address tumor heterogeneity also directly benefits from the cue 101 clinical data to remind you of the neo stat platform allows us to generate the core generic scaffold of the IL two based cue 100 series without of tumor peptide that is an empty stabilized HLA.
Molecule for which the desirable tumor epitopes can be efficiently conjugated. This strategy allows us to target multiple tumor antigens maximizing the timing and cost efficiencies from a clinical application perspective, we believe the current clinical datasets with Q1 O. One provide strong support for neo stats since the core IL two molecule.
And HLA allele remain the same third we also believe that the development of the bi specific redirected immuno stats of ready stats designed to address tumor escape mechanisms of HLA loss of antigen presentation defects also derive benefit from the cue from Q1 of one since the core of IL. Two framework is essentially the same.
We've evolved the ready status based on two key observations one a significant fraction of human cancers up to 30% in some cases will undergo a loss of HLA molecules and the antigen presentation of defects, which makes them essentially invisible to tumor specific T cells and two observations from cellular analysis of human cancer tissues.
Have revealed the significant presence of virus specific memory CDA T cells in the tumor tissue to the.
And by specific ready stats contained the two key components viral T cell epitopes to engage anti viral T cells, along with the tumor targeting arm that allows for binding to a tumor cell surface antigen such as the trove to MISO tea line her two et cetera, and this man of the cancer cell of bound to already start.
As of the virally infected cell, which can be recognized and killed by the anti viral of T cells in the patient.
We believe this approach may provide several unique advantages from a mechanistic efficacy and safety perspective the.
The novel Bi specific format of ready status is very distinct from other bi specific molecules that indiscriminately activate T cells, resulting in systemic cytokine release and toxicities.
Last week at the New York Academy of Sciences Frontier in cancer Immunotherapy meeting, we presented early data, indicating that ready status exhibited equivalent killing of target cells compared to <unk> three by specific molecules, while avoiding systemic activation and cytokines of accretion.
For autoimmune and inflammatory diseases, we have exploited the same IL two variant from Q1 O. One to design of novel first in class molecule for induction of an expansion of regulatory T cells as shown here. This molecule Q4 hundred one contains the two key signals on IL two variant of the TGF beta Varian for the induced T Reg or the I T Reg defense.
The Asian importantly, and in contrast to other approaches focus on the expansion of natural T. Regs. The IL two variant is not biased towards IL two receptor Alpha we've previously presented data, indicating that in in vitro assays Q4 hundred one can induce an expand regulatory T cells derived from L. A the human subjects and for.
Some patients suffering from rheumatoid arthritis, and inflammatory bowel diseases more importantly, these T cells exhibit of suppression of the effector T cells in vitro assays more recently, we have generated additional data in in vivo animal models of both the mechanism of action of Q4 of one and then using an expanding T regs and the <unk>.
Persistence and in vivo activity, we will plan on sharing additional details of these exciting datasets and of future scientific for them in summary of the following slide slide nine outlines of broad vision on the autoimmune front. Our core strategy here is centered on two key approaches.
The allergen specific and part of a specific the antigen specific approach deploys the meter starts to modulate auto reactive T cells in diseases, where the well characterized or few auto antigens such as type one diabetes. In contrast, the pathway specific approach as exemplified by Q4 to one of the previous slide this focus on induction of an expansion of.
Between T cells and the additional tolerogenic pathway for broad applications, we've been collaborating with Merck on the antigen specific approach focused on two autoimmune diseases and have made significant progress, which underscored the extension of our relationship last year to focus on optimizing potential lead clinical candidate molecules earlier. This year, we presented the progress update on these.
We have a presentation at the antigen specific tolerance meeting those data slides are available on our website and as discussed in the previous life book for the path of a specific approach we continue to make strong progress with our lead Q4 to one asset for generation in expansion of regulatory T cells directly in the patient's body, we believe Q4 to one.
The unique opportunity to reset of immune balance for numerous autoimmune diseases graft versus host disease, and even transplant rejection with that summary, I'd like to pass the call to Ken and material to provide a clinical update on Q1 of the one.
Ken Thanks, Thanks, the nation. Good afternoon, everyone. It's all always I'd like to say thank you. The all of the participating for principal investigators their names are shown on the next slide slide 10.
