Q4 2020 Cue Biopharma Inc Earnings Call
[music].
Greetings and welcome to cue Biopharma fourth quarter, and full year 2020 earnings call. At this time all participants are in a listen only mode. A question and answer session will follow the formal presentation.
If anyone should require operator assistance during the conference. Please press star zero on your telephone keypad.
Please note. This conference is being recorded I would now turn the conference over to Dr. <unk>.
<unk> Vice President of IR and corporate development. Thank you you may begin.
Thanks, Jerry and good afternoon, everyone. Thank you for joining us on today's call are Dan necessary cue Biopharma CEO, Dr and niche Suri, President and Chief Scientific Officer, Dr. Ken Pienta acting Chief Medical Officer, Dr. Matteo <unk> Senior Vice President of clinical development and Kerri Ann Millar.
Chief Financial Officer.
Before we begin I would like to remind you that various remarks that the company makes during this call about the company's future expectations plans and prospects constitute forward looking statements for the purposes of the private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed and the risk factors section of the company's annual report on form 10-K filed with the SEC on March nine for 2020, one as well as other filings made by the company with the SEC from time to time, which can be accessed on.
Edgar database and W. W. W. W. Dot FCC Dot Gov and in addition, any forward looking statements represents the company's views only as of today March 16th 2020, one and should not be relied upon as representing the company's views as of any subsequent date, while the company may elect to update these forward looking statements at some future point the.
Company, specifically disclaims any obligation to do so.
Even if the company's views change.
Please be advised and 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'd like now I'd like to turn the call over to cue Biopharma CEO Dan Okay. Thanks George.
Afternoon, everyone and thanks for joining us today for a review of our ongoing progress as well as our fourth quarter and full year financial results, which are available in more detail and our form 10-K filed with the SEC on March 9th.
Our agenda for today's call is shown on the next slide here at slide three.
I'll first be providing a brief overview of our corporate objectives and program progress and will then turn the call over to Dr. Ken Pienta to provide a status update and review of our current observations from the ongoing Q1 O one trial.
Ken will be joined by Dr. Matteo Lover City, who recently joined cue Biopharma as senior Vice President of clinical development Matteo brings a great deal of clinical development experience with Immunotherapies and we're pleased to have him on our team.
After Ken and Matteo speak Doctor and <unk> will provide a progress update on our IL two based cue 100 series and its derivative programs Neo stat and the recently introduced a novel bi specific RDR stat, all we referred to as ready stats programs designed to address cancer heterogeneity and <unk>.
Tumor escape mechanisms and niche will also update the recent progress and our autoimmune disease programs and pipeline, including the addition of the Q4 hundred series, a new series that differentiates and expands regulatory T cells for addressing diverse autoimmune indications with unknown or poorly character.
Horizon Auto antigens, Kevin Miller will then summarize our financial status after which I'll return for closing remarks.
First I'll begin with a brief overview of the progress we've made towards the achievement of our stated corporate objectives.
As an overarching theme as depicted on the next slide number four we aim to restore immune balance by modulating the activity of disease relevant T cells directly and the patient's body.
This is a central pillar upon which our entire pipeline of immune modulating programs is based we believe our proprietary immuno stat platform will allow us to harness the fullest potential of and individuals' intrinsic immune cell repertoire for restoring immune balance and thereby help while avoiding the <unk>.
The side effects of broad immune stimulation or suppression.
In addition to the selective modulation of T cell activity, we believe immune.
Immuno stats offer several key points of differentiation over competing approaches, including modularity and versatility to provide broad disease coverage standard manufacture ability and convenient administration.
And important foundational aspect of our development strategy is to utilize the ongoing clinical trial of cue 101, not only to define a potential clinical registration path for the drug candidate per se, but also to generate a representative safety and efficacy dataset potentially applicable in PAH.
Principle, so the entire cue 100 series.
And as the underlying framework for the IL two.
Based cue 100 series remains essentially the same across programs with the primary difference being a 9% to 10 and amino acid antigenic epitope, and the MHC or HLA binding growth and by implication and the clinical results for Q1 O. One may provide mechanistic support for the entire series.
To this point, we now turn to the next slide slide number five.
As depicted we have exploited the IL two based cue 100 series to further design and develop additional drug candidates with variations of the epitope.
On the immuno stat framework, such as WT, one and just wilms tumor one designated as Q1 O two or K Ras G 12 Z.
And to expand patient reach and potentially address resistance mechanisms. We've also derivative is the cue 100 series, providing us with neo stats to address tumor heterogeneity.
And redirected immuno stats already staffs to address resistance mechanisms of HLA loss or tumor immunogenicity and.
In addition, and not shown on this slide we've also utilize the frameworks modularity to engineer and munis to asphalt antigen specific inhibition of auto reactive CD four T cells via PD L. One for treating autoimmune diseases and this is the the cue 300 series with.
And with known auto antigens, such as <unk>.
Immunogenic proinsulin epitope for the treatment of type one diabetes and this is currently being developed and our collaboration with Merck.
We've also deployed the engineered IL two variant from the cue 100 series to design a first in class Bispecific molecule possessing both IL, two and a TGF beta.
Portion. This is referred to as the Q on Q4 hundred series for pathway specific mob modulation for stimulating induced T regs or I T regs to address chronic autoimmune diseases, where the auto antigens are unknown or not well characterized and east will elaborate upon these various developments during his.
Section of program review.
Yeah.
Through our focused efforts throughout 2020, we believe we are well positioned to demonstrate the value proposition of immuno stats as potential breakthrough immunotherapies in the coming months and throughout 2021 with that I'd now like to turn the call over to Ken to provide a summary of our clinical observations with Q1 O one Ken thanks.
Dan and good afternoon, everyone as always I'd like to say, thank you to all of the participating principal investigators and their names are shown on the next slide slide six throughout the COVID-19 pandemic, we have continued to screen and enroll and enroll HPV 16 positive head and neck cancer patients to participate.
And our trial.
We have fully enrolled cohort seven and are currently expanding up to nine patients and each of cohorts five and six and as we focus in on the selection of our expansion cohort dose. The next slide slide seven shows a high level summary of the clinical design and dosing cohorts for our ongoing phase one trial of cue one O.
And one enrolling second line and beyond patients that are HLA O to O one positive with recurrent or metastatic head and neck squamous cell carcinoma, driven by HPV 16.
To date 33 patients have been enrolled was 31 and 33, having previously failed both platinum based chemotherapy and checkpoint blockade and.
And therefore entering the trial, receiving and Q1 on one is third and fourth or beyond lines of treatment for their metastatic disease.
