Q3 2023 Cue Biopharma Inc Earnings Call
Ladies and gentlemen, this is the operator today's conference is scheduled to begin momentarily until that time lines will remain on music hold thank you for your patience.
[music].
Okay.
Good afternoon, ladies and gentlemen, and welcome to the Q by Biopharma third quarter 2020 earnings call.
At this time all lines are in listen only mode.
Following the presentation, we will conduct a question and answer session.
If at any time during this call you require assistance. Please press star zero for the operator.
As a reminder, this call is being recorded today Thursday November nine 2023.
I would now like to turn over the conference to <unk> Chief Executive Officer. Please go ahead.
Yes, Thank you and good afternoon, everyone.
As a reminder, this presentation and discussion is being recorded and will be available on our website for the next 30 days.
Also be aware that the slides accompanying today's update maybe advanced directly by those listening in on the call and we'll notify you of what slide we're on throughout the presentation.
Joining me on today's call is Dr. <unk>, <unk>, our president and Chief Scientific Officer.
Dr <unk> <unk>, our Chief Medical Officer.
And Carrie Ann Miller, our Chief Financial Officer.
As shown on slide number two of the presentation and you 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 nine 2023.
Okay. The next slide slide number three outlines the agenda for today's call I'll begin with a brief summary overview of our therapeutic platform and core competitive positioning which is bolstered in further validated by the recent data update presented this past weekend at Citi.
Ill turn the call over to Matteo who will provide a detailed synopsis of our clinical data from both the monotherapy and combination portions.
The ongoing Q1 O one trial as well as the highly encouraging early signs of clinical activity from the dose escalation portion of the Q1 O two monotherapy trial.
As a reminder, these data are representative of our modular immuno stat platform.
Which we believe has significant potential for broad market applications in cancer, immunotherapy, autoimmune and inflammatory diseases as well as chronic infectious diseases.
After Matteo a niche will provide further details of our platform developments underscoring the far reaching potential of our approach for selective modulation of disease specific T cells and the potential for superior differentiation.
Following a niche carrier will provide an overview of our financials for Q3 and guidance going forward I will then return for some concluding remarks and open the call for questions Alright, Let me first begin by emphasizing our strategic positioning and core competitive advantages.
It's self evident that within the immuno oncology sector, there have been significant and persistent challenges and realizing the full potential of immunotherapies.
Many therapeutic modalities and combination approaches for immune modulation of being pursued significant challenges exist with respect to suboptimal efficacy safety and tolerability experienced by patients scalability and cost of goods to enable broad patient reach.
It is important to note that despite the significant promise of checkpoint inhibition, such as anti PD. One PDL one antibodies there remains a pressing unmet medical need within oncology foreign effective and well tolerated means of <unk>.
Stimulating and activating relevant anti cancer T cells, while sparing the vast majority of cancer irrelevant T cells solution.
Can provide as to these challenges.
We will likely emerge as best in class market leaders defining the paths forward for more effective therapeutics, both as standalone treatment options as well as combination approaches for example, with checkpoint inhibitors.
To that end.
As shown in slide four we believe our immuno stat platform offers a potential breakthrough path forward for cancer immunotherapy.
With data from over 100 cancer patients dosed with immuno stats.
From our IL, two based cue 100 series and namely Thats the.
The experience with cue 101 targeting HBV seven.
In Q1 O two targeting wilms tumor one we can summarize some key distinguishing features bolstering our competitive positioning in this crowded space.
There are four predominant in core features to highlight.
First as noted in this slide we have created a therapeutic index for IL two by selectively targeting tumor specific T cells to the T cell receptor or TCR that provides the highest degree of specificity for the desired T cells relevant to anti tumor immunity.
When we referred to a therapeutic index. This basically refers to the ability to dose patients at a range of doses whereby they experienced demonstrable clinical benefit example, an increase in overall response rate.
And or an increase in median overall survival.
We're also having an accepted tolerability profile for maintaining quality of life.
There have been high profile field approaches attempting to develop IL two therapy for cancers. Notable among these recent failures or peg elated versions of IL, two and not alpha variance of IL two.
There's also been failures in combinations with <unk> Mab with for instance.
Kinase inhibitors, where they may have an O IRR, but a very poor tolerability profile.
Our success with IL two may also be replicated.
