Q2 2021 Cue Biopharma Inc Earnings Call
[music].
Greetings and welcome to the cue Biopharma second quarter 2021 earnings call. At this time all participants are in a listen only mode. A brief 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.
As a reminder, this conference is being recorded it is now my pleasure to introduce your host Dr. George The Voytko. Thank you George you may begin.
Thanks, Paul and good afternoon, everyone. Thank you for joining us on today's call are Dan for Surrey, cue Biopharma CEO, Dr. Anish, Suri, President and Chief Scientific Officer, Dr. Ken Pienta acting Chief Medical Officer, Dr. Matteo <unk> Senior Vice President of clinical development, and Terry Bill and MLR.
Chief Financial Officer.
Before I begin I would.
I'd 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 purposes of the private Securities Litigation Reform Act of 1095 actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those.
Discussed in the risk factors section of the company's annual report on Form 10-K filed with the SEC on March nine 2021, as well as other filings made by the company with the SEC from time to time, which can be accessed on the Edgar database at Www Dot SEC Dot Gov.
In addition, any forward looking statements.
<unk> represents the company's views only as of today August 17th 2021, 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 to change please.
Please be advised that today's call's being recorded live and archived versions of the event can be accessed via the company's website for the next 30 days.
That I would now like to turn the call over to Dan for Surrey here.
<unk> Biopharma CEO, Dan Yeah, Thanks, George and good afternoon, everyone and thank you for joining us today for a review of our ongoing progress as well as second quarter 2021 financial results, which are available in more detail in our Form 10-Q filed with the SEC on August nine.
Our agenda for today's call is shown on the next slide slide three.
I'll provide a brief overview of ongoing progress since our last earnings call highlighting recent developments with an emphasis upon.
Our lead clinical program Q1, O one and strategic implications for the cue 100 series regarding our competitive positioning and potential value creation for our shareholders.
After the introductory update I'll turn the call over to Dr. <unk>, <unk>, our president and Chief Scientific Officer.
Who will provide a synopsis of our approach for selective targeting of IL. Two after a niche provides an overview with background context, Dr. Ken Pienta Iraqi CMO and Dr. <unk> <unk>, our senior Vice President of clinical development will provide an overview of our ongoing cue 101 clinical trial.
First in representative program from the IL two based cue 100 series.
Kevin Matteo will then turn the call back over to a niche who will provide further details on the expansion of our pipeline with the premise that cue 100 one's development progress.
Essentially derisked and enhance the value proposition of subsequent programs due to the platform's modularity.
Gary Miller, our Chief Financial Officer will then provide a summary of our financial results for the past quarter and I'll close with a summary prior to opening up the call for questions Alright.
Alright to begin I'd like to remind you of our foundational goal and that's stated here on slide number four.
Which in essence is to design develop and bring to patients in need rationally engineered biologics with the aim of restoring immune balanced by harnessing natures own queues.
Since our name.
Our selective and specific modulation of disease relevant T cells directly in the patient's body.
So we believe we're well under way to realizing our vision.
Leading the next wave of disruptive breakthrough immuno therapies addressing the specificity and diversity of the human immune system to cure complex human disease.
I'd first like to begin with Q1 O. One our lead development program, which is representative of the IL two based cue 100 series.
On the previous earnings calls, we reported results pertaining to a refractory heavily pre treated patient that had a confirmed partial response or PR from the monotherapy phase one dose escalation part of the Q1 O one trial.
This patient remains on study and as kind of Matteo will discuss momentarily has demonstrated a durable PR after multiple scans with our latest scan evidence seen additional tumor reduction.
We view this durable and ongoing resist confirmed partial response as an important derisking event confirming the ability of cue 101 to selectively engage and continually modulate T cells and a challenging patient population.
While still early in development, we believe that the growing body of clinical data is encouraging and supports the promise and potential of Q1 O. One having a registrational path forward as a monotherapy in third line and beyond HPV positive head and neck squamous cell carcinoma patients.
Furthermore, as a niche will discuss we also view the data as supporting the premise that our IL two based cue 100 series represents a potential breakthrough development and the clinical application of IL two for cancer immunotherapy per se.
As the drug candidates candidates mechanism of action is based upon activating cancer specific T cells directly in the patient's body.
In the case of Q1 O one that HPV <unk> specific T cells. We believe this growing body of data supports our position that not only could cue 101 have a possible registration path as a single agent.
But may also enhance patient reach and therapeutic benefit.
<unk> HPV positive head and neck cancer patients in combination with <unk>, which is currently the standard of care for these patients. The combination trial referred to as keynote <unk> 878 is presently enrolling patients in the second dose cohort is kind of Matteo.
<unk> really discussed during the clinical update section.
So in summary, we believe the ongoing data emerging from the monotherapy trial to be transformative for cue biopharma as it provides a preliminary objective evidence of clinical activity as a single agent monotherapy in a late stage prior treatment refractory patient population.
And clearly differentiates our drug candidate Q1 O one as well as our IL two based cue 100 series from competing IL two modalities in vaccine programs as.
