Q3 2022 Cue Biopharma Inc Earnings Call
Greetings and.
And welcome to the cue Biopharma update call.
At this time, all participants are in listen only mode.
A question and answer session will follow the presentation.
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Please press Star then zero on your telephone keypad.
As a reminder, this conference is being recorded.
I would now like to turn the conference over to Dan to say cue Biopharma Chief Executive Officer. Thank you Sir please begin.
Thank you and good afternoon, everyone before I begin I would like to remind everyone that you have the slides in front of you that you need to operate manual manually and we will notify you what slide we're on.
Joining me on today's call.
As Dr <unk>, President and CSO.
Dr. Ken.
Our acting Chief Medical Officer, and Dr. <unk> <unk>, our senior Vice President clinical development as well as Kerry <unk>, our Chief Financial Officer.
The conference is being recorded and will be available on our website for the next 30 days.
As a reminder.
And as shown here on slide number two.
<unk> and <unk>.
Overview may contain some forward looking statements in any forward looking statements made during this call represents the company's views only as of today November 14 2022.
Our agenda for today's call is shown on the next slide slide three.
I'll begin by providing an overview.
All of our competitive and strategic positioning based upon data from both our monotherapy trial of cue 101 as well as the data just recently reported at <unk> from our cue 101 in Keytruda combination trial with <unk>.
And Karen will provide.
This a review of this data in further detail momentarily, but.
First I want to provide context pertaining to the underlying implications and importance of the datasets observed to date.
As you are aware the ultimate promise of immunotherapy is to enable the intrinsic potential of a patient's immune system to recognize and kill cancer.
We believe through our representative data generated from both our monotherapy trial and combination trials of cue 101, our IL two based cue 100 series is now well positioned to become a first in class selective T cell engagement and best in class IL two for cancer immunotherapy.
Therapy.
Here on slide number four.
The data bolsters, our belief that the demonstrated mechanism of action and resulting activation and amplification of cancer specific T cells.
Well mechanistically complement and enhance therapeutic benefit derived from checkpoint inhibition, such as PDL one inhibitor keytruda.
We believe the violation of data.
From both the monotherapy and combination trials supports.
Central thesis of selective activation of cancer specific.
Specific T cells, while avoiding systemic immune activation will enhance.
The desired anti tumor efficacy.
The recent data presented at city positions us well to push forward and potentially transform cancer therapy, where patients own immune systems can be harnessed to the fullest extent to eradicate cancer.
I'm now going to turn the call over to a niche who will provide a brief synopsis and overview of the key mechanistic features of our selective T cell engagement. The IL two based cue 100 series and I will then turn the call over.
To Canada Matteo to review the supporting efficacy data.
That has emerged from the monotherapy trial and provide an update from our recent <unk> presentation pertaining to the current efficacy data from a combination of cue 101 with Keytruda in frontline HPV positive head and neck squamous cell carcinoma patients.
<unk>.
Thanks, Dan and welcome to all listening to this update.
As noted in the next slide.
I appreciate the fact that selective activation of tumor specific T cells is central to successful outcomes for cancer immunotherapy.
Wherever there are biological constant that nature has imposed to that must be considered when thinking about tumor specific T cells. One the frequency of tumor specific T cells in the patient is extremely low greater than 99, 9% of T cells in a patient have no relevance to Kansas. So how does one go about select.
Reactivate and tumor specific T cells, while sparing the broad activation of all other T cells and other biological constant is the fact that the only unique marker on an anti tumor T cell is the tumor specific T cell receptor or TCR.
There are no.
Cell surface markers that exhibit an absolute fidelity to the antitumor T cell repertoire as the tumor specific TCR for example, PD one expression is a shed phenotypic marker or <unk> expression is a shed lineage marker, but neither are unique to an anti tumor T cells, hence to exploit this unique selectivity we've.
The immuno stat platform to harness the TCR specificity to activate tumor specific T cells. We believe as supported by our clinical data that this approach is differentiated in terms of both safety and efficacy outcomes over other modalities that attempt to activate the immune system in a non selective manner. The next slide slide 6%.
<unk> the cost structure of an immuno stat molecule derived from our IL two based cue 100 series, which is a major focus of todays presentation as shown here. The cue 100 series immuno stats harnessed. The TCR selectivity, we have a stabilized peptide HLA molecule to target and affinity attenuated IL two variant selectively to tumor.