For many other cytokines and immune activating receptors, where the generation of a therapeutic index would be up.
Mount importance to maximize efficacy, while preserving patient safety and tolerability.
Second our clinical candidates demonstrate anti tumor efficacy in late stage poor prognosis refractory metastatic cancer patients both as monotherapy and in combination with checkpoint inhibitors, namely <unk> anti PD one antibody.
While much of the maturing efficacy data is from our Q1 O. One trial in HPV positive refractory or metastatic head and neck squamous cell carcinoma patients. We have also begun to observed anti tumor activity with our second clinical candidate Q1 O. Two that is currently in the dose escalation portion of a monotherapy.
Trial in patients suffering from metastatic solid cancers, namely colorectal cancer ovarian pancreatic and gastric cancer.
These WT one over expressing cancers have historically not been responsive to checkpoint inhibitor therapy and have a poor prognosis.
Hence demonstrating disease control and anti tumor activity may represent a breakthrough that can be further expanded with checkpoint inhibition and our other combinations to benefit these patients in need of new therapeutic options Matteo will present and discuss these clinical data in greater detail in a moment.
Third point, we believe that maturing clinical data from the Q1 O. One trial offers opportunities to pursue multiple registrational paths and HBV positive refractory metastatic.
Metastatic head and neck patients.
They prolong survival signal that we've seen in the Q1 O. One monotherapy treatment arm in second line and beyond patients in fact, the majority of the patients are beyond third line.
And the enhanced overall response rate with maturing progression free survival and overall survival in frontline patients treated with cue 101, and standard of care <unk> offer attractive development opportunities in these respective lines of treatment to that end, we have submitted a request for discussions and feedback from the FDA to gain alignment.
And clarity on the next steps towards a registrational trial.
Importantly, Q1 O. One serves as a clinical validation beachhead from which we can expand the application of the cue 100 series across many different cancers, a key strength of our platform is the modularity where in any given tumor antigen can be incorporated to selectively activate the relevant cancer specific.
T cells.
This strategy is also significant regulatory advantages since the core IL two framework, which has been derisked by Q1 O. One remains essentially the same across therapeutic molecules of the cue 100 series and this was clearly demonstrated with the <unk> approval of our second clinical candidate at Q1 O to in essence.
The IND application for 102 was supported by the clinical data from cue 101, as an analogue molecule with the FDA did not require us to perform additional IMD, enabling preclinical toxicology studies and we were allowed to initiate the cue 102 clinical trial at <unk>.
Active dose of one Meg per kg, which is essentially a situation that saved us about a year in dose escalation timelines and the associated costs.
And then she will provide additional details on our focused strategy of expanding our preclinical pipeline with validated immuno stats targeting attractive tumor antigens, such as K Ras involving the <unk> hotspot mutations in other tumor antigens.
As conveyed in this slide we believe we are positioned as a potential leading solution provider realizing the promise of precision immune modulation for superior patient outcomes as such we believe our data places us in a potential position as not only first in class for selective modulation.
Of disease relevant T cells, but also best in class therapeutic platform for immunotherapy.
With that background on the progress and differentiation and competitive positioning I am going to turn the call over to Matteo to review the clinical data, particularly what we just presented at SSE Matteo.
Thanks, Dan Good afternoon to everyone listening in on today's call I am, particularly pleased to provide you with the summary update as the clinical data from the ongoing cue 101 trial continues to demonstrate highly encouraging and robust metrics of clinical benefit or heavily pretreated recurrent metastatic HPV positive head.
Neck cancer patients treated with monotherapy and for newly diagnosed patients with recurrent HPV positive head and neck squamous cell carcinoma treated in combination with timber Lizzie Matt as shown on slide five data from the ongoing clinical trials with cue 101, as monotherapy and in combination with <unk>.
<unk> had provided clinical proof of concept and derisking of our immuno stat platform the.
The latest data generated to date in 2023 continues to support prior observations and further enhances our confidence in Q1 O. One as a potential therapeutic for patients battling HPV positive head and neck cancer.
As previously and consistently stated we believe Q1 hundred one's mechanism of action as evidenced by the ongoing data generated to date provides effective and tolerated dose levels, enabling selective expansion of targeted tumor specific T cells.
Current metastatic HPV positive head and neck cancer is a tough incurable disease.