As we continue to observe supportive data in our ongoing phase one dose escalation and expansion trial.
It's important to recognize that these data could not only provide potential risk reduction and validation for cue 101, but also by implication the entire IL two based cue 100 series the.
The underlying framework for the IL two based cue 100 series remains essentially the same across programs with the only primary difference for example between Q1 O. One in Q1 O two being the nine to 10 amino acid antigenic epitope in the MHC, our HLA binding growth.
The key features underlying our ability to target selected cancer relevant T cells is based upon engineering a molecule that built upon fundamental principles of T cell activation.
Our niche will now elaborate upon these characteristics and features of the cue 100 series and the foundational importance of these observations as it relate to the selective delivery of IL two to tumor specific T cells are niche.
Thanks, Dan and good afternoon, everyone I'd like to begin by highlighting the objective of the immuno oncology sector to activate a cancer specific immune response, while avoiding the unwanted deleterious effects due to nonspecific immune activation.
That and we believe that our cue 100 series immuno stat platform enables the selective targeting of interleukin two or IL two to tumor specific T cells.
As shown here and evidenced by the number of pharmaceutical and biotech companies developing IL two centric approaches.
IL two is a well validated target for cancer immunotherapy, albeit with associated liabilities and limitations I have two.
As an approved biologic therapy for metastatic melanoma and renal cell carcinoma. However, the lack of selectivity and safety have hindered its broad application and wider clinical potential examples of associated toxicities include vascular leak syndrome, and cytokine release syndrome, along with Undesigned effect on many immune cells.
During the activation of regulatory T cells, which may contract anti tumor immune responses.
As such a significant opportunity exists for next generation IL two approaches to address and circumvent these challenges through rational protein engineering, we appear to have met this challenge and have the prospect of a breakthrough solution, enabling the true potential of IL two for selective immune activation the next.
Slide six highlights the challenges with lack of cellular specificity of IL, two or IL two variance.
Shown here only a minuscule fraction of the entire CDA T cell repertoire harbour specificity for tumor antigens note that the tumor specific T cells here are shaded in red while the non tumor specific T cells shaded yellow.
Last majority of our patients T cells likely greater than 99, 9% directed against other non tumor specificities in this context, a wild type IL two or a variant of the IL two molecule like a non alpha IL two will be inclined to indiscriminately engage the vast majority of <unk>.
T cells with little relevance to the mine of tumor specific T cell fraction. The result of these nonselective interactions is appraise and activation of the broader immune compartments with no selective bias towards the tumor specific T cells. This lack of specificity coupled with safety considerations creates significant barriers for extract.
The fullest potential.
Of IL two treatment.
We sought to find a protein engineering solution to this challenge as shown in the next slide slide seven the breakthrough here was that we exploited our immuno stat platform to specifically select for Niall to variant in context of tumor specific T cell activation. This is very different from what others have done.
Or are we believe are doing which is to select foreign IL two variant only in context of interactions with the IL two receptor subunits, we know from fundamental immunological principles that a key step in T cell activation is engagement of the T cell receptor or TCR to specific peptide HLA complex molecules.
Hence we use this natural biological mode of T cell engagement to design. The cue 100 series of immuno stats, which contained tumor peptide HLA molecules along with modified IL two as shown in the left panel of this slide the modified IL. Two is designed to selectively act upon tumor specific T cells, whose TCR.
He is engaged to the BHL a component of the cue 100 series immuno stat. If the TCR is not engage as would be the case with the vast majority of the non tumor specific T cells shown in yellow.
Then the signal from the IL two variant on its own is relatively weak hence the cue 100 series is a molecular scaffold that exploits both TCR and IL two signals to set the optimal signal amplitude for selective activation of tumor specific T cells. The ribbon structure in the right panel of this.
Slide provides molecular details of the configuration of the IL two based cue 100 series. Each molecule is built upon an antibody FC scaffold and consists of bi valent peptide HLA molecules shown in blue that engage tumor specific T cells, along with two molecules of IL two on either side for a total of four IL two molecules.
The IL two variants has two key changes one abrogates binding to the IL two receptor alpha which helps mitigate safety issues with systemic activation and minimize the bias towards regulatory T cells. The second mutation reduces binding to the IL two receptor beta subunit such that the composite signal strength for T cell.
<unk> is dependent upon additional signals from the Tcs engaged to the PHA component. This tuning of signal amplitude insurers buys the activity of IL two with TCR engage T cells. The next slide slide eight highlights the preferential activity of the cue 100 series immuno stats on tumor specific T cell.
Over the majority of T cells that are not specific for the tumor.
There are several advantages to our approach one as mentioned the selective activity of IL two on TCR engage T cells, both insist and trance interactions.
Since interactions since interactions would be tumor specific T cells that engage the peptide HLA and IL two components of the immuno stat trans interactions refer to the IL two variants activity on other tumor specific T cells, whose tcs, maybe engage with either <unk> or antigen presenting cells in the tumor or lymph nodes.
We believe this potential could further expand the antigenic diversity of the anti tumor T cell response.