<unk> specific T cells, the core signaling via the PCR and IL two receptors on the REIT antitumor T cell results in T cell activation and expansion in contrast of this molecule in counters. The vast majority of irrelevant T cells in the patient that has a greater than 99, 9% of irrelevant non tumor specific T cells the attenuated.
IL two on its own is very weak hence with this unique bias. We have created a therapeutic index, where IL. Two we are selective focusing on tumor specific T cells. Overall other cells. This strategy also forms the mechanistic basis for targeting numerous other activation signals, including other cytokines such as IL 12.
15.
'twenty, one et cetera.
Additional aspects of the cue 100 series are important to appreciate one of the primary core IL. Two framework is largely conserved between different therapeutic candidates. The primary difference from one therapeutic candidate to the next is the 9% to 10 amino acid T cell epitope that depicted by the yellow circle in the diagram on the slide.
Due to this convert structure, we believe the clinical proof of concept with our first clinical candidate cue 101 has de risk. The entire platform. This conclusion is supported by the IMD approval by the FDA earlier this year for our second clinical candidate cue one or two based on the clinical safety data from cue 101, we did not need to pay.
Any additional IND, enabling toxicology studies and were allowed to start the Q1 or two trial at a make per kg dose, which is a clinically active dose from our experience with cue 101, both cue 101 in Q1 or two on 99% sequence identical except for the 9% to 10 Immunoassay T cell epitope Q1.
<unk> targets of T cell epitope from human Papilloma virus for HPV, driven cancers, such as head and neck cancer, while Q1 O two targets of T cell epitope wilms tumor one or WT, one and on coffee Atlanta, Jill widely expressed by many solid and Hematological cancers. The other key aspect of the cue 100 series immuno stats pertains to that.
Favorable stability and manufacture ability metrics as a biologic platform. These are antibody FC fusion proteins that follows stablish manufacture ability and CMC protocols for many decades of commercial monoclonal antibody production the shelf stability for the cue 101, GMP drug product our first clinical candidate.
Greater than 36 months, which underscores the robustness of rational protein engineering, let's move to the next slide slide seven based on the generation of a therapeutic index for IL two by selective targeting of tumor specific T cells. We believe that the cue 100 series has the potential to be the best in class IL two modality for cancer immunotherapy.
It will be as shown here the improved safety and tolerability, coupled with the anti tumor T cell selectivity possessions that cue 100 series in a significantly different bracket when compared to all other IL. Two variants that are being pursued none of which are selected for the tumor specific T cells. In fact, most of the focus of other IL two veterans.
Has been on modulating IL, two receptor interactions, but little thought towards anti tumor T cell selectivity. This lack of biological relevance will continue to generate sub optimal clinical outcomes as recently evidenced with the clinical datasets.
From the recent trials from the Pegylated IL two in the not Alpha IL two modalities.
Finally, let's move to slide eight that highlights supportive data for biological selectivity and activity of the IL two based cue 100 series. The panel on the left shows selective engagement of the cue 100 series immuno stat with an antigen specific T cell. These data were generated by the lab of Dr. Michael Industrial at University of walks.
Dr. <unk> has been a pioneer in describing the T cell immune synapse that leads to downstream activation and effector function as shown here. The cue 100 series immuno stat only forms and immunological synapse shown in green with the antigen specific T cells were enforced the TCR in IL two signals are operate.
The same molecule with an irrelevant T cell as shown in the bottom left panel demonstrates no immune synapse in absence of TCR engagement. The middle panel shows selective expansion of tumor specific T cells from primary human blood samples, while no off target effects are noted with irrelevant T cell specificity. This.
Is exactly in line.
With the molecular design of the drug that is selective expansion of tumor specific T cells, while sparing all other non specific T cells. The panel on the right shows intra tumoral infiltration and expansion of tumor specific T cells and in HPV driven cancer model in mice note that in this study not many T cells are evident in.
The vehicle treated mice or in mice treated with the anti PD one antibody alone in contrast, a significant number of T cells present after monotherapy with cue 100 series immuno stats and this population is further enhanced in combination with anti PD one antibody treatment. We believe this ability of the cue 100 series.
Molecules to turn a cold tumor hot but selectively activating the right T cells is a key differentiating feature of our drug design similar observations are also evident.
The early emerging data from the ongoing mechanistic clinical trial with cue 101 in a new adjuvant setting in locally advanced head and neck cancer patients with that background on our differentiated mechanism for IL two targeting I'd like to now pass the call to <unk> and Matteo <unk> to share the exciting clinical data from the ongoing <unk>.