The data we have observed throughout the monotherapy trial bolsters, our position and enhances our confidence that two one on one is in fact stimulated the targeted cancer specific T cells within these patients, resulting in demonstrable antitumor effect.
More importantly, we continue to observe and evolving pattern of disease control and enhanced survival in the monotherapy trial. We believe this enhanced survival is due to the superior qualitative features a tumor specific T cells, given Q1 hundred one's mechanism of action, especially in the tumor micro environment.
And the recent description of the role of IL, two and generating the sectors for CDA positive T cells.
On this note enrollment in the new adjuvant trial is progressing well and preliminary observations demonstrated expansion of T cell <unk> and increases in natural killer cells within the tumor microenvironment. These findings are consistent with the pharmacodynamic changes observed in the peripheral blood of patients.
With cue 101 as previously reported we believe these observations in addition to the clinical efficacy observed in the second and first line recurrent metastatic setting support a development strategy of moving further upstream into earlier lines of therapy, where a larger number of patients who may benefit.
We believe the selective perturbation of the relevant immune cells results in a durable clinical benefit as seen in Q1 O. One treated patients that had failed prior checkpoint inhibitor treatment.
On slide six durable clinical responses are observed with Q1 O. One monotherapy now with new data demonstrating an unconfirmed partial response in a patient at 24 months after starting therapy.
As shown before patient experienced a durable partial response with an approximate 60% reduction in tumor burden evident at six weeks. After the first two cycles of cue 101, which lasted close to one year on therapy. Importantly, this patient also demonstrated a significant reduction in HBV cell free DNA.
That coincided with the initiation of the partial response and HBV cell free DNA remains undetected, but for the majority of time on treatment patient B, who just completed 24 months of treatment has demonstrated an unconfirmed partial response on their cycle 35 scan, notably this patient has also.
<unk> had complete disappearance of HPV cell free DNA in the blood since week six.
The undetectable HBV cell free DNA, which is an increasingly recognized biomarker of disease activity is suggestive of a pathologic complete response, where cure this patient who we expect to have surgical resection of the lesion for history of pathological analysis.
As shown on slide seven the current Kaplan Meier estimate of median overall survival observed in the 20 patients treated at the recommended phase two dose of four milligrams per kilogram is 28 months.
The observed median overall survival of greater than 20 months in patients treated in the third line and beyond is notable when compared to the historical median overall survival of approximately eight months observed in patients treated in the second line and the checkmate one for one in keynote 40 trials of Nivola, Matt <unk>, Matt.
Respectively, as any experienced oncologists understand the survival with third line treatment is expected to be less.
The disease is further developed and become more unstable.
Evolving data continues to support the premise that treatment with cue 101 demonstrate single agent activity by Durably expanding tumor specific T cells with anti tumor activity, resulting in what appears to be a meaningful increase in survival for patients with advanced recurrent metastatic HPV positive head and neck cancer.
Based upon the strength of this data we plan to meet with FDA to define a registration path for Q1 O. One.
The demonstration of monotherapy activity in these patients bolsters, our belief that we should observe complementary mechanistic effects in combination with <unk> <unk>.
As indicated on slide eight I will now provide an update on the ongoing trial of cue 101 in combination with <unk> in first line recurrent metastatic HPV positive head and neck cancer patients.
<unk> is approved for the treatment of first line patients with recurrent metastatic head and neck cancer tumors with complete positivity scores greater than or equal to 1%, which.
Which is an equal which is a measure of PDL one expression the.
The next slide slide nine shows the current overall response rate of 47% observed at first line patients treated with cue 101, and pamper Lizzie met as presented at the <unk> meeting earlier this month.
Overall response rate of 47% observed in patients with CPA scores greater than or equal to one treated with cue 101 in combination with pepper lithium map to date represents a greater than doubling.
Paired to the historical overall response rate of 19% observed with <unk> monotherapy in the keynote 48 study.
Notably for patients with CPA scores of 1% to 19 and overall response rate of 56% was observed with Q1 O. One in Pampa Lindsay met which represents a greater than tripling of the historical overall response rate of approximately 15% observed with <unk> alone. Furthermore, cue 101 also appears to increase.
The overall response rate in patients with Cps scores greater than 20 with an overall response rate of 38% for Q1, I wanted to <unk> and an overall response rate for 23% for <unk> alone.