Furthermore, we've demonstrated expansion of NK cells, which could be an added benefit for cancer immunotherapy, while the effects on T regs or regulatory T cells have been transient.
Taylor will discuss these findings in the clinical section of this.
This presentation lastly, we have observed a generally favorable safety and tolerability profile.
Lead candidate cue 101 has been dosed up to eight mixed but kick in patients with no M. T D.
Next slide slide nine further exemplifies the differences between wild type IL, two or IL, two variants and a 100 cue 100 series.
For the wild type IL, two or this variance the lack of IL, two selectivity and associated safety issues limit the clinical dose that can be administered to the patient for example, the approved clinical dose for the wild type IL two aldis, Luke and his 37 micrograms per kilogram with a half life of about 80% to 85 minutes.
Similarly for the various not alpha IL two variants the chosen clinical doses that range between 6% to 24 micrograms per kilo Grandma's shown here. In contrast, we have successfully dosed cue 101, our lead clinical candidate from the cue 100 series up to eight milligrams per kilogram with no MTB having been identified.
Hence, we believe that Q1 O one demonstrates a dosing range for IL two with inadequate therapeutic window. This will be discussed further by Ken and material in the followings.
Sections focused on the clinical data, okay with that I'd like to hand, the call over to Ken Ken.
Ken.
Thanks, <unk> and good afternoon, everyone as shown here on slide 10-Q, one O. One shares the core scaffold of the cue 100 series. It consists of a peptide from the east seven protein of HPV 16, or human papilloma virus, coupled to the HLA E O two molecules along with the IL two variants.
I buy any.
One is designed to selectively activate HPV seven.
Sales to target cancers, driven by the human papilloma viruses, such as head and neck cancer and others.
Molecular design of Q1 O. One enables us to identify eligible patients based on HLA, <unk> positivity and HPV 16 positivity for the tumor.
As always I'd like to thank our principal investigators and the patients participating in our ongoing clinical trials as we've noted on previous earnings calls we have continued to successfully screened and their own role HPV 16 positive head and neck cancer patients to participate in our Q1 on one clinical trial.
Throughout the COVID-19 pandemic.
Furthermore, despite the challenges of the Covid pandemic to date, we have successfully executed on our defined development plans and timelines.
And to have achieved our stated objectives on schedule.
Next slide Slide 11 shows our high level summary of the clinical design and dosing cohorts for our ongoing phase one trial of cue 101, enrolling third line and beyond patients that are HLA, <unk> positive with recurrent or metastatic head and neck squamous cell carcinoma driven.
By HPV 16, we completed enrollment in the part a dose escalation portion of this trial and are now enrolling into the part b dose expansion phase of the trial at the presumed a recommended phase two dose of four mix per gig representing the dose cohort six of the part a dose.
Escalation, our expectation and projection is that we will complete enrollment of 20 patients by early first quarter 2022.
The next slide Slide 12 provides a high level summary of the observations made over the course of the dose escalation part of the study.
<unk> 38 patients were treated across seven dose escalation cohorts without an MTBE being identified one confirmed we are in eight patients with confirmed stable disease lasting for more than 12 weeks have been observed pharmacodynamic markers of therapeutic activity include the.
Demonstration of expansion of his relevant CDA positive T cells, and NK cells and evidence of tumor invasion by tumor infiltrating T cells or T cells, we will be providing an update data at <unk> as well as towards the end of the year on these trials I will now pass the presentation to.
<unk> to discuss some of our current data Matteo.
Thanks, Ken.
The next slide Slide 13 shows some of the details about our enrolled patients to date.
The majority of our patients more than 90% have been treated with cue 101, as third line or beyond therapy. After failing both platinum based chemotherapy and checkpoint inhibitor.
Many patients also failed treatment with the epidermal growth factor inhibitors. It tucks in math. This is an important note. Although our R&D was originally cleared by the FDA to test Q1 O. One.
Second line agent after platinum failure.
First line Pampa Legit Mab was approved in the first and second line settings as our trial was being initiated.
Externally. This is de facto shifted this trial into the third line setting and beyond.
There is no approved therapy for recurrent HPV positive head and neck cancers.
While presenting the increased challenge of treating highly pretreated in refractory patients. We believe that this opens a potential registration path for Q1 O one SEC.
Several ongoing observations give us confidence that our data is maturing in a manner that could allow us to define multiple potential registration strategies with the FDA first as shown in slide 14, our data to date demonstrate the tolerability of Q1 O. One in patients both as a monotherapy.
And in combination with Pembina Lizzie map are presumed recommended phase two dose for migs per kg appears to be well tolerated in the target population, our first cohort of patients in the combination study.
Q1 O one dose did one Meg per kg did not experience a D. L. T and we are now enrolling the second cohort at two Meg per kg Q1 O. One in combination with Pember Elysium bad.
All of the Esa He's an AE is observed to date are consistent with those observed with IL two administration.
Or are typical of those observed with checkpoint inhibitors in the treatment of cancer patients. The most common aes observed continued to be fatigue, and anemia and decreased lymphocyte counts.