We have noted on previous earnings calls, we have continued to screen and enroll HPV 16 positive head and neck cancer patients to participate in our trial throughout the COVID-19 pandemic.
We have fully enrolled through cord seven of the eight Meg per kg dose without reaching a M. T D. Oar maximally tolerated dose and have now completed enrollment of cohorts five at two milligrams per kilogram and six at four milligrams per kilogram to nine patients each in anticipation.
Of selecting our expansion cohort dose in the near future the.
Next slide slide 11.
Shows a high level summary of the clinical design and dosing cohorts for our for this ongoing phase one trial of cue 101, enrolling second line and beyond patients that are HLA, <unk> positive with recurrent or metastatic head and neck squamous cell carcinoma, driven by H P.
V 16.
We have now completed enrollment in the part a dose escalation portion of this trial.
As I have noted in previous earnings calls this escalation phase of the trial protocol provided the opportunity to dose up to nine patients in any given cohort to provide and bolster evidence of clinical activity or PD effect in the order to enhance our ability to choose the most appropriate.
Dose for the part B expansion and presumed the recommended phase two dose.
The next slide Slide 12 shows some of the details about our enrolled patients to date the van.
The majority of our patients more than 90% have been treated with cue 101 is third line of graded greater therapy. After failing both platinum based chemotherapy and checkpoint inhibitor. Many patients also failed treatment with the epidermal growth factor inhibitors cetuximab.
Several observations give us confidence that our data is maturing to allow us to make an informed decision to choose our expansion dose.
First as shown in slide 13, our data to date demonstrates the tolerability of cue 101 in patients we have treated through cohort seven and eight makes for cash as I mentioned without reaching an M. T D. All of the SaaS and Aes <unk> observed to date are consistent with.
Those that are observed with IL, two administration or typical of those observed with immune modulators and the treatment of cancer patients the.
Most common as observed include fatigue, and anemia and decreased lymphocyte counts.
Second as reported in the previous earnings calls, our pharmacokinetics or PK data as shown in the next slide slide 14 reveals dose dependent exposure without any evidence or effect of anti drug antibodies on PK and exposure and patience then.
Of received multiple doses of Q1 on one.
Third again as reported in previous earning calls the sustained increase in exposure with increasing doses of Q1 O. One has led led to observed pharmacodynamic effects, including early evidence of proliferation of tumor specific CDA positive T cells versus the broader CD eight per.
Positive T cell component, and then increase of natural killer cells or NK cells.
We have previously shared early data on the increase of <unk> seven specific CDA positive T cells and the NK cells in patient blood samples at various time points after dosing of Q1 O. One.
For.
As noted in our previous earnings call as shown in slide 15, histopathology from biopsies of treated patients has revealed evidence of anti tumor activity, including necrosis and T cell infiltration as shown on the left hand panel as well as in the right hand panel evidence of.
PDL one expression on the tumor cells as shown by the Brown staining and the market infiltration of cytotoxic CD eight positive T cells as shown by the pink staining cells.
Fifth in the dose escalation phase of the trial, we have had five heavily pretreated patients patients that received Q1 to one on one of third fourth or fifth line therapy with confirmed stable disease after receiving cue 101.
In addition to the five patients with stable disease as announced last week of patient in cohort six at the four milligram per kilogram dose had of confirmed partial response we.
We believe that the partial responses observed in this patient.
Demonstrating single agent activity of cue 101, something rarely seen in mono therapy treatments.
We believe that this clinical observation provide supporting evidence of Q1 O. One is an active agent with promising potential for HPV positive head and neck squamous cell carcinoma patients, which is further bolstered by the supporting Pharmacodynamic data in which we have observed the activation of disease.
Specific T cells and the NK cells in the blood of our treated patients I will hand, the call over to the Matteo to describe some of these data in greater detail Matteo.
Thanks, Ken.
The next slide slide 16.
Some of the data associated with the confirmed partial response in this patient.
This patient had previously failed cetuximab and Penn for legitimate systemic therapy for their current disease and was treated with Q1 on one as third line for their metastatic cancer.
At the first scan after two cycles of therapy. The patient had an approximate 50 per cent decrease in the size of their target lesions and this was confirmed on their second scan after four cycles of therapy.
The associated Pharmacodynamic data for this patient correlates with the clinical response.