Files with head and neck cancer patients with our lead clinical candidate cue 101, Ken.
Thanks.
As shown on the next slide data from the ongoing clinical trials with cue 101, as monotherapy and in combination with parallelism map have provided clinical proof of concept or POC and derisking of the immuno stat platform. We're pleased to be presenting our updated data from the ongoing cue 101 phase.
One trial as both a single agent monotherapy in third line and beyond patients as well as the encouraging emerging data from the combination study with <unk> in first line patients as previously consistently stated by US We believe Q1 hundred one's mechanism mechanism of action.
As evidenced by the ongoing data generated to date provides effective and tolerated dose levels, enabling selective stimulation of tumor specific T cells.
Current head and neck cancer is a tough incurable disease.
The data we have observed throughout the monotherapy trial and enhances our confidence that Q1 on one stimulate a cancer specific T cells in a subset of these patients with a resulting anti tumor effect.
Furthermore, and more importantly, we continue to observe an evolving trend of enhanced survival.
Key observations in patients treated with cue 101 monotherapy in third line and beyond include as detailed on slide 10 demonstration of a single agent and demonstration of single agent anti tumor.
Efficacy evidenced by resist PR and durable stable disease in third line and recurrent metastatic head and neck squamous cell carcinoma.
Ah.
Median overall survival benefit emerging from the survival follow up in the <unk> cohort.
The robust data in Q1 hundred one's activity in monotherapy and in combination with <unk> Mab has triggered the granting of fast track designation status for the treatment of patients in both first and third line settings.
As shown on slide 11.
101 demonstrates well behaved pharmacokinetics with low inter patient variability at the recommended phase II dose for Migs per kit.
Exposure is maintained throughout multiple cycles of treatment without any.
Attenuation of PK parameters, consistent with a lack of clinically relevant immunogenicity.
Q1 on one treatment results in sustained increase in NK cells.
Positive attribute of an anti tumor response.
The NK cells may assisting tumor killing.
And as you can see in the lower left panel with only a modest and transient increase in T regs.
Shown in the Middle panel, we observed observed robust expansion of tumor specific <unk> reactive T cells in the peripheral blood of patients as early as one week after administration of cue 101.
On the right panel paired and post treatment biopsies demonstrate an increase in tumor infiltrating T cells in tumor necrosis.
In addition to the favorable PK and PD just described.
Patients with advanced.
HPV positive head and neck squamous lung cancer.
We are experiencing in patterns of clinical benefit.
Three examples are shown in the next slide slide 12.
Patient experienced a durable partial response within approximately 60% reduction in tumor burden that was evidenced starting at six weeks after two.
Two cycles of cue 101, and lastly, close to one year patient remains on treatment at the present time is at stake.
Stable disease with tumor burden reduction of approximately 20% observed at week, 48, and notably complete disappearance of HPV cell free circulating tumor DNA in the blood observed at week six and maintained.
Taxable HCV CF DNA is an increasingly recognized biomarker of disease activity and suggests the possibility of a pathologic complete response and cure this patient who will likely have a surgical resection of their solitary cancer lesion early next year.
Patients see has experienced tumor reduction.
Prolonged period on the drug where no resist based objective response was initially observed by imaging and this patient is treated with Q1 and wanted to mix per gig. We can see that the first several months appear to demonstrated tumor growth even beyond the 20% threshold used by resist criteria. However.
Based upon the overall clinical status the patient continued on treatment after approximately six months to tumor began to shrink in the patient.
It remains on therapy 14 months after starting treatment with cue 101.
This observation consistent with observations made by others demonstrates that the kinetics of T cell anti tumor activity may manifest over a long period of time.
The next slide slide 13, conveys our ongoing survival swimmer plot for the 20 patients dosed at the RP <unk> four megs per kit.
The emerging Kaplan Meier estimate of median of a median overall survival of greater than 13 months compares favorably to the survival of approximately eight months observed in patients treated in the second line in keynote the keynote 40 trial of <unk>.
As any experienced oncologist understands the survival.
Treatment is expected to be less as the disease is further developed and become more unstable.
Our continued evolving data supports the premise that treatment with cue 101 is clearly trending to increase survival and the third line setting for patients with head and neck cancer.
This data has encouraged our principal investigators and they are certainly in line with our position that this provides us with a promising path forward to a registrational trial.