Second our pharmacokinetic data at the recommended phase two dose as shown in the next slide Slide 15 reveals consistent exposure without any evidence or effective anti drug antibodies on PK and exposure in patients that have received multiple doses of Q1 O. One as shown in the bottom panel.
Of this slide.
Third PD data as shown in slide 16 demonstrates the consistent increase in natural killer cells or NK cells across all subjects in cohort six in contrast, we see a modest and transient increase in CD four positive Fox P. Three positive T cells consumer.
<unk> regulatory T cells or T regs.
Returns to baseline levels. Shortly after dosing. We have also reported on evidence of increase in tumor specific T cells, and example of which will be shown later.
Importantly, we have observed what appears to be a dose proportional PD effect as well as corresponding clinical benefit.
Eight patients with stable disease lasting greater than 12 weeks a confirmed PR with the majority of these observations occurring in cohorts five and six I E. A doses of two and four migs per kg respectively.
The data generated in the dose escalation part a of the trial demonstrated signs of clinical activity from observations and scans from cohorts four and five and six that demonstrate durable stable disease. Furthermore of the dose escalation demonstrated what appears to be a relatively broad therapeutic window with the dose range between one and four.
<unk> per kg, where PD activity as well as clinical activity and benefit had been observed while appearing to be well tolerated. We also observed and continued to exert clinical benefit within the higher dose cohorts and I've had two additional patients recently demonstrate confirmed stable disease on their early scans we remain encouraged.
By this growing body of data and it's been as conveyed by can believe we have a potential registration path.
Going forward, including as monotherapy for third line and beyond as an update from what was reported in the previous earning calls.
Turning to slide 17, with histopathology evidence and clear signs of antitumor activity of T cell infiltration. This patient has been reported by the P. I as evidenced seeing no signs of active cancer up to six months post resection.
The next slide Slide 18 also shown during our prior earnings call demonstrates supporting data for the mechanism of action of Q1 O. One we clearly observed a significant increase in tumor infiltrating lymphocytes within the tumor tissue post treatment with Q1 O one demonstrating grand design B.
Serine protease found in the granules of NK cells, and cytotoxic T cells. It as a weapon utilized by these cells to kill target cancer cells. This slide demonstrates biopsies from a patient in cohort five before and after administration of two doses of Q1 O. One in the post treatment picture on the right and quantify it on the graph.
On the far right you can see a marked increase in cytotoxic T cells secreting granted b again, providing valuable validating data supporting the mechanism of action of Q1 O. One.
Hence mechanistically the immuno stats have the potential to directly engage tumor infiltrating T cells and NK cells, which may also altered the local tumor microenvironment to favor anti tumor.
Immunity.
This mechanism of action of Q1 O. One will be further explored in an investigator sponsored new adjuvant trial at Wash U Washington University in St. Louis in which treatment naive patients will be given Q1 O. One prior to a surgical resection and their resected tumor will be examined for evidence of tumor infiltrating lymphocytes.
Fourth the clinical benefit rate as a single agent during the escalation phase of the protocol is encouraging slide 19 demonstrates a partial response in a patient treated at the recommended phase two dose now out over 28 weeks on therapy.
Increases in HBV E seven specific CDA T cells and NK cells were observed in this patient as well.
Slide 20 shows a reduction of approximately 57% in one of the patients target lesions.
We all recognize that Prs and Crs occur infrequently in third line and beyond HPV positive head and neck squamous cell carcinoma patients. Importantly, we are also following patients for clinical benefit which is defined as patients with at least stable disease on study for more than 12 week.
In the dose escalation phase of our study to date, we've observed a preliminary clinical benefit rate of approximately 27% in the third line and beyond patients as noted in previous earnings calls. We also continue to monitor progression free survival and overall survival closely and continue to observe what appear.
There has to be an enhancement of survival of patients in the Q1 O. One dose escalation trial with all the caveats of a relatively small number of patients were intrigued and encouraged that the first 90 patients on this study treated with the lowest doses of Q1 O. One had a median overall survival.
Greater than 12 months, we continue to follow patients sooner or later cohorts and of course this will be an important metric to follow and a recommended phase two dose cohort as we finished accrual and monitor these patients.
Our clinical trial protocol amendment for the expansion phase now cleared by the FDA since the last earnings call.
Allows.
For patients to remain on study at investigation.
Seagate or discretion, if they demonstrate radiographic progression, but are clinically stable.
Furthermore, as measuring response by I resist to the exploratory endpoints and also allows the collection of data regarding follow on anticancer treatments patients may receive to gain further insights into our survival observations.
I will now hand, the call over to Ken to summarize our registration strategy.
Thanks have a Tam we believe that these exciting clinical observations and the observed supportive our pis, who continue to accrue patients to this study provide supporting evidence that cue 101 is an active agent with promising potential for HPV positive head and neck squamous cell carcinoma patients.
And our emerging data opened several potential options for a registration path.
First we will be able to perform a registration study as a third line therapy for HPV positive head and neck cancer as shown in slide 21. There may also exists in option for second line therapy in Cps.