In totality, our data suggests that not only does Q1 O. One appear to demonstrably enhance the response rates of anti PD, one inhibition, but also does so by substantially expanding responses in patients that are traditionally less likely to respond.
This is particularly important since patients with low Cps scores range of 1% to 19 represent approximately 50% of all patients that are cps positive and eligible for treatment with checkpoint inhibitor in the frontline setting.
The swimmer plot shown on slide 10 shows that 21 of the 22 patients treated to date at the <unk> and the ongoing combination trial of cue 101 remain alive as of the last follow up for each patient of note. The median progression free survival is still maturing and is currently at five eight months.
Which compares favorably to the historical median progression free survival of $3 two months observed with <unk> monotherapy in the keynote 48 trial.
<unk> patients have live beyond 12 months.
Which was the medium overall survival observed in patients treated with <unk> alone in the keynote <unk> <unk>.
48 study.
A summary of the clinical validation and platform Derisking of immuno stats via the cue 101 clinical experience as shown on slide 11.
Key observations in patients treated with cue 101 monotherapy in the third line and beyond include demonstration of single agent anti tumor efficacy evidenced by resist based partial response.
And durable stable disease in third line and beyond recurrent metastatic cancer patients and a median overall survival of greater than 20 months and the recommended phase II dose cohort.
In the first line study 101 in Pampa Lizardman demonstrates an objective response rate of 47%.
And our current median PFS of close to six months, which is continuing to mature as previously announced the robust data on cue 101 as activity in monotherapy and in combination with <unk> enabled the granting of <unk> fast track designation for the treatment of patients in both the first and third line setting.
The fast track designation will facilitate planned interactions with the FDA has defined a monotherapy registration path.
The cumulative data from these ongoing trials with Q1 O. One have provided us with clear evidence of targeted expansion of HBV <unk> specific T cells with antitumor activity as a single agent and as a complementary mechanism with checkpoint inhibition for what we believe will broaden patient reach and enhanced.
Efficacy of checkpoint blockade therapies.
Furthermore, we believe the preliminary observations from the Neo Adjuvant study in addition to the clinical efficacy observed in the second and first line recurrent metastatic setting supported development strategy of moving further upstream to earlier lines of therapy, where a larger number of patients who may benefit.
As such we believe cue 101, our first biologic therapeutics from our cue 100 series represents a potential therapeutic breakthrough for patients.
Moreover, we believe the data from Q1 O. One has provided a derisking and mechanistic validation for additional biologics from the IL two based Q1 series beginning with cue 102.
As a reminder, shown on slide 12, Q1 O. Two in Q1 O. One shared 99% amino acid sequence identity. This enabled us to significantly decrease the development time and cost of cue 102, as we're not required by the FDA to repeat IND, enabling toxicology studies toxicology studies for Q1 or two and we are also.
We're able to initiate the phase one dose escalation study at one milligram per kilogram dose at which we observed clear signs of biologic biologic activity with cue 101.
As shown on slide 13, we are conducting the Q1 O two dose escalation study in colon gastric pancreatic and ovarian cancers. This design offers us the ability to perform monotherapy expansion studies in any or all of the indications being evaluated in the dose escalation phase.
The trial.
The study is actively enrolling patients in all four indications the patient screening enrollment rate continues to go exceedingly well underscoring investigator enthusiasm and the need for effective therapies and WT one positive cancers, we have observed substantial WT one expression across the target indications with 60.
Percent of colorectal, 53% of gastric, 100% of ovarian and 60% of pancreatic cancers testing positive.
We have completed enrollment of patients in cohort four at a dose of eight milligrams per kilogram and are expanding the two and four milligram cohorts Q1 O. Two has been well tolerated to date with no dose limiting toxicities observed.
The expansion of cohorts, two and three we will provide additional pharmacokinetic pharmacodynamic and antitumor activity data to help inform the selection of the recommended phase two dose for the expansion cohorts.
Data on the first 18 dose escalation patients treated with cue 102 shown on.
Slide 14 demonstrates encouraging disease control with rates of 80% and 75% observed in cohorts two and three respectively. In this heavily pretreated patient population seven of the 11 patients treated in cohorts two and three remained on treatment at the time of data cutoff.