The demonstration of monotherapy activity bolstered bolsters, our belief that we should see complementary mechanistic effects in combination with <unk> as a reminder, the data from <unk> treated in monotherapy clearly support the cue 101 increases the number of antigen specific T cells.
It is likely that these T cells will have greater freedom to kill with.
With concurrent inhibition of the PD, one pathway a major mechanism used by cancer cells to prevent immune mediated killing.
I'll now pass the call to Matteo.
Teo will provide an overview of the exciting emerging data and clinical efficacy of cue 101 in combination with Penn Brown Matteo.
Thanks, Ken.
Shown on slide 14, even at our starting dose of one Meg per kg, we observed a patient with durable stable disease at two milligrams per kilogram, we observed a patient with durable stable disease and the patient with a deep partial response, who continues on therapy today.
The presumed a recommended phase II combination dose we have not only not observed any dlt's, we observed a 40% objective response rate.
For now confirmed partial responses and another four patients with stable disease that are currently being monitored on the trial. This compares favorably with the reported overall response rate of single agent <unk> of 19% in the first line treatment setting as.
<unk> in the keynote 48 trial, let me show you. Two example of these partial responses slide 15 shows the patient from cohort two demonstrating a decrease in all four of their target lesions, including two liver lesions as seen on the two scans on the left.
I want to emphasize that this is not just shrinkage in lymph nodes, but shrinkage of visceral metastatic tumor disease in the liver.
On the upper right side, the graph depicts the absolute measurements of the four target lesions.
With the best overall response of approximately seven 8% to any oncologists. This is a significant and meaningful response. This patient has also demonstrated a clearing of the circulating cell free HBV DNA, which is ongoing as mentioned before circulating cell free <unk>.
<unk> continues to be developed and used by our principal investigators as a potential surrogate.
For response.
As slow as shown in slide 16, one of the patients with a confirmed partial response from cohort three.
<unk> demonstrated reductions in all four target lesions, including two parenchymal lung lesions.
Well as a clearing of the circulating cell free HBV as you can see on the scans on the left the target lesions three and four both are very substantial.
<unk> metastatic disease lesions in the lung.
Decrease in size by a greater than 60%.
Absolute measurements of the four target lesions are depicted in the right upper panel.
And as we have seen in the last patient this patient completely clear their tumor DNA from the blood at a time concurrent with the observed resist response.
And the next slide Slide 17, we see that all of the patients treated in the combination trial are still alive five of whom have already passed the median overall survival observed in the keynote 48 trial, which was 12 three months.
We also anticipate an increase in progression free survival as the data from the four Meg per kg plus Pampa lithium mab cohort matures taken together. These are the observed doubling of overall response rate, 40% compared to the historical 19 presents.
<unk> observed in keynote 48 with <unk> monotherapy, along with an increase in median PFS will expand patient reach and may provide an attractive therapeutic option for patients with recurrent metastatic <unk>.
Head and neck squamous cell carcinoma in the first line.
Setting.
A high level perspective of study designs to support approval of both monotherapy and combination with <unk> is presented on slide 18, we are excited by the preliminary data in the ongoing monotherapy and combination trial and plan to get clarity on the Registrational path too.
Approval for both lines of therapy.
The recent granting us fast track designation further underscores our confidence in realizing successful regulatory interactions.
Im also happy to report that we have treated our first patient with cue 102, which targets wilms tumor one positive tumors and the trial that is enrolling patients with advanced colorectal gastric pancreatic and ovarian cancers as shown on slide 19, Q1 O. Two in Q1 O one shared 99%.
<unk> immuno accurate amino acid sequence identity.
This enabled us to significantly decrease the development time and cost of cue 102, as we were not required by the FDA to repeat IND, enabling toxicology studies for Q1 or two and we are also able to initiate the phase one dose escalation study at one Mig per kg the dose at which we are.
Observed clear signs of biologic activity with cue 101.
As slide 20 shows we are performing the Q1 or two dose escalation study in colon gastric pancreatic and ovarian cancers. This design offers us the ability to do monotherapy expansion studies in any or all of the indications being evaluated in the dose escalation phase of the trial the trial is <unk>.
Actively occurring and we will be open at 15 sites around the United States. We plan to present additional data at an upcoming medical meeting I will now turn the call over to a niche to talk more about our pipeline our niche.
Thanks, Matteo and moving on to the next slide as you heard from the clinical update and as shown on this slide we believe the clinical Derisking by cue 101 has essentially derisked our entire platform as noted by Matteo. The recent nine the acceptance for Q1 of two targeting wilms tumor one underscores the strategic advantages of platform.