Score patients less than one who are not eligible for pepper loser map.
Second also showed in slide 21, we will continue to perform a study in first line HPV positive head and neck cancer in combination with kimbrough as a potential registration path third we will be initiating our neo adjuvant study.
Washington University in St. Louis with the intention to demonstrate the value of two <unk> hundred one treatment in patients prior to primary treatment.
Fourth we plan to initiate an adjuvant study at Johns Hopkins in 2022 with a goal of demonstrating the value of Q1 O. One with Pam grow in patients at high risk of recurrence at this juncture I turn the call back over to a niche for a brief synopsis regarding the expansion of our.
Our drug candidate pipeline based upon the cue 100 series framework finish.
Thanks, Ken as conveyed throughout this call the data emerging from our ongoing monotherapy trial of cue 101 supports the design of the IL two based cue 100 series, which can selectively modulate tumor relevant immune cells to enhance therapeutic benefit and circumvent oil to talk.
<unk> a key strength of the immuno stat platform is its versatility and modularity with respect to swap in different tumor derived T cell epitopes to change the indication of interest as an example, Q1 O one targets HBV E. Seven specific T cells, while Q1 O. Two on next clinical candidate targets.
Wilms tumor one or WT, one specific T cells are.
As shown in the next slide Slide 22, WT, one has been widely recognized as an attractive tumor antigen and is up regulated in numerous solid tumors and hematological cancers, including colorectal pancreatic and AML amongst many others most of the molecular framework, including the IL two molecules are identical between Q1.
Oh, one in Q1 or two with the primary difference being the 9% to 10 amino acid T cell epitope that as tumor specific.
Next slide slide 23 highlights the preclinical data for Q1 O tools ability to prime and expand WT, one specific T cells from human blood ex vivo and in vivo in transgenic mice treated with Q1 O. Two also shown in the bottom panels of the slide are the data demonstrating poorly functionality of <unk>.
One specific T cells that are activated by Q1 O two and their ability to kill WT, one expressing target cells, both in vitro and in vivo as shown on the next slide Slide 24. It is our belief that our immuno stat pipeline assets, including Q1 O. Two in Q1 O three which targets a mutated <unk>.
It will be T cell epitope have a significantly reduced risk profile and enhanced value potential due to the clinical observations of Q1 O. One we have been deliberate regarding a development strategy, where in Q1 O. One establishes a beachhead or a foothold upon which we intend to expand drug candidate pipeline.
And our market potential we believe this strategic vision allows us to harness the maximal potential of IL two in cancer immunotherapy.
I will now hand, the call over to Carey to discuss second quarter financial results and will then return for brief closing remarks, Kevin.
Thanks, Anish, turning now to slide 25, I'd like to provide a brief update on our financial results for the three months ended June 32021. The company reported collaboration revenue of approximately $2.7 million and $1.1 million for the three months ended June 32021, and 2020, respectively.
The increase of $1.6 million was primarily due to additional research and development and contract manufacturing activities and preparation of an investigational new drug filing of our Q1 O. Two our second drug product candidate from the Iot based cue 100 series, which is planned for the first quarter of 2022.
Search and development expenses were $8.8 million and $8.1 million for the three months ended June 32021, and 2020, respectively. The increase was primarily due to an increase in laboratory and drug substance manufacturing costs as well as clinical expenses general and administrative expenses were $4.3 million and $3.9 million for the treatment.
Ended June 32021, and 2020, respectively.
The increase was due primarily to stock based compensation and legal fees incurred during the second quarter of 2021 as compared to the same period in 2020.
We ended the quarter with approximately $73.9 million in cash and cash equivalents and working capital of approximately $63 million, we believe our cash and cash equivalents as of June 32021 will allow us to support the development of our immuno stat platform, including the clinical development of Q1 O one well into the fourth quarter of 2022 now.
On the call back over to Dan for closing remarks.
Thanks, Gary.
In conclusion, the observation of clinical activity of cue 101, as a monotherapy in this challenging and heavily pretreated patient population.
Is in fact, an important step forward and supports the potential of not only our Q1 O. One drug product candidates, but also for our follow on drug product candidates as well such as Q1 to Q1 O three.
From the IL two based 100 series, providing valuable proof of concept of the immuno stat platform to activate and expand cancer specific T cells and NK cells directly in the patient's body as a method to treat a myriad of cancers. We believe the data continuing to emerge from our ongoing cue 101.
<unk> trial supports the premise that our approach has in essence created the next generation solution to utilizing IL two is a targeted and selective immune activator for treating cancer.
Furthermore, we believe the data demonstrates clear competitive advantage over other modalities and provides <unk> biopharma and its shareholders with a strong foothold upon which to further demonstrate expand and establish this competitive positioning.
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 have successfully executed our stated corporate objectives throughout the year and believe the cue 101 monotherapy trial provides a potential registration path forward as a single agent therapeutic and the combination trial with Keytruda and provides the prospects to enhance patient reach and.
And market size by moving upstream to frontline patients, where we anticipate the.
The potential for significant mechanistic synergies as demonstrated in our preclinical studies, we look forward to providing trial status updates on a going forward basis.