As I've noted in previous earnings calls the second part of the trial protocol provides the opportunity to dose up to nine patients in any given cohort, where we see evidence of clinical activity or PD effect and order to enhance our ability to choose and appropriate dose for the part b expansion and the presumed recommended.
Phase two dose if we had no evidence of dose limiting toxicity, while simultaneously seeing evidence of dose dependent and PK plus evidence of agents specific P. D plus evidence from clinical effect and this is exactly what we have observed to date since the last earnings call, we completed and.
Momentum cohort seven and eight milligrams per kilogram of cue 101, without reaching a maximally tolerated dose or M. T. D. We are now expanding cohorts five and six with the expectation that we will choose the expansion dose and the next quarter.
Several observations give us confidence and our data is maturing to allow us to make an informed decision to choose our expansion dose.
First 33 patients in cohorts one through seven and have received over 100 infusions of cue one on one three weeks apart without reaching and M. T D. Even though we are still on the dose escalation phase of the trial. We've already had five heavily pretreated patients demonstrating confirmed stable disease after receiving <unk>.
One on one.
All the all of these patients who received two one on one is third and fourth or fifth line therapy.
We also continue to monitor and progression free survival and overall survival closely and continue to observe what appears to be and enhancement of survival of patients and the cue 101 dose escalation trial, while it's still early and part of the dose escalation study. The overall survival of these patients is encouraging and continues to be.
Monitored closely because as a reminder, overall survival is the primary endpoint for FDA approval and oncology.
Second as reported and the previous earnings call. Our pharmacokinetics data reveals dose dependent and exposure without any evidence or effective anti drug antibodies on PK and exposure and patients that have received multiple doses of cue 101, and third the sustained increase and <unk>.
Exposure with increasing doses of Q1, and one has led to observed pharmacodynamic effects, including early evidence of proliferation of tumor specific CDA T cells versus the broader CDA positive T cell compartment and.
And an increase and natural killer cells or NK cells.
We've previously shared early data on the increase of 87 specific CDA positive T cells and patient blood samples at various time points dosing of after dosing with cue 101.
The next slide slide eight shows and additionally, it shows additional PD data that point to a dose dependent notable increase of NK cells and circulation eight and 15 days post the first dose and Q1 on one.
The increase of and NK cells as evidenced starting at around cohort three and becomes more pronounced and the higher dose cohorts and especially cohorts five and six.
In addition, we also see a transient increase and Fox P. Three positive C. D for <unk> positive T cells, presumably T. Regs. However, in contrast to NK cells and they continue to demonstrate and increase at day 15. The T. Reg population returns back to baseline levels. We.
We believe the notable increase and NK cells and the transient effects on T. Regs are both likely in response to the IL two component of Q1 on one.
Let me now show you a representative example of a patient that summarizes these observations and the next slide slide nine shows a patient that had failed local therapy, and then failed therapies with chemotherapy, plus cetuximab and as well as member Luiza Mab for recurrent disease.
Notably the patient had progressive disease with a 9.4 weeks on the prior regimen of Pembroke.
The patient was then treated with Q1 on one as third line therapy for their metastatic disease and remained on study with stable disease for over 18 weeks.
The next slide Slide 10 shows the PK exposure for the data for this patient which was dose proportional across all cohorts as well as the observed increase in east <unk> specific T cells and their cycle five day, one blood sample slide 10 also shows that the patient had stable disease for 18 weeks ordinarily.
Doubled their time on a checkpoint inhibitor.
Furthermore, it is important to note that this patient did not have progressive disease and came off study for off protocol reasons.
And anecdotally as shown on the next slide slide 11, but characteristic of additional recent data is a biopsy of the of the lesion from this patient taken shortly after the end of treatment when the patient was off protocol.
This biopsy revealed evidence of anti tumor activity, including necrosis and T cell infiltration as well as evidence and PDL one expression on the tumor cells as you can see on the slide.
Of note. This is a cohort four patients treated at one milligram per kilogram Q Q1, and one which is the starting dose for the combination study with member Luiza Mab and the first line recurrent or metastatic head and neck cancer study.
The next slide Slide 12 shows. Another representative example of a patient that we believe demonstrates an effect of tumor Q1 on one on tumor lesions and tumor lesion size. This cohort five patients had most recently failed and if all the mab another checkpoint inhibitor after <unk>.
Eight weeks on therapy, the patient required COVID-19, and came off study, while still with stable disease. After 28 weeks of therapy with Q1 on one day.
The next slide Slide 13 shows that this patient had three target lesions, we were monitoring radio graphically.
And the first scan after seven and a half weeks and after receiving two cycles and Q1 and one there were variable observations with one lesion remaining unchanged from baseline one lesion growing modestly by about 8% and a third lesion growing to 18 per cent just under the 20 per cent allowed prior to designation.
Progressive disease is important to note regarding this patient that went with the next scan six weeks later it was observed that the lesion, which had shown the largest degree of growth and that first skin had a significant reduction on the second scan and it goes back to baseline on the third.
Our data is showing initial tumor growth and then reduction is similar to observations by others and the evolving Io field supporting the premise that it may take more time to see responses with immunotherapies, such as Q1 on one as compared to classic cytotoxic therapies.
Yeah.
So the totality of our findings to date, including the representative data just presented has led us to draft a clinical trial protocol amendment that will allow patients to remain on study and investigator discretion. If they just demonstrate radiographic progression, but are clinically stable this will provide.
The physician investigators the opportunity to give patients who may be responding clinically that is feeling better, but whose scans and do not yet show radiographic response, the further opportunity to assess potential benefit from Q1 on one.
We're also amending the protocol to add measuring response by I resist criteria to the exploratory end points, reflecting the evolving nature of activity and responses in the Io field overall.
Furthermore, as Q1 on one is an activator of the immune system, it's clinical beneficial effects may still be observed in patients. Even after they have ended there per anticipation in our clinical trial as such we are also amending the protocol to allow collection of data regarding follow on anti cancer treatments.
The patients may receive to gain further insights into our survival observations.
The next slide Slide 14 shows our collaboration with Merck for keynote 878 are frontline therapy phase one trial to evaluate Q1 on one in combination with Pepper Elysium advocate truda for patients with HPV positive head and neck cancer, who are also HLA O to O one positive the first.
Patient at the cohort for Q1, and one dose of one Meg per kg and Keytruda dose of 200 milligrams per kilogram every three weeks has been successfully dosed on this trial and several more patients have been and and are being actively screened for enrollment.
The next slide slide 15.