The middle panel demonstrates the slight increase in T. Regs at cycle, one day eight debt returns to baseline by day 15 that we have observed in other patients. Similarly, as we have seen in other patients. We see a marked increase in NK cells on cycle, one day eight debt persist through day 15.
Yeah.
The right panel of demonstrates the nine false increase in E. Seven positive specific T cells and the cycle one day eight peripheral blood sample from this patient.
These data support the mechanism of action of the immuno stat platform.
And supports the further develop meant not only of cue 101, but the entire cue 100 series and beyond.
On the next slide Slide 17, I also wanted to share with you new histology data, which also supports the mechanism of action of Q1 O. One.
<unk> B is the serine protease most commonly found in the granules of natural killer cells and cytotoxic CDA positive T cells. It's the weapon use the utilized by the cells to kill cancer cells Slide 17 demonstrates the biopsies from a patient in cohort five.
Before and after administration of two doses of Q1 O one.
And the post treatment hits, the micro graph on the right and quantified on the graph on the far right. You can see a marked increase in cytotoxic T cells that are secreting granted zone B <unk>.
Providing valuable validating data supporting the mechanism of action of Q1 O. One.
These results are also supported by the preclinical data published late last year in nature methods, where an evening of pet imaging demonstrated that the of course scaffold of an immuno stat, consisting of the peptide MHC components could penetrate solid tumor tissue and directly engage tumor infiltrating lymphocytes.
Hence mechanistically the immuno stats had the potential to directly engage tills and NK cells, which may also altered the local tumor microenvironment to favor antitumor immunity.
As noted in previous earnings calls, we also continue to monitor progression free survival and overall survival of closely and continue to observe what appears to be an enhancement of the survival of patients in the Q1 O one dose escalation trial.
Our clinical trial protocol amendment for the expansion phase will.
Once cleared by FDA, one allow patients to remain on study at investigator of discretion, if they demonstrate radiologic progression, but are clinically stable to.
Add assessment of response by I resist criteria to the exploratory endpoints and third allow for collection of data regarding subsequent anticancer treatments patients may receive to gain further insights into our preliminary survival observations.
I will now hand, the call over to Carrie to discuss first quarter financial results.
Thank you Matteo turning now to slide 18, I'd like to provide a brief update on our financial results for the three months ended March 31st 2021.
The company reported collaboration revenue of approximately $1 6 million in there of <unk> 9 million for the three months ended March 31 of 2021 and 2020, respectively. The ing.
Increase in revenue was due primarily to revenue generated from the extension of the Merck Research program in November of 2020 from which we are receiving additional financial support to further research and develop promising preclinical biologics with the objective of identifying clinical candidates for the treatment of type one diabetes and an additional undisclosed autoimmune disease.
Research and development expenses were $9 8 million of $9 9 million for the three months ended March 31, 2021, and 2020, respectively. The decrease was primarily due to a decrease in laboratory costs and travel related expenses.
General and administrative expenses were $4 3 million and $4 million for the three months ended March 31, 2021, and 2020, respectively. The.
The increase was due primarily to stock based compensation and legal legal fees incurred during the first quarter of 2021 as compared to the same period in 2020.
We ended the quarter with approximately $73 3 million of cash cash equivalents and marketable securities and working capital of approximately $60 8 million in April we extended our cash runway with approximately $10 4 million from the sale of approximately 907000 shares of our common stock under our at the market.
Of the offering true Stifel Nicholas <unk> company, who acted as our sales agents, we believe our cash cash equivalents and marketable securities as of March 31, 2021, along with the funds received in April two of the ATM will allow us to support the development of our immuno stat platform, including the debt clinical development of Q1 of them.
Into the fourth quarter of 2022.
I'll now turn the call back over to Dan for closing remarks and <unk>.
Thanks, Gary.
In conclusion of the car.
The information of clinical activity of cue 101, as a monotherapy in this challenging and heavily pre treated patient population is an important step forward in the supports the potential of not only our cue 101 drug product candidate for oncology.
But for our follow on drug candidates as well such as cue 102 from the IL two based cue 100 series and provides valuable proof of concept of the immuno stat platform to activate and expand disease relevant T cells and NK cells directly in the patient's body as a method to treat all of the cancers.
We anticipate a number of important milestones throughout this year.
With the potential of further data to support the possibility of a registration path for cue 101 as a monotherapy. These.