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, even through the past year with the train.
Times with Covid.
I would 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.
We think our principal investigators and staff at our clinical sites will remain excited about Q1 O wanted in our rolling patients in our studies.
Most importantly, we want to thank the patients themselves and their families involved in the clinical trials, the courage and willingness to be part of a clinical study allows us the opportunity to assess potential drug activity and assess the potential for therapeutic benefit of a promising drug candidates.
Thank you very much for your attention and interest and I'd like to now turn the call back to the operator for questions operator.
Thank you, we'll now be conducting a question and answer session.
We'd like to ask a question. Please press star one on your telephone keypad, a confirmation tone will indicate that your line is in the question queue. You May Press Star two if you would like to remove your question from the queue for participants using speaker equipment. It may be necessary to pick up your handset before pressing the star keys.
One moment, please while we poll for questions.
Thank you. Our first question comes from Mark Breidenbach with Oppenheimer. Please proceed with your question.
Hey, good afternoon, guys and congrats on the progress.
Just a few few questions from me first with respect to the selection of your dose to take forward into the expansion cohort or cohort I think Ken mentioned that you saw dose dependent PD markers maxing out around the port Mig per <unk> dose and that help you.
Okay.
I'm just wondering does that imply there was sort of a bell shaped.
Dynamic response and did it actually got a little bit worse.
For King and if so.
Speculation as to why you have to be the case.
Yes, Mark I'm going to let our niche take that question, but I just want to clarify I mean, we went up to seven cohort, which was at eight mix for King we didn't actually see a plateauing on PD et cetera. It was the emergence of off target <unk>.
Activities that we felt since we had a therapeutic window emerging between one meg per kg and for mix per kg.
We were better served to.
With the cohort six dose, which was just much better tolerated. So I think that was the key metric. It wasn't that we saw the PD plateauing, but I'll turn it to a niche to elaborate yes, I think thats right, Mark where we saw the BD signals clearly emerges around the cohort.
Four dose, which has been subsequently continued to build on through five and six.
And have not we've not seen a bell curve, but we certainly when you look at the for example, broad changes in N case, which is a broad.
Too sensitive population that tends to be very consistent that these high doses and that we thought was very favorable for the choice of the RP to do similarly as material.
Mentioned in contrast, when you see the other end of a very oil too sensitive broad population vis vis the regulatory T cells T. Regs, we saw that transient uptick, but then return back to baseline and then we sort of made sense to us that they seem to be a really great window to be in.
Okay.
And can you just remind us on the study if the patients were receiving prophylactic oral or IV fluids to prevent hypertension associated with vascular leak doesn't asking because we've seen this approach used effectively another IL.
IL two variant trials, yes.
I'll turn it to Ken to answer that very simply they were not there was no.
Pre medications no prophylactic medications used.
Okay got it and final question for me just with respect to the other cue 100 series immuno stats.
Do you see any risk but.
If there are higher based on prevalence let's.
WT, one specific T cells could that potentially translate to a narrow therapeutic window.
Based on the different antigen specificity and.
Is there any preclinical evidence to suggest that you can safely.
Dose different.
Q1 hundred in immuno stats.
Targeting different different tumors without without seeing dramatic safety defenses.
Yes, we don't anticipate that Mark and that's much of that is actually based upon some good preclinical data, including in for example, with Q1 or two that targets WT. One we see the induction and expansion in HLA <unk> transgenic mice as we showed in that slide and we will continue to expand upon this.
As we release data towards for the rest of the year.
That expansion is significantly higher when you compare it to Florida for example, what we could achieve with the seven specific inducing seven specific but in this case for whatever reason the precursor frequencies in the baselines tend to favor WT, one and with no sort of observations.
If any growth sort of safety or tolerability issues. So we think again coming back to how the IL two was selected.
That is quite relevant to the TCR engaged population.
In this case when you've got ranges, where that population is skewed towards the higher or.
Bundle again that tends to be can be controlled quite quite safely at least with the early evidence we have so.
Although we keep an eye out on that amount the data so far supports that we should be able to move in.
With a great degree of confidence.
Perfect. Thank you so much for clarifying and thanks for taking the questions. Thank.
Thank you Bob Thank you Mark.
Thank you. Our next question comes from Stephen Wiley with Stifel. Please proceed with your question.
Yeah. Good afternoon, thanks for taking the questions.
Maybe just one on the update that you guys had mentioned was planned for citizens should should we expect to also get some preliminary.
Dose escalation data from the <unk>.
<unk> combo cohort.
At that time as well.
Yeah, Thanks, Steve Kent do you want to take that.
Yeah. Thanks for the question I think.
We'll have some data to see.
About that as well as certainly later in the year.
<unk>.
Finished cohort one we're dosing cohort two so we're and we're following those patients so.
We expect news yeah.
Okay and then.
If you could just.
Expand a little bit.
Channel strategy that you're I guess now speaking to an end.
When you think about the path forward for mono therapy.
How do you I guess juxtapose that approach I E.
Single arm response rate based.