Reviews, and reminds us of our preclinical published results showing that the combination of cue 101, and an anti PD. One antibody resulted in significant anti tumor activity as noted by the purple line on the left as compared to either agent alone. This activity was accompanied by significant.
And increases and E seven positive T cells, and the blood as well as the tours and the tumors of mice shown and the right panels.
Our enthusiasm for our findings to date and bolts bolstered our confidence and the promise of Q1 on one as a monotherapy as well as in combination with Pembroke and the.
And the recent recruitment and a doctor Matteo 11th Saudi as senior Vice President of clinical development underscores our confidence of the recent progress and our ongoing clinical trial and Dr. Lots of Saturday brings a wealth of experiment experience and the development of I O agents from phase one to Registrational phase III clinical trials over.
The next quarter Matteo plans to expand the clinical operations team to support the phase one day expansion the combination phase one a one b trial and the Neo Adjuvant studies, we have described in previous earnings calls.
Personally excited about our progress and pleased to welcome Matteo on board as our partner and developing Q1 on one as well as and shepherding. Our next Q agent and Q1 O two through the eye and the process I will now hand over the call to Matteo to say a few things.
Thanks, Ken I am delighted to join the queue team at this exciting juncture of the company's continued corporate evolution.
My own background, and training and clinical medicine, and immunology, coupled with immunotherapy drug development experience at Merck Roche Pfizer and several biotech companies have provided me I believe with a solid foundation and breadth of experience that I'm excited to deploy to lead queues clinical development pipeline.
And to help map the future vision and strategy.
From a personal immunological perspective, I think the science that you and Dan outlined exemplified the potential for broad utility and application of the core technology platform, both in immuno oncology and autoimmune diseases.
The data emerging with clinical observations of the IL two based cue 100 series B of Q1 O. One has the potential to open up many untapped opportunities and immuno oncology. In addition, the progress and auto immunity, both with the antigen specific approaches, but also with the more recent development pathway specific therapy.
Strategies to induce and expand regulatory T cells are exciting possibilities for patients suffering from chronic autoimmune and inflammatory diseases. These.
These opportunities are selectively modulating the immune repertoire in and immuno oncology or autoimmune disease are really exciting from a physician's perspective.
And that's what essentially brings me here I am delighted to be with this team and with this company I will now hand, the call over to our niche to discuss other advances and our pipeline and platform.
Thanks, Matteo Thanks, Ken and I would like to emphasize the key observations that Ken presented and the previous section that have a significant impact on the evolution of the broader pipeline of assets and immuno oncology. Most importantly, the safety Tolerability and the observed clinical activity of cue 101 gives us bolstered confidence with the <unk>.
The buildout of the IL two based cue 100 series as shown on slide 16, the core framework as you appreciate of the 100 series is conserved with respect to the IL two composition. The primary difference really swapping up the T cell epitope to change the target indication to this and we've continued to make very good progress with the immuno stat pipeline assets the target antigen.
Like wilms tumor one WT, one and the mutated K Ras and <unk> 12 to Bally and peptide that has been well characterized by prior studies. We've recently presented these data, including most recently at the Io 360 meeting last month Q1, or two which is our next clinical candidate targeting wilms tumor one is slated for a 90 filing and the first half.
Half of 2022, all our IND, enabling activities are currently in progress and on track to meet this timeline.
Like to do now focus on slide 17, as shown here to address tumor heterogeneity and we've been developing the neo stat platform to target multiple antigens or even personalized neo antigen to remind you of the neo stat platform allows us to generate the core generic scaffold of the IL two based 100 series without a tumor peptide and otherwise this is and <unk>.
<unk> stabilized HLA molecule, two which are desirable tumor epitope can be efficiently conjugated. This is in contrast to the classical immuno stats were on each tumor epitope as a part of the fusion protein and hence each therapeutic molecule requires a separate cell lines for generation of the clinical grade material. So from a functional biology perspective the neo.
<unk> and immuno stat and molecules are very comparable as shown on the graph on the right with examples of T cell expansions from human blood involve and two different antigens CMV and Mark one and either case. The degree of T cell expansion was very similar between the immuno stat or the neo stat from a clinical application perspective, the current clinical datasets with 100.
And one provides strong support for neo stat since again, the core IL, two and HLA scaffold remained the same.
The next slide slide 18 highlights and equally important derivative of the immuno stat platform, which is aimed at addressing tumor escape mechanisms involving loss of tumor antigen and processing and presentation components, including the loss of HLA molecules are notable fraction of human and.
Kansas upwards of 30% and some cases will undergo loss of HLA molecules, which makes them essentially invisible to tumor specific T cells. This escape mechanism presents a significant challenge for therapeutic approaches focused on enhancing anti tumor T cell immunity. These include checkpoint inhibitors TCR T cell therapy approach.
And as tumor vaccines or even classical immuno stats and our approach to addressing this escape mechanism takes advantage of related observations from cellular analysis of human cancer tissues, revealing the significant presence of CDA T cells that are specific for viral antigens, such as EBV flu CMV.
In other words, a fraction of the protective memory anti viral T cell repertoire localized to the tumor tissue likely and response to chemotactic signals that are agnostic of the specificity of the T cells. A couple of the seminal papers highlighting these findings are actually noted on the slide these observations actually presented and net.
Tractable opportunity for us to leverage the 100 series to generate and novel class of bi specific therapeutic molecules as shown on the slide to redirect or trick the vouchers T cell repertoire to kill the cancer cells, including those that have lost the expression of HLA molecules. We call. These new class of bi specific molecules.
<unk> directed immuno stats, our Rds, that's already stats, but ready status are essentially virus specific immuno stats, but contain a tumor targeting <unk> that allows for binding to tumor cell surface antigen, such as a drop to her to mesothelioma et cetera.
And thus in this manner the tumor cell coated with already stat molecule appears like a virally infected cancer cell, which can then be recognized and killed by the anti viral T cells that populate the host and the human tissue. We believe this approach has several unique advantages it circumvents the tumors lack of HLA or antigen presentation.
And harnesses, a preexisting robust anti viral T cell repertoire within the host it's an opportunity to alter the tumor microenvironment, we're localizing and active immune response from a safety perspective. This approach is very distinct from other bi specific molecules that indiscriminately activate every T cell and also result and sister.
I'm excited and released and toxicities and most importantly, it leverages the clinical observations provided by cue 101, especially as it relates to the IL two molecules and I'd.
And I'd like to now move to slide 19 to provide you an update on the autoimmune front of growth strategy. Here is centered on two key approaches androgen specific and parkway specific the antigen specific approach deploys immune and starts to modulate autoreactive T cells and diseases with a well characterized antigens such as type one diabetes and contrast, the pathway.