These milestones include the planned selection of a recommended phase II dose for cue of cue 101 by mid 2021 for further development as the single agent treatment for HPV positive second line and beyond head and neck squamous cell carcinoma.
Our plans to support initial phase one results from the combination study of cue 101 with the <unk> Mab in the second half of 2021.
And our plans to initiate the neo adjuvant study to evaluate the effects of cue 101 on the tumor microenvironment, which is also expected to launch in the second half of of the year.
We continue to execute our corporate strategy and a focused and deliberate manner with the aim of demonstrating clear competitive advantage and market positioning of the immuno stat platform and associated programs.
We believe that cue 101 monotherapy trial for.
<unk> the potential registration path forward as a single agent therapeutic in the combination trial with member Luiza Mab also known as Keytruda provides the prospects to enhance the patient reach and market size by moving upstream for first line patients, where we anticipate the potential for significant mechanistic synergies as demonstrated.
In our preclinical studies, we look forward of providing the trial status update at our next earnings call.
Finally, we'd like to thank our employees, whose dedication to our mission through their commitment and professionalism allows us to continue executing our corporate development strategy, we'd like to thank our board of directors for their support and guidance and want to thank our shareholders, who provide us with the essential resources to continue our important work developing prom.
Missing therapeutic candidates for patients in need.
Most importantly, we want to thank those patients and their families involved in the clinical trials their courage and willingness to be part of the clinical study allows us the opportunity.
To assess potential drug activity and assess the potential therapeutic benefit of our promising drug candidates.
With that I want to thank you very much for your attention and interest I'd now like to turn the call back over to the operator for questions.
Operator.
Thank you we will now begin the question and answer session to join the question queue. You May Press Star then one on your telephone keypad.
Tony acknowledging the request.
If you are using a speakerphone please pick up your handset before pressing any keys.
Your question. Please press Star then two.
Pause for a moment of callers join the queue.
Our first question comes from Tom Shrader from B P. I G. Please go ahead.
Thank you and let me be the first but hopefully not the only to congratulate you on the response, it's been quite a push so congratulations.
I have kind of a general question probably for a niche.
How many patients do you have.
Blood levels of tissue specific T cells and tumor specific levels of the are you getting to a point, where you can start to define the curve as to what levels of the blood might mean in the tumor at least for the specific.
Example, and then I have of T. Reg question, if I can.
Yeah sure. Thanks, Tom so in the data points that we have evaluated so far.
Being able to detect <unk> at about <unk> and about a third of patients and I caveat that by the sampling of times because our major.
Bleed is at day 21 after injection of the drug of day zero. So there is a favorite of the things that happened in the middle of T cells. Once they get activated expansion in extravasation from blood. So we view that as it is of significant positive just by doing these first boss analysis of it remember this is.
Direct detection from the blood with no ex vivo expansions et cetera, we're looking at.
Additional protocols, having said that as you saw here when Matteo presented this was about a nine fold increase we'd also reported I think about a seven fold increase in the patient with the stable prior disease stable disease in the in the prior presentation, we just need to do enough of them have.
Additional data to be able to make any sort of hard conclusions storm, whether these numbers at the end of the day of our correlating with an objective response and I say that simply because of the fact that it's a wonderful reed in the blood for mechanism of action of the BD activity, but ultimately we think have a deeper insights into the target tissue.
You will.
Well reveal more meaningful sort of outcomes and that's been the <unk>.
General narrative in the field as you as you will have followed that all of this was actually one of the reasons why we've pushed for the Neo adjuvant study where.
We have.
The guaranteed access to the blood and the tumor tissue post surgical resection pre and post Q1 O. One administration. So I think the blood data is fascinating, it's very positive from a BD perspective, but I think as we go through the rest of the year and start gathering the metrics from the Neo adjuvant study will hopefully be able to strengthen and make those correlations.
<unk> the man the the biopsies of the current trial.
Mandatory as Youre well aware of these are optional so we're very grateful and thankful to patients that have provided us those although they have been.
Fewer events, there, but nonetheless, the data that can presented and Matteo discussed the just fascinating to see the immune effector mechanisms sort of start to kick in after the drug is administered.
Okay, and then quickly on the T. Reg program your RNA data is presumably.