Endpoint versus something whereby youre looking at.
A comparator arm or maybe you know best supportive care or.
Physician's choice of palliative chemo.
And in addition to generating that response rate data, maybe having a backstop.
<unk> event, driven data in the form of either PFS or OS, which seems to be encouraging at this point.
How do you think about the execution of something like that.
Relative to just kind of the traditional monotherapy response rate based approach.
Well fantastic question.
And really protective.
And we're clearly going to have to go to the FDA to get.
Sign off on any trial, we do as you know there is.
Certainly no.
<unk> third line of therapy, so it would be our preference.
You certainly do a single arm study.
Based on.
Clinical benefit rate as well as overall survival and just power it with enough patients.
For example, just continuing on the <unk>.
Expansion phase study.
And just power it that way.
If the.
The FDA requires us to do a comparator arm.
I think it's going to be difficult.
You'd be asking to randomize to sort of best supportive care.
Or best Palliative care, which is never very exciting for patients and.
Thank you.
The FDA has.
As you know struggling with what to do with single arm studies right now, but Theres also a general consensus that if patients don't deserve to be randomized to care that is not going to extend their life. So I think we have a really good chance.
During a single arm study.
And we're going to go to the FDA with that idea.
Okay, and so when you speak to I guess powering a single arm study for something like survival is.
Would that be compared against a natural history arm I'm just trying to understand what you would be powering against in the confines of it being a single arm.
So again, a really good question and I think if you look at.
The data from the survival data from single agent <unk> second line.
Or any of the checkpoints second line in <unk>.
Head and neck cancer, I think we'll be able to use those as a comparator.
Now as a traditional comparator and I believe that.
If we say that we're going to increase that survival.
A significant percent that we will.
That will be compelling to the FDA.
As Susan mentioned, if I can also just add that that I can.
Ponant the regulatory strategy that is gaining further traction maybe to present to FDA. If there is pushback on just a single arm expansion the use of real world data or a synthetic control arm or at least a fractional synthetic control arm. So so there are opportunities in the setting where it.
Really close feasible to do a good randomized trial, where FDA will work with the sponsors to come up with.
Our powering of our sample size.
Synthetic control arm.
Acceptable.
Okay. Thanks for taking the questions.
Thanks, Steve Thanks, Steve.
Thank you. Our next question comes from Tom Shrader with <unk>. Please proceed with your question.
Hello, Good afternoon. Congratulations I had one question on this interesting OS study or OS signal Youre seeing in early patients.
And if you're wondering if you're saving the cincy you just tell me, but is there any structure to that because it didnt. Some of the earliest cohorts patients got very little drug. So is there any correlation with this effect with patients that actually got significant amounts of treatment.
Treatment.
So thanks for the question and what I can say is that it's too early.
For us to talk about the later cohorts.
We just don't have enough deaths yet to know.
So.
I think that is as good as the answer as I can give you we were able to look at the first nine patients, even who got a whiff of drug.
And we were able to sort of look very preliminarily at a median overall survival.
We just don't have enough data on the later cohorts to talk about it.
Okay and then a question on slide 19, where you have this very long response, where the patient has I don't know three months of stable disease, how literally can we take that line. How noisy is that is this really a patient that at four and a half months the tumor starts to.
Dissolve further and then maybe for a niche is there any mechanism you can think of that would do that would you ever see that with something like PD one.
So firstly.
I'll, let cliff can then matteo on sort of the clinical question. Tom because these are all hard metrics Kennan Mackay. If you want to just comment on the tumor measurements in slide 19, yeah. So thanks.
Thanks.
Those are resist criteria those are measured.
At the site. So we have nothing to do with those measurements and what we've seen is that with the latest measurements.
That's it.
Tumor shrink even more than it is.
Previously.
This is a patient that we're following two lesions in and we're seeing a response in both lesions.
And certainly our niche can.
Talk about the biology of that but you know.
Again with the.
With immuno therapy as it has time to work you have a balance of necrosis fibrosis.
Well as killing of tumor cells going on.
So.
Very encouraged and this is one of the reasons why you know we really wanted to keep patients on study who were having some clinical benefit to give them time to have potentially these kinds of results come in so I feel really.
Just a fight and putting that amendment in two.
To allow us to allow our investigators to keep patients on.
Even though their tumors are equivocal, but if they are clinically benefiting.
Matteo do you want to add anything before a niche.
Talks.
I think that covers it quite well with.
With regards to the mechanism.
I think we're learning more and more of that to different immunotherapies have a kinetic symbolic friedman.
Treatment effect.
A bit more prolonged or unique and again, we could hypothesize that there's you know apple upon loops of increases in T cells that are <unk> specific that occur as the tissue tumors being killed in S. Antigen goes into the antigen presenting compartment did then re stimulates.
And the T cells, but but again, it's just very reassuring to see a deepening confirmed.
Jack give response in this patient.
So Tom just mechanistically the several axis, we believe could be operational which is why I sort of try to highlight as you've seen in this patient in the first scan which is six weeks. After two doses, you'll see about a 45% to 48% reduction in that range, which is now reaching 60 close to 60% patient has been dosed every three weeks, we see a nice uptick of <unk>.