Derisking accomplished by Q1, and one which also highlights the resource time and operational efficiencies. Furthermore, we believe the modularity of our platform coupled with the clinical validation positions us to generate a rich repository of therapeutic molecules targeting many kansas. Some examples of additional tumor antigens that can be effectively tal.
Such as mutated K, Ras or major four or claim are shown here. Furthermore to extend the application of our platform to incorporate multiple T cell epitopes or even personalized neo antigens. We have created the neo stat framework with an empty HLA molecule to which we can chemically conjugated Andy.
Given tumor.
Tumor epitope.
Again, the core IL two variant and valency is conserved the neo stat platform expansion realizes significant time and cost efficiencies by having an off the shelf approach to selectively target multiple tumor antigens across many Kansas as one evaluates the potential of IL two for cancer immunotherapy.
We believe our platform is crack the code for selective targeting of this important cytokine to the tumor specific T cell repertoire with that I'll now turn the call over to Kerry to give a brief financial update Kerry. Thanks, Anish, turning now to slide 22, I'd like to provide a brief update on our financial results for the three months ended September 32012.
Detail the company reported collaboration revenue of approximately $68002 4 million for the three months ended September 32022, and 2021, respectively.
Search and development expenses were $7 6 million and $11 3 million for the three months ended September 32022, and 2021, respectively. The decrease is primarily due to increases in laboratory and <unk> manufacturing costs employee compensation licensing fees and rents.
General and administrative expenses were $3 5 million and $4 1 million for the three months ended September 32022, and 2021, respectively. This decrease was due primarily to a decrease in stock based compensation and.
Professional and consulting fees incurred during the third quarter of 2022 as compared to the same period in 2021, we ended the quarter with approximately $59 1 million in cash cash equivalents and marketable securities and working capital of approximately $51 5 million earlier today, we announced that we had entered into a securities purchase agreement lets start.
A credit event at <unk> at $30 million private investment in public equity or a pipe financing, we believe our cash and cash equivalents and marketable securities as of September 32022, along with a $30 million that we received from the pipe financing will allow us to support the development of our immuno stat platform, including the <unk>.
Development of Q1 online and Q1 O two into 2024, I will now turn the call back over to Dan for closing remarks, Dan.
Yes, Thanks, Gary.
With the recent financing extending our runway upon closing combined with the support of them.
Promising data from our ongoing clinical trial.
I want to focus on core strategic initiatives to further enhance our competitive positioning to optimize shareholder value.
Clinical data recently reported at <unk> enhances our confidence and the breakthrough potential of our platform and the transformative nature of our approach to selectively modulate disease relevant T cells directly in the patient's body.
We believe we are now very well positioned to take the company to the next level and emerge as a leading provider of effective and well tolerated T cell engages with the potential of transforming cancer therapy.
In the near term.
We're focused on several core corporate development catalyst and strategic initiatives to further enhance our competitive positioning.
Primarily primary among these core initiatives the following milestones to enhance shareholder value as shown on the next slide.
With cue 101, monotherapy expansion cohort and third line and beyond refractory or metastatic HPV positive head and neck cancer patients.
We will have mature median overall survival data by the end of this year with a potential registration trial being defined.
Next year.
With cue 101, plus <unk> combination expansion cohort, we anticipate reporting preliminary overall response rate in the second quarter of next year on the full 20 patients with a potential registration trial being defined in the second half of the year.
We are highly encouraged by the data reported at city on the first 10 patients and look forward to reporting on the full 24 Meg per kg cohort.
Again to remind you we believe the data reported to date supports the premise that cue 101 as representative of the immuno stat platform cue 100 series.
Demonstrates the potential of expanding patient reach and therapeutic benefit of checkpoint inhibition, placing us in a strategic position for corporate partnering.
The Q1 O two monotherapy dose escalation trial is ongoing.
With Q1 of two targeting wilms tumor one expressing cancers.
The evidence of clinical activity should be a catalyst for further validation and value enhancement of our platform data from this dose escalation should be reported.
By mid 2023 with significant potential market opportunities and WT, one positive cancer indications.
We believe the differentiated therapeutic potential of the IL two based cue 100 series as evidenced by our current datasets will further catalyze significant business development and corporate development opportunities for pipeline expansion addressing hematologic and solid cancers, we look.