And specific approach is focused on induction and expansion of regulatory T cells for broad applications and numerous autoimmune diseases, but diverse antigens are unknown antigens as reported previously we've been collaborating with Merck on the outage and specific approach focused on two autoimmune diseases, one of which is type one diabetes and the other is undisclosed.
We've made significant progress on this collaboration which underscored the extension of our relationship with Merck late last year to focus on optimizing potential lead clinical candidate molecules. We recently presented a progress update on these efforts. We are talk on the Amgen specific tolerance meeting in January of this year those data slides by the way are available on our website. So please <unk>.
For you to review those today, however, we would like to focus on the significant progress with the pathway specific approach, where and we've generated a first in class fusion protein containing the two key obligatory signals of IL, two and TGF beta for generation of induced regulatory T cells or T. Rex. We believe this molecule also referred to.
Q4 O. One provides an unprecedented opportunity to reset the immune balance for numerous autoimmune diseases graft versus host disease and even transplant rejection. The next slide slide 20 provides additional insights into our focus on IP rates over the natural T regs or also known as <unk> and T regs and the <unk>.
Rex Constitutively expressed the high affinity IL two receptor alpha subunit and many current approaches have focused on generating IL. Two variants that are biased towards the IL. Two receptor Alpha also known as <unk> 25 to enable expansion of N T Regs and contrast, and as listed on the slide we believe that targeting the IP regs.
We are our approach provides a much broader opportunity and offer several advantages over and T. Rex. Most importantly from a disease perspective conversion of the pathogenic role repertoire of auto reactive T cells towards and regulatory phenotype is IP revenue is an attractive strategy for restoration of immune balance.
On the right side, you can see the design of Q4, and one which contains the two key signals for IP Rec differentiation and IL two variant and a TGF beta variant importantly, and in contrast to other approaches focused on and T. Rex. The IL two variant is not bias towards IL two receptor alpha and in fact this is the same IL two that is derived.
From the cue 100 series for oncology, which has been dosed successfully and human subjects and has substantive data related to the IL two moiety from a safety and Tolerability perspective to remind you Q1 on one our lead clinical candidate for in oncology from the 100 series has the same aisle to accept and Ohio Valency of four IL two molecules with.
And each molecule of one to one and then and on a different framework that targets tumor specific T cells in that context, and contrast, Q4 hundred one has a single molecule of IL two and the end terminals on the FC along with the TGF beta variant present on the system and as shown here for induction and expansion of induced regulatory T cells. The following slide 21 demonstrates pro.
And early data for Q4 O one dependent induction of T. Rex from <unk> positive T cells from healthy human donors and from patients suffering from inflammatory bowel diseases, IBD and rheumatoid arthritis already know that the level of T. Reg induction with Q4, and one is comparable to or better than what is seen with the recombinant and wild type IL two.
And TGF beta as shown on the open symbols here. Furthermore, as shown on the next slide slide 22, IP rates induced by Q4 to one demonstrate functional suppression of polyclonal effector T cells and these studies that were conducted with several human donors Q4 hundred one induced IP regs were incubated and varying ray.
<unk> was a responder effector T cells, showing SD responder here as you can see it wrecks induced by Q4 of one depicted by the Blue symbols Potently inhibits activation and polyclonal T cell proliferation stimulated with anti CD three CD 20 antibodies and contrast little to no suppression as noted with the low.
And do you have control of CD four T cells shown in Red based on what we've accomplished so far we remain highly committed to continue to develop this program forward towards the clinic. We believe Q4 to one could have the transformational potential for addressing the unmet medical needs for many autoimmune and inflammatory diseases.
Lastly, slide 23 connects the different pipeline vignettes and opportunities that are enabled by the cue 101 clinical experience the encouraging metrics with cue 101 with respect to safety and Tolerability favorable PK and exposure emerging PD and clinical data support multiple therapeutic opportunities as shown here first off it's I believe.
That that the immuno stat pipeline assets, including Q1, O two which targets wilms tumor one and the <unk> 12 Vale and molecules have a reduced risk profile due to the clinical observations of cue 101. Secondly, we also believe that the neo stat platform, which is a derivative of the IL. Two based 100 series and is designed to address tumor heterogeneity.
<unk> also directly benefits from the cue 101 clinical data third we also believe that the development of the bi specific ready stats as I. Just showed you designed to address tumor escape mechanisms of HLA loss on antigen presentation defects also derive benefit from cue 101 since the core IL two framework is essentially the same and lastly.
As discussed on novel Fusion protein Q4, 401 that induces regulatory T cells for autoimmune and inflammatory diseases contains a single molecule of the same IL two variant and incorporated into Q1 and one to summarize we believe that the depth and richness of our growing pipeline of programs and supported by the cue 101 clinical experience.
And we very much look forward to further developments as we move these various programs towards clinical testing with that I'll now pass the call along to Kelly to review the financial details and Gary. Thank you. Many turning now to slide 24, I'd like to provide a brief update on our financial results for the three months and year ended December 31, and 2020 the company reported calm.
Operations revenue of approximately <unk> 5 million and 1 million for the three months ended December 31, and 2020 and 2019, respectively. A decrease is primarily due to adjustments and the LG Chem and Merck collaboration and budgets and full time employee allocation.
And in the case of Mark the adjustments from Maitre, reflecting additional financial report that we will receive to further develop the preclinical product candidates under our research collaboration.
Search and development expenses were $8 million and 7 million for the three months ended December 31, and 2020 and 2019, respectively. This increase was due to the clinical trial activity for the Q1 on one monotherapy and combination clinical trials and hiring of research and development personnel and the first quarter of 2020 manufacturing.
Manufacturing costs for Q1 O two clinical material as well as development on the Neo stat, selling general and administrative expenses were $3 4 million and $3 1 million for three months ended December 31, and 2020 and 2019, respectively. The increase was due primarily to stock based compensation and legal fees incurred during the fourth quarter of 2020.
We reported collaboration revenue of approximately $3 2 million I'm, a collaboration with Merck and LG Chem for the year ended December 31, and 2020, a decrease of approximately 300000 from the same period and 29 cool. This decrease was primarily due to adjustments and the algae can and Marc collaboration budget.
Research and development expenses were $33 5 million for the year ended December 31, and 2020 as compared to $27 5 million for the same period and 2009 for this increase in R&D expenses is due primarily to an increase and the clinical trial activity for the monotherapy and combination trials on Q1 on one.
And our research and development personnel throughout the year to support our growing pipeline and.
Manufacturing costs for Q1 on one and he went on to clinical trial material as well as the development of any of that salt life.