Our model, where you know exactly the antigen do you think of the disease like RNA Ara you will need exactly the the T. Reg antigen or can it be one of several and you just get enough T regs in the joint.
You would have some sort of an anti inflammatory effect of any data there yet.
Yeah, No I'd say, it's a fantastic question, Tom so in especially in the cases of chronic autoimmune diseases like RA like lupus like IBD, where the diversity of antigen is vast and its not well characterized it in sort of in many cases I think having this Q4 hundred one asset is extremely beneficial because it expands.
The direxit globally and the hope is that they would then.
But turnaround in modulating control auto reactivity in fact, that's what has been seen and that's what we've seen in the role in vitro assessments of activity of the cells that is in contrast to the immuno stats, we're deploying with Merck in the collaboration for example for diseases like the Wendy with focused antigens like pro insulin in that case, but those diseases.
Handful, where some of those antigens are really dominant of well characterized but you're absolutely right. That's exactly the reason why we had this dual strategy of an outage in specific the deploys immuno stats and pathway of specific that's actually agnostic of the outage of identity and goes after the the bus regulation of the potential of T. Rex.
Alright, great. Thank you and congratulations again.
Okay. Thanks, Tom.
Our next question comes from Mark Breidenbach from Oppenheimer. Please go ahead.
Hey, good afternoon, and let me add my congrats on the progress of them, especially on the partial response, that's great news.
I was wondering if you could tell us a little bit more about the responding patient.
Whether or not they were high.
Hi, Mary refractory to Pembroke, whereas this was the case of the acquired resistance and also how long the patient had been off Pembroke before we see day in Q1 O. One.
Ken do you want to take that question.
Yeah.
So.
These patients all of the patients virtually have been on some kind of the checkpoint inhibitor in this patient sales hambro.
And it's controversial of how long.
No.
How long the temporary sort of hangs in the system.
What I think we can say for sure.
With a confirmed PR 12 weeks into treatment that there wouldnt be any <unk> in the system.
So the patients still on study and so I'm hesitant.
Moving to report too much more about about the patient, but we will be happy to share that.
And later.
<unk>.
Okay Fair enough and one quick follow up just on the really nice biopsy he showed us.
You were able to collect paired biopsies from from the responding patient.
I'm wondering if we can expect to see an analysis of of pre and post treatment TCR sequences from inside the tumor infiltrating lymphocytes.
The initial take that yes, so that has been an area of very high interest for us as you well know in previous sort of studies.
The studies, we have done a fair bit of single cell TCR analysis in express and that's exactly the intention here is to get to a point, where we can using the single cell platforms identified per TCR of express them and then not only show of functionality to for the E. Seven of epitope, but also show a clone analogy for all of the clonal expansion.
Or data that we've previously reported with immuno stats in preclinical models of ex vivo expansion that is the very intention we intend to do with the clinical samples and in fact again coming back to the Neo adjuvant.
The Mark that's one of the major goals there is to be able to characterize the tests with response to both commonality and specificity.
Okay, perfect working for it to it and congrats again on the data.
Thanks Mark.
Our next question comes from Ren Benjamin from JMP Securities. Please go ahead.
Hey, guys, congratulations as well on the it's true for clinical news a couple of questions, maybe just starting off with the patient and patiently for Ken can you talk a little bit about prior to entry into the study was the was the patient you know progressing quite rapidly was he.
The relatively stable or slowly progressing.
Mentioned that he's still on the on the study of the overall.
Overall I don't know if you could make any comments what is he doing doing fine.
And I guess related to that is this the highest CDA T cell count that you've seen to date peripherally or where there are other instances, where we saw higher levels.
[noise] well.
Let of niche comment on the C D eight levels, but.
The patient does remain on study.
And it is feeling you.
Clinically well.
And what I'll say is you know the.
The patients progress.
And rates of progression I guess of relative term.
The Kansas grow in and that's not good and so the the.
The patient went out of the study.
I think because of the patient is still.
<unk> B is still active I really would like to hesitate to go into a lot more detail about the patient.
And then just to add on of the T cell increase we have seen T cell increases remember there is a small increase rents of its driven by the denominator of what you'll find initially but I do want to caveat that again by sampling in fact, one of the major amendments that were trying to accomplish and that kind of material of driven is to get more blood samples.
At the time points of we can understand the kind of ethics to be able to get deeper insights into this but this is an area where we have noticed the.