Forward to providing ongoing updates in the coming months and want to thank our shareholders for their support and shared vision and the potential of cue biopharma to transform the treatment of cancer.
Want to extend our gratitude to our employees our board of directors and most importantly, we want to thank the patients and their families for participating in our trials.
Thank you all very much for your attention and interest and I'd like to downturn the call back to the operator for questions operator.
Thank you, Sir ladies and gentlemen.
Now begin the question and answer session.
Ask a question please press star and then one.
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The first question, we have is from Ryan Benjamin from JMP Securities.
Hey, good afternoon, guys. Thanks for taking the questions and congratulations on.
On the data update in May.
Maybe just to start off can we talk a little bit, especially in the combination study what are the.
The typical treatments that youre seeing kind of post progression.
And are you seeing in these first 10 patients any sort of recycling of checkpoint inhibitors.
And potentially getting a subsequent response in patients who maybe didn't have that before.
So this.
This is Ken thanks for the question so.
It's we don't know.
What's going on with those.
<unk>.
Dana.
We're collecting but.
We really can't give you an update on what other therapies they might be getting afterwards.
Across multiple sites.
There is no specific regimen that these folks are going to.
Got it.
And then Oh.
Either for the monotherapy or.
The combination study I don't think I saw this number but I'll just ask it anyway do you have a median duration of response.
You know for either of those two.
No we don't we haven't.
Calculated that because.
We wont calculate that until we get the final survival data in the monotherapy and it's just too early to do that in the combo.
Got it.
And then just switching gears real quick to the Neo Adjuvant study can you talk a little bit about.
You know maybe how many patients have been enrolled and have you been.
Successful in obtaining biopsy samples and is there any color that you might be able to provide from sort of the initial.
Or any initial takeaways, yes, so so.
The Neo adjuvant study is really a spectacular opportunity for us.
To really examine in the tissue itself the effects of Q1 on one therapy. So we're obtaining in the new adjuvant setting pre and post.
Treatment biopsies, we've treated close to 10 patients to date.
Preliminary data that we have in these paired biopsies demonstrates some of the findings that we've observed in patients I E. We have observed increases in NK cells pre and post treatment. We also observed findings consistent with the increase in pills or tumor.
Infiltrating lymphocytes that we've observed in the paired biopsies obtained in the patients in the cue 101 O one trial.
Terrific. Thanks, very much for taking the questions and I'll jump back in the queue.
Thank you Brad.
Thank you next question, we have is from Stephen <unk> from Stifel. Please go ahead.
Yes, thanks for taking the question.
Maybe just to follow up on the Rins question. I know you don't have a median duration of response for the combo just yet but.
Do you have the duration of response from.
Best responding combo patient.
I believe is no longer ongoing therapy.
If I can mention here and really the duration of response had monotherapy is 42 weeks so to confirm PR that we observed in monotherapy at Ford mix per gig is really a very durable response I think if we look at the Spider plot. So slide.
<unk> 17 from the I am sorry swimmer from slide 17 in the combination therapy.
What clearly is evolving is.
An increase in progression free survival and so if you look at the length of time that patients remain on therapy.
And if you had to sort of eyeball median PFS it really appears to be perhaps somewhere between six months and seven.
Seven months.
So in contrast to the PFS that was observed in keynote <unk> <unk> 48 of three months. It really appears that there is a differentiated signal with regard to progression free survival and one can infer to come back to your question regarding the mean or median time on treatment I think PFS is a very good sir.
<unk> for that because our patients tend to stay on treatment.
Without progression because the combination of Q1 O. One in <unk> is being so well tolerated.
Okay.
And then.
What can you say about where you are on the development side with India Stat.
And to the extent that you've you've de risked the cue 100 series.
How do you think about advancing neo stat versus maybe just swapping in a different.
Allele variant.
Of the cue 100 series and trying to leverage some of the progress and the Derisking that you've made to date on the platform.
Yeah, Hi, Steve This is a niche.
Very very good question. So there's two ways, how we are thinking about this Steve obviously.
<unk>, where we have very strong confidence of other <unk> are coming in that select for the tumor epitopes on <unk> is a very good example of that.
HLA a 11 three for example, there's very good data.
That's emerged intuitive over the TCR T based approaches that are being pursued.
<unk> mutated <unk> <unk> variance so in that case it makes very good sense and that's what we've done where it makes sense to go forward with a different allelic variant that gives us confidence of targeting that particular epitope from a primary tumor driver.