General and administrative expenses were $14 7 million per the year ended December 31, and 2000 and 'twenty as compared to $12 7 million for the same period and 2019. This increase and G&A expenses is primarily due to increases and stock based compensation expense and legal fees, which were partially offset by a decrease and travel expense at the COVID-19 pandemic.
<unk> continued to hamper business travel throughout 2020, we finished the year with approximately $84 9 million and cash cash equivalence and marketable securities and working capital of approximately $71 2 million. During the year ended December 31, and 2020, we extended our cash runway with $56 7 million.
From the sale of our sales of common stock under our aftermarket equity offering true Stifel Nicholas and company, who acted as salaries and we believe our cash cash equivalence and marketable securities as of December 31st 2020, and will allow us to support the development of our immuno stat platform, including the quick and a little development of Q1 O one into the third quarter.
And if 2022 and I'll now turn the call back over to Dan for closing remarks, Dan.
Thanks Kerry.
As outlined on this call. Our primary objective is to develop novel drugs based on the.
And the immuno stat platform to provide meaningful therapeutic benefit.
For patients suffering from debilitating diseases by restoring immune balance.
Next slide Slide 25 depicts our growing pipeline of candidates through which we believe we are well positioned for creating substantial value and growth potential for our shareholders throughout 2021 and beyond.
And by continued execution of our corporate strategy, we aim to demonstrate our competitive advantages and market positioning of the immuno stat platform and associated programs. Specifically, we believe the cue 101 monotherapy trial provides a potential registration path forward as a single agent therapeutic and the.
Asian trial with Keytruda provides the prospects to enhance patient reach and market size by moving upstream to first line patients, where we anticipate the potential for significant mechanistic synergies as demonstrated in our preclinical studies.
We're continuing to develop a robust and growing pipeline of additional targets from the cue 100 series and its derivative programs Neo stat.
And the by specific ready staff as well as progressing our cue 300 series under our Merck partnership and defined indications with the auto antigens are well known and characterize Furthermore, as described by a niche. We have also recently developed a bi specific drug candidate and Q4 O. One indicated for autoimmune diseases with unknown.
And her multiple auto antigens, and we believe that through the ongoing development of cue 101, and our other cue 100 series immuno stats and our cue 300, and now 400 series, we have the potential to be positioned as a pioneer and breakthrough biopharmaceutical company that can transform immunotherapy through targeted immune modulation.
And of disease relevant immune cells directly and the patient's body.
Alright.
Moving on now to our expectations from milestones and achievements during 2021 as shown on the next slide 26, we anticipate continuing observations pertaining to Q1 on ones clinical activity and expect to select the monotherapy patient expansion dose and the monotherapy trial continued dose escalation.
Collation and our combination trial and commencing the neo adjuvant trial by the second half of this year.
Additionally, we anticipate filing of an IND for our second drug candidate Q1 O two and.
And the first half of 2022, we're also planning to initiate and expense CMC activities for cell line production of Neo stat, and K, Ras and <unk>, respectively, and the second half of the year and preparation for IND, enabling studies on.
Also we plan to achieve optimization towards completing proof of mechanism for the Q3 on one by year end, which would enable Merck to determined to proceed with further development for indications with the auto antigen is known and well characterized such as type one diabetes.
Furthermore, we plan to establish foundational preclinical data for Q4 hundred one for addressing autoimmune indications finally.
We'd like to thank our dedicated employees, whose commitment and professionalism throughout the challenges of the past year have allowed us to remain focused on execution of our ongoing corporate development.
We would also 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 promising therapeutic candidates for patients in need.
And most importantly, we want to thank the patients and their families involved and the clinical trials, allowing our clinical investigators to study and assess the potential therapeutic benefit of our promising drug candidates.
Thank you very much for your attention on todays call and your ongoing interest and I'd like to and I'll turn the call back over to the operator for questions.
Thank you and if he would like to ask a question. Please press star one on your telephone keypad and confirmation tone will indicate your line is and the kill.
Yeah.
You May press star two if he would like to remove your.
Hi, I'm from the cue and for participants using speaker equipment and may be necessary to pick up your handset before pressing the star. He's our first question is from Stephen Willey with Stifel. Please proceed.
Yeah, good afternoon, and thanks for taking the questions.
I Wonder if you could maybe speak a little bit to the kinetics of response that you're now characterizing and I understand that.
You kind of get this delayed.
Response, which is I guess somewhat characteristic of immunotherapy, but.
How does that interplay with some of the kinetics that youre seeing with respect to increases and antigen specific T cells, I think and that one patient to debt and the one big per cohort you had highlighted that they had seen a seven fold increase.
And he said and specific T cells, I think cycle five day one.
Are you seeing.
I guess kind of a graduated increase in.
And.
And those he said and specific T cells that kind of mimic what youre seeing in terms of lesion.
Lesion responses and then how do you think the interplay of this transient increase and T. Regs is contributing to these these response kinetics as well.
And I have.
Our niche answer the first part of that and Uh Huh.
Ken can elaborate further.
Clinical implications, yes, hi, Steve This is a niche so good question around T cells, we have noticed.
T cells as you pointed out and in and several subjects, including the patient.
Obviously, the biopsy sampling.
One of the things Steve that is <unk>.
Difficult to assess simply because of timing is to understand the kinetics of T cells in terms of evolution and that migration. So we have on sampling for this has been every 21 days there's obviously.
A lot happens between engagement and T cells are activated and extravasate to the tissue.
That's the part where we need to get a bit more insights and other words. The blood is a good surrogate for mechanistic biomarker, but ultimately what's happening and the tissue becomes very relevant and and maybe a vignette with well established provided by the pathology slide that can shed its essentially also the reasons Steve why.
And we've focused and really prioritized the neo adjuvant study that Ken has been driving and and along with Matteo now which is to have access to the tumor tissue to be able to make those frank assessments and our own.
The situation with the critical preclinical assessments, we saw enrollments disconnect between what we see and blood and tumor tissue was almost two orders of magnitude and some cases, where the richness was more evident and the tumor tissue and so that's an aspect we continue to remain focused on to better understand the evolution.
And the response and ultimately where it's homing too.
And in context of the drug design and the other thing I'd like to point us to even remind everybody is the key paper that was published by heat up Lou and our founder Steve valuable.
Late last year, and I believe and the October November timeframe and nature methods that made the point that the core scaffold with immuno stat and that case they use the peptide MSC part with immuno pet imaging to make the point that that could.
Penetrated extravasate and directly engage chosen the tumor lesion. So there is the potential for cue 101 to directly engage and rest of it and tis, which again any of that activity is not quantified by quantifiable by blood. So.