The sort of fold expansion in this range even in the prior samples.
And again.
The knowing whether debt as opposed to what we've done in preclinical models, where you can sample or the more regular basis and understand the kind of medics of engagement expansion and contraction.
That obviously is limited what you can do with patients and the situation.
Hopefully we got the more insights as the data continues to mature.
But nonetheless, it's extremely positive to see these red frequencies just emerge in the primary snapshot that we have been able to detect them.
Okay fair enough as we think about the recommended phase two dose can you just kind of talk us through maybe the the matrix here of what you are considering one of the metrics that are going to drive.
That decision.
You have the nine patient set of enrolled whether you see additional responses I think then the decision becomes easier if you don't what what what other factors and what else do you need to see to declare a recommended phase two of us.
Yes can do undertake that.
Yeah, Thanks, well.
It certainly becomes the totality of the PK data the PD data the clinical responses as well as the.
The safety data.
All of which is maturing.
The literally as we speak for the the later cohorts.
And I do believe that.
We will have the data we need.
To choose that dose.
Within the next month or so.
Got it okay.
And then I guess, just one final one for me probably for a niche.
Could you give us the.
That's the how the the two programs the <unk> TGF beta in the in the mud programs are are progressing in the.
In the autoimmune problem.
Yes, sure so on the Merck side with the antigen specific approach the teams focused with the provincial and specific immuno stat for type one diabetes, we have made tremendous progress there.
One of the thing that molecule towards the potential lead clinical candidate and we are aiming to have those studies completed by the end of the year on the this fascinating Q4 hundred one this is a fantastic asset of this this is really exciting for us because of the breadth of application. So we've generated foundational data, we actually have been invited to focus.
We will be presenting of talk on this in June as well.
For the intentions of the continue to validate in preclinical models have that solidified by the end of the year to be in the position to start initiating IND, enabling studies et cetera, and position ourselves to start thinking about what the clinical development strategy would look like.
For chronic autoimmune sort of so the big indications, but talking about already in IBD, and lupus etcetera, which stand out to us.
Terrific. Thanks, very much for taking the questions.
Okay. Thanks, Ron.
Our next question comes from Stephen Wiley from Stifel. Please go ahead.
Yes, good afternoon.
Congratulations on the progress.
Good day.
I know in your prepared remarks, Dan I think you kind of re emphasized your confidence in monotherapy.
Of potential Registrational path forward.
How are you guys thinking about pursuing that as of right now and I guess should we anticipate.
Because of this I guess, it's extended of bad times that you're seeing in patients that.
The trial in the setting would most likely be something like Q1 of the one versus best supportive care.
Salvage or do you think if you've seen other response or two just given I think the low single digit response rate that's associated with current standard of care do you try to push forward in a single arm study.
Yeah, I'm going to just answer that broadly, but I'll hand, it over to Ken as well.
I think you actually just summarize the answer to it and that that's how we're looking at these patients as you know of refractory. There is no standard of care of many of them are basically going on palliative.
Therapy, So I think one it's looking at the response rate.
Another couple of Prs in the I would really bolster confidence.
We're confident by what we're seeing already to date in that we're seeing the molecule is actively modifying the relevant immune components.
We are seeing.
Again in a dose escalation, we sort of five confirmed stable disease of confirmed a par.
For response.
As a mono therapy, and we're seeing what appears to be emergence of data, suggesting as the survival advantage. So all of this is basically giving us confidence going forward and it will be continuing that type of data.
Give us confidence going forward with the registration path, but with that I'll turn it over the counter if he wants to elaborate.
Oh Wow.
I think you said it well the Bottomline is is if we.
We think that we have a registration path is a single arm study, that's certainly what we're going to pursue them.
Yes.
I'll leave it at that I mean, that's what we're hoping and that's what the data looks like is emerging.
So in terms of the monotherapy expansion cohorts at the recommended phase two dose do you then I guess have a conversation with FDA and potentially design that such that those phase one expansion patients could be enrolled into a registrational dataset.
Short answer yes.
Understood.
And then maybe just a bigger question here.
You know you've got proof of concept of established with the cue 101 series in.
You've got a lot of other interesting the construct that you're working on.
D O stat in the ready stats, but.