The Neo stat framework on the other hand has been created on <unk>, which essentially just gives us excellent continuity for the pipeline because of the derisking and the nature of sort of impression we already have from one or two for example, so this is another analog that's how we look at it except that the time to generation of the active drug product is going to do with <unk>.
Statuary lesser than making a separate antibody molecule as we have to do with the peptide linker in like 101, 100 to 103 et cetera. So both prongs are being pursued in the neo stat. We've obviously you've seen some of the data where we've had early proof of concept experiments and validation. We're now in the midst of optimizing.
Processes, where conjugation and scaleup, hoping with the with the intention of sort of really moving this towards clinical applications in the future.
Great. Thanks for taking the questions.
Sure. Thank you.
Thank you ladies and gentlemen, just a reminder, if you would like to ask a question. Please press star and then one now.
The next question, we have is from Mark band back from Oppenheimer. Please go ahead.
Hey, good afternoon, guys and congrats on the 60.
Maybe a couple of quick ones for me personally to a clarification.
For Dan.
Around the language of defining potential registrational trials in 2023, both of them for the monotherapy and combo.
By defining the trial do you mean.
The protocol or initiating the trial, but maybe you can just be a little more specific there.
And then another question maybe on the <unk> side.
I'm just wondering if you're continuing to see evidence of clonal T cell expansion in the peripheral blood in the.
Ongoing combination study we saw some of that in the monotherapy part of the study.
It's been a while since I've seen.
Some of those data presented is that been superceded by by the each circulating tumor HBV DNA.
Or.
You know we can we can look forward for more of that sort of analysis. Once you have the floor 20 patient cohort. Thanks for taking my questions.
Sure. Thanks Mark.
Give you a broad overview question response to the first question and then I'm going to turn it over to Matteo and maybe a tail in our niche can take the second question.
Regarding the registration path of reason, we're putting it out is defining as we want to assess do we want to approach both third line and frontline or determine whether we're just going to get a registration path defined meet with the FDA to show confidence in the underlying support of dataset.
And then continue on with the frontline because what.
What we have to assesses how rapidly would a registration path.
Frontline kind of cannibalize the market on the third line. So that's one of the factors we're looking at but the key is for us to define based on the strength of the data meet with the FDA and in defined defining the protocol, but I'll turn it over to Matteo yeah. Thanks, Dan.
It's really an important question and what we really have is a harmonized regulatory strategy.
[noise] mutually leverage the data that's being acquired in monotherapy and the data that's being acquired in combination.
And we have a planned interaction with FDA.
The first quarter.
Of next year, we will really use that as an opportunity.
To get as much clarity as possible with regards to Registrational path for both approval of monotherapy in the third line and beyond as well as approval of the combination therapy in the first slide so so in our experience in my experience in particular, given the strength of a are emerging.
Combination data.
The FDA will be very keen to partner with us to.
To really explore ways that would bring the combination therapy to patients as fast as possible.
If the objective response rate.
40% is.
<unk> continues to be observed in the additional 20 patients.
We will then have a very compelling data set.
To discuss with FDA.
The opportunity of pursuing an accelerated approval based on an overall response rate, which we're currently seeing is twice that of Perm Romano first line.
In the setting of a trial, where we have fully enrolled the cohort power to meet an overall survival co primary so so.
That really is sort of the approach that we're taking will have to decide from a business perspective, whether to pursue both a one and in what order, yes, and just to add on Mark to the question around PD for T cell analysis that is very much planned for the combo, we just haven't.
Executed on that and initiated what we'd like to do a batch analysis with all the samples together as these patients are being recruited just like we had sort of started to do some of that for mono, but I anticipate.
Similar outcomes if not.
Even possibly higher frequencies based on some of our preclinical observations. So we'll share that when we generate the data.
Alright terrific. Thank you. Thank you for taking the questions and congrats on the progress. Thank you Mark.
Thank you. The next question we have is from Brian .
Gordon from pod.
Hey, guys. This is Charlie on for Brian . So I just had a couple of quick ones.
I was curious how we should think about comparing data between the cue 101.
And some of them are.
Other therapies that are in the HSN cc space given.
It's targeting <unk> plus <unk>.
<unk> plus patients like is that do you think that's something that might come up with regulators given the literature tends to see it as having a better prognosis than HPV negative.
And then secondly.
If you could just give some color on how youre thinking about advancing 101, as a mono therapy and what kind of hurdle you think youre going to have to hit in terms of overall response rate that'd be great. Thank you guys.