Much appreciate the limitations with debt, but having said that I think the emerging aspects of seeing this is particularly encouraging. These are late stage cancer patients as Ken pointed out with a compromised immune status. So we've got to take that into consideration and I think it would be interesting and history in the first line setting with Pembroke, which is a different call.
City of patients whether that signature seems different so.
So we are eager to understand that as for the T. Reg look these will Fox from three positive. These are transient and this is definitely not definitely but it likely points to the IL two pharmacology that to come back to baseline we have to track them out to sea.
Any evidence in sort of.
Downstream in terms of the tumor recognition reaction and I'll tell you from our preclinical studies in a with a murine surrogate of cue 101.
That was and any noticeably evident to us and those sorts of analysis. So again.
Keep an eye out on these things, obviously and try to understand but.
So far it seems to be trending with what we have set a noticed previously.
And Ken do you want to add on on the clinical side, Yes, I would just say I'd really quickly because you've.
Covered it.
And one of the questions that are out.
Folks have been worried about I think as are.
Are we delivering IL two to these patients because the drug has been so safe.
And these PD markers that the bump and T regs and the NK cells going up.
And the stimulate <unk> 67.
Stimuli.
Reflecting stimulation of the general <unk> population.
And then even more and the E. <unk> specific T cell population all reflect debt, we're delivering IL two.
And effective.
So I think that's what I read and when I see that T. Reg bump is you know IL two is going to stimulate cells T cells, all kinds of T cells and.
And that's what we're seeing along with the NK cells. So it.
Actually gives us a.
Comfort that we are delivering IL two.
Okay. That's helpful. And then just real quickly I know the intention here is to expand our cohorts four five and six I know that you have not yet reached the maximum tolerated dose.
So maybe you can just kind of speak a little bit to the decision to expand out cohort seven.
Yes, so and so I think all of the data that we're seeing suggests that we're seeing activity in that and that in the space of co one Meg too and.
Two and four Megs per King, we did not hit and MTV and cohort seven but we did see Smes that are suggested to us that if we don't need to go to that and I have a dose.
And we shouldn't we won't need to spell that out because I think we're going to find our active dose.
And the lower cohort doses, which will save.
And the amount of drug we need to use as well as potential toxicity is down the line.
We can always.
Used to expand later.
But we are really confident that we're going to see our debt.
Going to find our dose.
And somewhere between four and six.
Cohort.
Thanks for taking the questions.
Thanks, Steve Thanks, Steve.
Our next question is from Ren Benjamin with JMP Securities. Please proceed with your question.
Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress I guess, just dovetailing off couple of Steve's questions.
And when I look at the induce changes and be NK cells, and T regs and unless I'm reading it wrong.
On the NK cell seem to come.
Come back down a little bit by day, 15, and the T regs seem to be.
Maintaining a net and then coming down it doesn't look as transient.
So maybe just help me understand.
And what you guys are seeing here and whether or not it makes sense.
To start thinking about changing the dosing schedule.
As you evaluate these other cohorts.
And because maybe something a little bit more frequent could could help with the increase of debt. The NK cells of the CD eight specific cells and related to that any thoughts about combining this with.
Something like and if aluminum at.
Oh, I'm, sorry on <unk> four inhibitor.
Yeah, Ron I'll take the.
<unk>.
NK and T Rex and I just want to clarify on that graph that was shown on the NK is are in the black symbols. The T. Regs were in the red dotted lines and for most of the patients, which we've seen and what's actually quite nice here and evident, particularly as you see cohort five and six is a very nice expansion of.
And case that through 15, and sort of sustains theres a slight that's maintaining at an elevated level. If you see where the T Rex and the most of the subjects you know theres a transient uptick at about the day eight but by day 15, and all of them have trended down.
So we actually thought that as a positive differential between those two populations and as I mentioned, what Steve Austin when Youre asking.
And I'm sort of a related sense the.
And the effect and outcomes of this ultimately matters at the level of the tumor reaction and so as we start obtaining more biopsies as we start to understand mechanistically at the level of.
Even the neo adjuvant, setting and hopefully even try to get through that and our expansion phase I think it would be important to understand what is the representation of these populations.
Possible composition of the tumor infiltrates that ultimately becomes very important for us. So that is how we are thinking about of these observations and.
And so far as your second question for combination I think.
And as we think about the PD one checkpoint that of course Mechanistically makes very good sense to us. It's also backed by our preclinical data and <unk>.
There's data emerging from there that tells us.
That we.
And we should consider other checkpoints for mechanistic signatures, then and we've always sort of.
All of those opportunities and look at them with an open mind.
Got it Okay, and then maybe just as a second on the.
The neo stat, and the ready start platforms.
All look really exciting.
And especially the ready stat, I guess I'd love to get.
A little bit more clarity as to when do you see.
Those ultimately advancing to the clinic as it is it kind of full steam ahead for each of those programs and we think by 2022 or is this something that ultimately gets in the clinic a couple of years from now.
No rent and so we've been we've been working on ready status and the background for quite some time. We had these as I told you. There's really came about from these fundamental observations on looking at the literature emerging which we thought was really interesting different groups, making the same observations that a significant part of the tumor infiltrate and solid cancers, ovarian and colorectal lung and what the anti viral.
We'll protect our repertoire so we.
<unk> got a lot of data, which we haven't shown here, which we will be hopefully discussing and some future meetings. For example, we have data with that tool molecule, where we've made this with a tumor targeting on as an anti CD 19, and compared that to the sort of the anti <unk> three bite format and shown very comparable and kill.
And that's achieved at an optimal dose and at those doses, where you see optimal killing the target cell, which express a CD 19, we've not seen any non specific proliferation in that case, the virus epitope as a human and CMV epitope only activation of the CME T cells and we've not seen any production of inflammatory cytokines.
As with the tool molecule of the bite.
Non specific activation of T cells, and systemic cytokines, which is why.
I made the point that this could be a.
Really important way of looking at the immune reaction and harnessing what is a very robust repertoire that most of us on hardwood for decades.
And to repurpose that repertoire. So we are fully committed to when you say full steam ahead. That's how we're looking at this the choice right now is really looking at a variety of solid tumor.
And <unk> to make a choice of what day first candidate May look like but again coming back and linking this to cue 101, the core framework and so far as even the HLA component and the first iteration as they owe to the epitope as a virus epitope on the IL. Two is exactly the same IL two so we stand to gain a fair bit from those learnings, which hopefully.
As we sort of move this along the preclinical development should should aid and are in a significant manner.
Do you think that we could see this and the client by 2022.