How do you just think about prioritizing each of the opportunities now within the pipeline because of the Derisking I guess I'm one of the one you try to accelerate the WT. One do you accelerate K Ras can you accelerate both of those things in the context of making progress on these construct some of the novel formats, how do you guys.
Think about that.
It's a it's a complex question Steve as you know is it has to do with the resource.
Access our resource allocation priority right now is.
Focus on establishing a foothold or a beachhead with 101, which by implication applies in terms of Derisking and validation to the 100 series.
So we have 100 to 101 102 and went out for partnered with LG Chem.
So.
A strategy that incorporates the potential of.
Looking at Ah patients.
Patients here in the U S as well as Asia Thats.
That's something we consider.
So I don't know if there's one priority I think all of it is actually who are the important. So we have to continue pushing forward with 101 as establishing the foothold within expanding out into 102 to make sure. We're doing that in the timely manner right now we're expecting the IND to be filed.
In Q1 of of.
2022.
And K Ras is obviously a high profile program.
So where we're putting our resources on that as well going forward beyond that it's really going to be based on resource access and allocation, but right now it's really focused on establishing the foundation of principal with 101 and expanding out as efficiently as we can with the other programs.
Understood. Thanks for taking the questions.
Yes. Thank you.
Our next question comes from Brian <unk> from Baird. Please go ahead.
Hey, good afternoon, everyone of Dalyell nail for my congrats too on the single agent activity.
It seems like it's really sports a lot of immuno stat platform and probably in particular, the the 100 series so to that point I guess how.
How do we kind of think about using the 101 monotherapy in thinking through the design of our phase ones and K Ras and Williams.
Does this give you any opportunity to sort of accelerate growth through dose escalation here, maybe starting at a.
Total debt that would be closer to what you think would be relative exposures for driving response in the T cell activity.
Yeah.
Ken do you want to take that.
Yeah.
Great question the.
We certainly believe that.
What we've learned from 101 has will allow us to.
Proposed to the FDA that we'd be able to start it for.
For example of higher doses.
Then we were with cue 101.
And.
We have that as part of the R.
Our pre IND meeting question set of questions is is will the FDA accept the.
The learnings from Q1 on one as part of what we do going forward. So.
I would also mentioned that.
Yeah, we really like this trial design that we've used for one on one of.
Which is based on the three by three.
The design, but also lets us backfill cohorts as needed. So I think we'll use that strategy again.
We will be able to.
Get to clinically relevant doses much quicker based on.
The PK PD and safety data that we've observed with one on one.
Great and then maybe digging a little bit on the on the 101 PD data.
Is there anything on the PD side that shows kind of a clear dose relationship you did the increase of NK cells are under the seven specific CDA T cells I'm, just trying to get a better dose dose level of passenger who really don't see this activation like cohort three and as the dose level, where you sort of see of peak out in higher doses, maybe cohorts all of them.
Just arent showing any additional act of it.
The initial.
Brian So for you if you look at some of the emerging BD metrics, including some of the MK data leasing the cohorts five and six you start to see the uptick at about cohort three and for but at five and six they're very comparable so we think these.
Youre looking around activity appear to be very relevant cohorts. It's also what Ken and Matteo stressed as you've heard about the dose expansion. We just have to mature on the T cell side with some of these emerging metrics and I think something more would help.
Obviously make the continue to make this a strong but already with what we're seeing with the sustained increase in encase the the.
Notable sort of the increase.
The increase in the E seven specific.
The only of transient uptake on T. Regs that comes back for the based on I think provides a very strong case that these are you know these.
These appropriate cohorts of that seem to exhibit what we would you know book.
Some of the indicated is very relevant PD metrics for us to be able to move forward on.
Great. That's helpful. Thank you.
Yeah My pleasure. Thank you.
Once again if you.
Have a question. Please press Star then one.
Our next question comes from Xinjiang true from Darrin Baird. Please go ahead.
Hi, good afternoon.
Thanks for taking my question I wanted to add my congratulations to the routine the swaps.
And thank you for the first ask about the safe the I know it looks like the safety is quite favorable.
Curious for the legal site decrease.
One of the idea of Hawaii, but we've seen some green.
Three of them signed.
A decrease of one.
It wouldn't be.
The O too.
Of course to be designed to activate T cells in.
And then T cells in this manner.