Okay.
Yeah.
I'm happy to start there.
So with regards to.
The prognosis of patients with HPV positive cancers. In contrast to those that are HPV negative I think you point out.
Relevant observation, it's true that they appeared to do a little bit better at each line of therapy, but not that much better. So we have a host of really experts in HPV, driven head and neck cancer as investigators.
And there is a limited set of subgroup data available in the second line.
If you do look at the four studies, where that sub group.
Alex This is available it appears that they may do better by a month or two okay, not by six months or greater.
And so the treatment effect and the benefit that's emerging in mono therapy.
He is very differentiated fat.
Factoring in.
What you are saying, which is accurate that HPV positive patients may do a little bit better at each line.
Therapy with regards to the registration path for monotherapy and the third line and beyond.
We really have a consensus among experts that.
If we demonstrate okay in the monotherapy cohort median overall survival of 12 months.
And currently as we showed at <unk>. The median OS Kaplan Meier estimate is at 13 three months.
That would really represent a very significant clinical benefit compared to the anticipated survivorship. So in the second line setting HPV positive patients have a median OS of about eight months and so if you do a meta analysis of the subgroup data thats available.
Were observing a treatment effect that goes now.
Beyond 13 months, so again, a greater than 50% improvement so with regards to a registrational trial in third line and beyond given that there is no standard of care, we would envision doing a very efficient trial of cue 101 monotherapy versus investors investigator's choice of chemotherapy.
And we would power it based on the numbers that I've just mentioned.
Fantastic that's very helpful. Thank you very much thank.
Thank you.
Yeah.
Thank you. Our final question comes from Ted can talk from Piper Sandler. Please go ahead.
Great. Thank you very much and thanks for squeezing me in my question.
101 have been incurred and I'm excited about the progress we're making there.
When it comes to one or two can become a fair with us.
Christian is the broader opportunity.
Now that you've de risked the immuno stat platform.
101 in HPV positive head and neck, where could you go with one or two things.
Yes, Thanks Chad.
So the importance of 102 is a new state. It is an analog of 101, it's been derisked from the standpoint of were able to start at Onemain.
Preclinical data on human blood samples from cancer patients. Even then we were able to show significant amplification of targeted T cell. So we're actually going into this with a lot of confidence the importance of wilms tumor one is over expressed in a significant number of solid and.
<unk> cancers.
Including.
Colorectal pancreatic ovarian and.
Glioblastoma for instance.
And we're looking at any activity, we see in this dose escalation phase is going to be a real catalyst in terms of demonstrating the modularity and re affirming in validating. This analog nature is the exact same framework. All we're doing is swapping out the epitope. So it really will reinforce.
So.
Cassette form of being able to swap out an epitope.
Have the molecule active against a different subset of T cells to address various cancers, so I'm going to now hand, it over to Matteo just to elaborate yes.
Yes, so really in a very good question and so clearly you recognize that WT. One is over expressed in it really a large number of cancers and so we decided to initiate development and a small basket of solid tumors focusing on Gi tumors.
Including colon pancreatic and gastric as well as ovarian to really most efficiently achieved several objectives, including demonstrating the safety Tolerability PK PD and a defined population in a trial, where we can also expand and look for.
And in a very a population of a huge unmet need being colorectal cancer.
The activity there is competitive and promising.
We did write the protocol in such a fashion that we can very easily expand into any of the four indications if we see early signals of activity.
And clearly other indications where this is quite de risks as a target include glioblastoma.
As soon as there is some data.
In a small number of patients it would be very easy to amend the protocol and include cohorts of patients including.
And glioblastoma in terms of liquid tumors, there its perhaps most lately.
De risks with with TCR T experience with WT, one is at target and so AML Myelodysplastic syndrome, Theres, a whole family of liquid tumors. So so we really decided to do serve a step wise.
De risk triggered by data investment and expansion into the multitude of addressable indications with WT one.
Super helpful. Appreciate the color.
Okay. Thank you. Thank you Sir.
This concludes our question and answer session I would like to turn the conference back over to Dan <unk> for closing remarks. Please go ahead Sir.
Again, we want to thank everyone for your time and interest in our ongoing progress and we look forward to providing you with updates in the coming months. Thank you again and take care everyone.
Thank you Sir.
Ladies and gentlemen.
Concludes today's conference. Thank you for joining US you may now disconnect your lines.
Okay.
[music].
Yeah.