I'd say and of 2022 late.
Early 2023, random and that would be a reasonable timeframe of course as you can imagine and.
In contrast, and Neo Stat, where we've initiated CMC activities is the cell line development for these call. It. These constructs that takes most of the time for the clinical grade material.
Great. Thanks for taking the questions and good luck. Thank you.
And <unk>.
Our next question is from Mark.
And Beth with Oppenheimer and company. Please proceed.
Yes, Hi, guys. This is Matt on for Mark and.
Thanks for taking on a question.
Maybe a couple of quick ones.
And in the ongoing study for cue 101 are you seeing any direct evidence of H L.
And the enrolled patients.
And for which we May see revenue stat is a better fit.
And as and immuno stat for these patients.
And do you anticipate presenting any preclinical data on this on this platform and upcoming medical conferences this year.
Yes, very good for the first point, we've actually not probed ourselves.
And these late stage patients what we do know is actually a very nice report that was published.
I believe from Foundation medicine, and a few months back.
That characterize loss of HLA across on and the head and neck cancer.
It's 30%, Ohio, I believe if I'm not mistake and so we know that there's a significant loss in particular and any of these late stage patients, which also which actually.
When you're doing the three by three if you just take that statistic one out of three patients may not have the substrate for which the immune system.
Dependent upon so we've not yet fully characterizing owned because you need obviously biopsies to be able to quantitate.
HLA expression and understand.
If it's in a little on sort of its component and loss.
We also low and the accompanying separate situation in the same disease, but and the cell therapy report published by Kite for example, they.
And they have noticed in broad HPV, driven cancers, not just head and neck that they see again about a third.
And of patients that have lost either the HLA or components with Amgen and processing and presentation again, bringing into focus that this is a very important tumor escape mechanism debt a lot of us.
And regardless of the platform on the approach may be susceptible to ultimately.
And so part of the preclinical data, we certainly are building of those packages and I would imagine and the second half of this year, we'll start releasing some of that data.
Okay, and then and then a follow up I guess I'm curious if it if it makes sense to us.
PDL one version of your ready stack.
Be applied universally.
Okay.
It's a very good idea and trust me. This is something that team internally continues and we've thought of this as well as even other modality scope within the tumor microenvironment. If you think about sopping up immunosuppressive.
Soluble modulators and cytokines and one of the strength. We have is the modularity of the platform allows us to do that which is to bring in a different module to be able to.
And look at poly specificity or falling pharmacology, if you want to call. It that so we certainly thought about it but there is an excellent idea. It's something we continue to internally vet and keep on the forefront.
Great. Thanks, Thanks for the question.
Great. Thank you.
Our next question is from Ted <unk> with Piper Sandler. Please proceed.
Great. Thanks, guys. Thanks have a thorough update and I can tell you <unk> been very busy with all of the work on the pipeline really exciting.
Also understand and appreciate.
The time, you spent laying out the differences with respect to analyzing patient. So looking forward to more data on that one of my questions were on.
I guess the ones that are primarily have is with us for one series really really cool concept here.
Because this is outside of oncology is this ultimately a program or an effort that you would envision partnering or is this an indication that.
On two may ultimately be moving beyond oncology with its own efforts. Thanks, so much for taking required from.
Yeah. Thanks Ted.
Obviously, an important strategic.
A decision for the company.
And it's one that we've.
And evaluating and and coordination with our board of directors because it has significant implications in terms of the trajectory of the company. We're principally focused on oncology presently in terms of our core competencies and capacity, albeit it's and immuno therapy centric organization.
Focused on protein engineering. The one thing we don't envisage is that we're going to be partnering.
Assets early on just true.
Partner them to divest so we intend to build a.
A dataset one from our observations and oncology.
Where the IL two moiety has already been in the clinic I think that bodes well for at least derisking. The the IL two side of the calculus, we didn't see immunogenicity on the.
The 100 framework. So what we wanted to do is make sure that we're building as much supportive data to enhance the value proposition and then look at let's say collaboration partnering Elias strategies that.
And maximize the value potential for shareholders I E, we're creating and enough of an impact with the dataset that we can retain upside potential and possibly even.
Some co development and the and the early <unk> going.
Yeah, and not like you need to make any decisions on that now but really highlight the.
Modularity and the platform so great update thank so much from the time guys I appreciate it thank you Chad.
Our next question is from Brian <unk> with Baird. Please proceed.
Hey, good afternoon, everyone. Thanks for thanks for taking my questions looking at the patient in cohort four.
And of course, that's on biopsy and kind of extrapolating that all book.
And cohort five which seems to have.
Tumor increase followed by my regression I mean, I mean for this patient cohort five do you guys think this is pseudo progression and that's that's occurring and the second patient and.
And now have you looked at any markers and structure the tumor out all that might be indicative of that I know I know circulating tumor DNA and sort of correlated with.
Pseudo progression and so and I think from data showing that you could delineate sort of progression on page Pat with a radio tracer update uptake I just wondering if you've looked into that at all or any of the other patients on a per share are sort of characteristics and pseudo progression.
Sure.
Appreciate the question Brian.
And when do you want to take that yes.
And it's a super question and as you probably know except for.
Melanoma, many immuno oncologist consider pseudo progression and quote unquote Dirty word.
And it's really hard to characterize characterize it what we do see.
And what we're seeing and.
And what Youre seeing and multiple clinical trials.
Around the world as well as and.
Everybody's clinics is that you do see these these then it takes a while for these lesions two to shrink.
And that as you follow these patients you do see some increases.
And in tumor size and.
And whether you call that pseudo progression or whether you call that tumor inflammation I think the <unk>.
<unk> certainly the debt.
And we had the biopsy on.
And you now have.
On a lesion that was a bit larger but also showed a.
This idea of necrosis as well as sarcoid like reaction showing inflammation lots of T cells suggests pseudo progression so.
We don't we like the rest of the Io field are evolving our thoughts about how to follow these people and that's one of the reasons why we're adding the I resist criteria to our exploratory endpoints.
The field is in general is not ready to replace resist with I resist resist is still the gold standard, but more and more investigators are using I resist to help guide their thinking.
And we don't have to.
And to be blunt, we don't have pet scan data.
And these patients.
And.
We've.
We are collecting circulating tumor DNA, but we are still going to be evaluating that as the trial progresses. So it's too early but it certainly has that flavor.
And then we're.
And we're seeing these and large lesions because of some inflammation.
And so I think I answered your question and you have.
To expound, if and you need more.
No that was perfect. Thank you.
And our final question is from C J and shoe with fair and Baird. Please proceed.