So Ken Ken do you want to comment on that of I can follow up off to Ken.
We'll go ahead of any.
So the.
Again the.
The activity of IL two of them peripheral lymphocytic populations, including in piece of the encase post activation as Youre well aware.
The raise it.
It's been noted for the Extravasation you see these trends in the dips I think that likely explains of these active doses is the most likely aspect.
And consistent with what's been sort of scene.
Prior of pharmacological measurements.
Okay, Yeah yeah.
Yes.
It's a known IL two effect.
Essentially what it is.
<unk> represents is the IL two moving out of the lymphocytes moving out of the blood into tissue and the non specific manner and at those early time points.
Got it okay, Alastair and and then.
I also wanted to ask about the the combination trial.
The one in Q1 O one.
Based on your preclinical modeling.
Have you seen the synergies between them.
Yes have you observed PDL one being operating later in the Q.
Q1 of one treatment.
So I can take that at least from the preclinical side Z, which is a very important component of that not only supports but provides a lot of good evidence for the logistics of first of all.
As everyone appreciates the checkpoint blockade like PD one in the absence of the right repertoire is likely not very meaningful. So the fact that Q1 and one of the lists and activates the repertoire is actually.
Very meeting for from that end.
In our preclinical studies that we published last year in clinical cancer research.
The E seven driven aggressive <unk> tumor model <unk>.
We saw monotherapy the mean.
During Q1 of one surrogate its activity, whereas PD one alone in that setting was no better than the vehicle. However, when that monotherapy with them for the combined with anti PD one blockade in that model.
The substantial increase in the observed efficacy in response in the animals upon closer examination of the tumor tissue from those out of the moves we could again very nicely located tumor specific T cells in both mono and combo, except that in combination therapy those numbers.
No.
President of high end numbers within the tumor tissue and as Ken showed you from the histopathology of the one of the patients.
In his section we have observed and this is from a more of a trial, where the tumors are expressing PD like an end of infiltrated by CDA T cells. So putting it all together I think as we continue to build on our combination trial.
All of that data combined with what we've noticed preclinical proof of in preclinical.
One of the observations, who should really bode well and further sort of build.
The favorable parameters for these patients.
Okay, Great and the final one final question is the balance you'd probably Oscars one for you.
For Neo Stat ice.
I understand it is a it is empty MTA HLA kind of strapped with IL two.
So I guess is it designed to bind to any PCR and regardless of what true.
The the tomorrow and so on debt.
So the whole concept of the Neo Stat Z is to have the scaffold to which we can then conjugate any tool of peptide, which we do using chemical conjugation using established chemistry. So it's a covalent linkage. So when the drug product actually gets made it's not an empty HLA, but rather it's conjugated with the disc.
Variable epitope of epitopes in cases of multiple antigens and that's quite significant when you compare it to in the immuno stat, where each one of the epitope of like the HBV E seven or the WT. One is the fused peptide. So in other words each one of those antibody molecules is a separate drug molecule with the separate cell line for production.
And the time that with Neo Stat, you have one cell line that can generate the scaffold that can then so many different areas of interest in the indications based upon the tumor epitopes that once the conjugate. So it's still very much antigen specific except that that the versatility of modularity that since it's empty allows us to go after many dip.
Current tumor T cell epitopes and the fact that it's the single cell line, obviously has significant implications for the time and cost to the clinic, it's essentially an off the shelf scaffold that one can deploy in real time to drug for patients that was our vision. When we started on the there's about three years back.
Okay, so essentially for cancer vaccine.
Turbocharged in Ireland.
It's a vaccine in terms of specificity every single vaccine is dependent upon the APC actually doing his job of nitrogen processing presentation. The.
<unk> kind of membrane interactions costumes et cetera, we've just by bus all of that and that's a big leap in the space of immunotherapy.
Got it that's very helpful.
Thank you for it.
Okay. Thank you very good.
Once again, if you have a question. Please press Star then one.
This concludes the question and answer session I would like to turn the conference back over to Dan for the theory for any closing remarks.
Yes.
Thank you everyone for your attention and interest and we look forward of providing a periodic updates as we continue to make progress on these important observations and findings. So thank you and.
We look forward to catching up sometime soon in the near future.
This concludes today's conference call you may disconnect. Your lines. Thank you for participating and have a pleasant day.
Okay.
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