<unk> specific T cells, but one of the reasons, we highlighted and cases as you have the.
So do you have the immune system responds certain other elements could be operational including T cells, including NK cells, including the fact that the IL two is active and tranche, which is one of the reasons I've mentioned there could be other allergenic determine.
Visit fees that we may be influencing and this is one of the reasons don't because of this guidance of observation and the histology that Matteo showed you with the Grand Zombie positivity pre and post biopsy with the Neo Adjuvant study becomes really really exciting for us where we will have tumor tissue from every patient pre and post blood pre and post to be able to make these kinds of.
Hard assessments, including til infiltrates, including the specificities that diversity in the phenotype. So we think that they're a multimodal operational elements of the immuno stat platform that must be appreciated and then we've got to look at this with a wide set of set of eyes here.
Okay. Thanks for taking a tackling a tough question.
No no no very potent and thank you Tom.
Thank you. Our next question comes from Brian <unk> with Baird. Please proceed with your question.
Hey, good afternoon, everyone. Thanks for taking my questions I guess I just have some questions sort of on how you guys think about patient selection I'm, starting with one O one.
Based on the early data that you have so far is there any sort of biomarker.
Does it kind of defines a subgroup that that had some level of predictive response and if not is there any subgroup that you kind of think in the registrational pathway looks particularly attractive.
How do you think it would be generally a more challenging subgroup because of that maybe has a lower hurdle, but you would still expect 101 to work well and then likewise with when you think about the Q1 O two program.
It was a broad range of CE, mark indications applicable here, but we'd be doing any baseline screening to select for WT one expression.
When you get that study kicked off thanks.
And you want to take that yeah. So I.
I think at this point.
Don't have a biomarker.
To choose what I think the power.
This is is that I'm not sure we need one.
Think that.
The mechanism of action is such that and delivering attenuate.
Attenuated IL two stimulation right to the appropriate T cells.
Aggregates the need to worry about.
Subgroups of patients and in fact, we really don't want to parse out.
Them, if we don't need to and at this point I don't see a need to do that.
Of course, as the trial matures and we're looking at.
Data for example will be following patients for circulating tumor HPV data.
DNA.
That may give us a marker of.
Who might benefit in and as well as how folks are responding in clearing that.
And we've got some other biomarkers. We're looking at also but my hope is that we don't need one.
Yeah.
And for one or two do you want to just comment on the WT one expression.
So yes, sorry so.
Again for WT one.
We will be doing.
Again, HLA O to O. One patient and then we are working right now with the FDA and our IND filing.
To choose the very specific.
Assay, where patients will have some level of WT one expression.
Different studies that have used WT, one is vaccines et cetera have used different.
The criteria for enrollment.
Can say right now is that we.
<unk>.
We intend to have a very liberal enrollment policy as far as W. T. One expression on the tumor tissue goes.
Great. Thank you that's helpful. Yes.
Thank you. Our next question comes from sheet Guang shoe with Bahrenburg. Please proceed with your question.
Hi, good afternoon, Thanks for taking my question.
Just to ask about the the registration path you guys laid out on the slides, particularly for the PD L. One neck of their patients.
Just wondering what what are you thinking in terms of getting the trial Rami.
The trial design and also.
As far as I know acquisitions, usually chemo to treat treat at these type of patients I Wonder have you considered maybe combine your drug but with chemo.
So around a frontline trial, thanks very much.
For those questions. So in the third line setting.
Patients will have received a platinum combination therapy.
Often with or without Cetuximab.
As for first line therapy or second line therapy, many of those patients in the adjuvant setting or neo adjuvant setting will have also seen a platinum or fiber a few based regimen.
As you know.
<unk> with chemo is quite effective in the <unk>.
First line patients and so what we're expecting is that in the third line setting.
And the second line patient with TPS scores less than one patients will have already seen chemotherapy and again there is no approved chemotherapy.
For second and third line patients beyond.
The platinum.
<unk> combination therapy platinum platinum combination therapies. So we're not in the short term expecting too.
Certainly in second and third line.
Combine cue 101 with chemotherapy at this point.
What where we will explore with the FDA is.
And we don't know what they will say about this yet but again.
Patients, who don't have a cps score greater than one are not eligible for <unk>.
Simply doesn't work we do believe however, given the mechanism of action of cue 101 that.
Our drug will be just as.
Effective in those patients.
And so we would like to include them.
As part of a.
A third line study.
And we will present that idea to the FDA and we think that.
There's a good possibility they will allow that given all of the data I just all the things I just said.
So that's our strategy right now.
Got it.
Thanks very much.
Thanks, Steve Thank you.
Thank you there are no further questions at this time I would like to turn the floor back over to management for any closing comments.
Alright. Thank you. Thanks again for your attention on today's call and as always we look forward to providing further updates as data continues to emerge and stay safe.
Thank you.
This concludes today's conference you may disconnect your lines at this time. Thank you for your participation.
Yes.
Yeah.