Hi, and good afternoon, Thanks for taking my question.
A few ones on cue 101.
So for Q1 on one.
I think it's your first time, showing the NK cells and expansion data very very encouraging I guess, how do you think how do you could this this this data.
With the T cell on expense.
And on expansion data specific to only <unk> specific T cells.
And get expense I guess.
Hi.
I guess what type of.
Sales do you think if they really do the heavy lifting anti tumor activity.
Yes look those are the two very the two related but two very distinct because the NK effects of IL two R and lineage effect as you can imagine so you see this movement across patients, which is great and as Ken mentioned, it's one of the most clear metrics of inactive IL two compound so we ask.
We are delighted to see that it's also good to have a component of.
Poly activity with different cell types that hold and tumor potential.
On the T cell side, we've noticed this in the periphery. We've reported examples and early evidence of <unk> seven expansions of course, Thats, a railroad frequency, particularly as youre talking about even late stage patients, but even in the healthy as you well know the antigen specific repertoire to characterize on.
Dominant specificity.
It's not at the same degree as when you have and lineage specific effect ultimately at the level of the tumor reaction I think if you look at mechanistically that both have and opportunity and they both could be active.
From some of the biopsy and again. This is early days that Ken presented you could clearly see that <unk> that would juxtaposed next to cancer cells that expressing that were also expressing PD ligand, which Furthermore, sort of also validates and supports the mechanistic combination with PD one, but this has to be obviously and looked at now and a more deeper.
As we continue to hopefully access tissues, and again keep on coming back to the neo adjuvant and not to belabor the point, but that provides us with the with.
With clear access and.
In terms of making those comparison and ultimately as this of this sort of ties together and and patients derive benefit hopefully, even though the level of survival benefit.
Its become apparent on the longer term as these follow ups happen. So we think again not to exclude we've kept our eyes very wide open but it's good to see a and the fact that we started to notice at the level of tumor specific T cells. It's good to see this now with NK cells.
We know by preclinical data that we've presented and say with the WT one compound and this is with all ex vivo human T cells.
That our expanded with Q1 or two for example, which is a derivative of the same framework and say it was noticed with 101 that these T cells are polyfunctional they produce pro inflammatory cytokines. They are brands I'm positive.
Target cells.
So I think it will have a lot here, we'll learn a lot as we sort of continue to gather these data, but the early metrics are certainly supportive to Cds Cds.
These impacts on what on what we believe are obviously very relevant populations for and anti tumor T cell response or on anti tumor immunity.
Got it and then for the for the first line combination treatment I think that and that was probably the most interesting.
Potential debt, how do you think about.
Going through and registration trial, and what kind of data and you're looking at in this and this.
And this data readout and the second half.
Sure Let me Ken Let me just take that generically then I'll turn it over to you sure. It's an important question and look we made a very deliberate decision to go into this with second line and beyond as a single agent to clearly demonstrate the mechanistic underpinnings of 101 and the.
The 100 series. So we're actually really impressed and pleased with the data would generate and to date both from the standpoint of the.
And the Tolerability, but the fact that we are seeing T cell increases NK cell increases, we're seeing and anti tumor effect is.
Evidenced on on scans were seeing some tumor shrinkage tumor stabilization, but most importantly, that's translating qualitatively and to data as we look downstream, where we are seeing evidence of tumor necrosis ultimately what matters is the survival of those patients. So we still are very confident.
And bullish on the prospects of monotherapy with these patients let's not forget these are very compromised.
And poor state patients don't have a standard of care. So we're still optimistic and positive about the monotherapy prospects for a registration path and.
And then the combination.
And the rationale there is mechanistically, we're expecting to see some synergistic effects because of the fact that <unk>.
<unk>, our other checkpoint blockade approaches and essence require and endogenous population of activated T cells to have therapeutic effect and thats, what our platform is in essence.
Driving to achieve which is increasing that debt endogenous T cell repertoire. So we think it bodes well for both the monotherapy and the combination and Ken I'll turn it to you to elaborate.
Yes, I would.
Just say you know when you think about the combination and you think about Pembroke being approved and that first line setting.
Youre talking about response rates around 18% overall as well as.
You know a survival benefit of a couple of months compared to <unk>.
To chemotherapy.
So we recognize that.
If you look at our data from the mouse models that the combination.
Q1 on one plus and anti PDL, one antibody was much better.
There was more clearly synergistic activity. So we believe that there is a combination study will lead to a registration.
Path, because we believe we will.
The two drugs together, we will have a much better <unk> and a much better overall survival.
Advantage and then <unk>.
<unk> alone.
Got it and.
And final question on.
Q4 O one.
Since you are using the same same Iot ovarian as Q1 O. One I guess, how do you think about the potential dosing here and what would you use even lower dose IL two for forgiveness.
On <unk>.
I T regs and rationale.
Yes, I think look from a from a biology, it's obviously very different and it's very different than low dose IL two proleukin debt has been tested and <unk>.
Growth versus host disease, and human subjects or in patients with autoimmune diseases, including us.
IBD and vasculitis. These papers route there and but and Thats and that is different from the high dose IL, two and thats used for conventional cancer immunotherapy I think the fundamental difference here Z is the fact that it's just not the IL two but also a TGF beta component, that's delivering and active signal so wild.
And we take obviously a lot of comfort and confidence from the established safety and Tolerability of.
101, we actually don't anticipate going to these sorts of levels.
And just started early investigations into in vivo model systems to better understand that relationship and again that pharmacology is slightly different than what has been done and the field or what is it still being done and the fee, leaving with the IL two variants, where the biology is a singular acts as a vital tool that is no.
The play here the play here is actually differentiating and two of lineage phenotype for the CD four taking advantage of two key signals on IL, two and TGF beta so we've got a and b.
Obviously, you got to understand this and a different manner than what it has been conventionally done, but we know from some of the early data that is emerging that this is a very sensitive.
So it that can be triggered effectively and that gives us confidence that we will have an enormous safety window compared to where what we've already learned with 101.
Got it got it.
Thank you very much.
Thanks, <unk> and thank you.
And <unk>.
Ladies and gentlemen at this time and I'm showing no further questions I would like to ask the question and answer session and turn the conference back over to management for any closing remarks.
Alright, Thank you and thanks, everyone on today's call and for those that will be listening in on our archival recording.
And for your ongoing interest and cue Biopharma and we look forward to providing updates on a continual basis as we continue to make progress during the upcoming quarter. So thank you very much and everyone take care of yourselves.
Thank you. This does conclude today's conference you may disconnect. Your lines at this time and thank you for your participation.
Thank you.
And.