Reductions in tumor burden had been observed in patients treated in the dose escalation portion of the study is shown on slide 15, a patient with gastric cancer that progressed and three prior lines of therapy, including a checkpoint inhibitor has experienced a decrease in the sum of three target lesions that minus 29% at week 12.
Four and continues on treatment.
Reductions of approximately minus 50% in the tumor marker CA and CA 19, nine coincide with the shrinkage of the patient's cancer.
Another example of reduction in tumor burden observed in the two milligram per kilogram dose escalation cohort. This time in a patient with ovarian cancer is shown on slide 16.
This 52 year old patient that progressed four prior lines of therapy has experienced an unconfirmed partial response.
With a reduction of minus 30% in their tumor burden.
We are encouraged by these early observations of monotherapy antitumor activity in these indications where checkpoint inhibitors has been largely ineffective. We look forward to presenting additional data at an upcoming scientific meeting.
I'll now turn the call over to niche a niche.
<unk>.
Thanks will and thank you all for joining this call today as Matteo highlighted the maturing clinical data with cue 101, and one or two bolstered the validation for immuno stats as a differentiated class of T cell engage a therapeutics that can be deployed widely for immunotherapy of cancers.
To that end slide 17 depicts the opportunity for expansion of the cue 100 series to generate therapeutic molecules targeting numerous cancers note that the core IL two components remain the same among all therapeutic candidates with the primary difference being the tumor antigen HLA complex that provides selectivity for the cancer is being <unk>.
Got it.
Following the success with our clinical assets cue 101 in Q1 or two.
We have designed and manufactured a rich pipeline of preclinical immuno stat candidates that can be readily progressed towards the clinic. Examples of some of these preclinical candidates include immuno stats targeting mutated K Ras isoforms, especially the hotspot mutations with variance at the GE 12 position from including <unk> <unk> and <unk>.
D and additional immuno stats targeting well characterized tumor antigens, such as major for prey and cole <unk> III, which is derived from a tumor specific splicing variant of collagen type six out for three protein and appears to be shared across many solid cancers. Many of these preclinical immuno stats have also been validated and functional.
T cell assays. It is important to highlight that the evolving immuno stat pipeline encompasses multiple cancer targets and multiple HLA allele, which together provide broad patient coverage for many cancers. In addition, we've also evolved the platform to accommodate multiple tumor antigens and personalized neo antigens. This.
Potential of our platform is known as Neo stat as shown on the right side of this slide and the Neo stat framework. The peptide binding pocket of the HLA is empty, which which allows us to readily conjugate different tumor epitopes to generate off the shelf therapeutic molecules neo stats are a potential solution for tumor heterogeneity.
And offered an attractive opportunity for personalized cancer immunotherapy.
Taken together, we believe the IL two based cue 100 series can generate an infinite number of therapeutic molecules to address solid and hematological cancers.
Next slide slide 18 highlights the important feature of TCR selective targeting in generation of a therapeutic index for <unk> the cost structure of an immuno stat as shown in the example on the left allows for selective engagement and activation of the tumor specific T cells, while avoiding the systemic activation of all T cells. This print.
People of generation of a therapeutic index, we are focusing on disease specific T cells can be applied to many other relevant demand signals and as noted here our platform is well positioned to exploit the full breadth of the therapeutic potential of other cytokines, such as IL 17, IL 12, IL, 15, et cetera, and cell surface receptors like <unk>.
For one BB among others for immunotherapy of cancers, I will point out that numerous other approaches have tried to harvest. The signals just mentioned for cancer immunotherapy. However, these attempts have been largely unsuccessful due to the lack of a therapeutic index, resulting in poor drug tolerability and suboptimal.
Efficacy, we believe our approach with immuno stats should circumvent many of these challenges as already demonstrated with the IL two based cue 100 series.
Moving on to Slide 19 that describes notable features of superior differentiation that immuno stats offer over the current categories of patent T cell engaging molecule as mentioned earlier by design of immuno stats of Tcs elective engages of only the tumor specific T cells. In contrast, other T cell engages a promiscuous and engage.
Every T cell, we are broadly expressed molecules like <unk> 28, due to the selective <unk> avoid the broad systemic activation of the immune system to minimize toxicities on the other hand, the patent diesel engage molecules have had notable challenges with systemic immune activation and related toxicities, which have been.
Significant hurdles in further in clinical development, the Tolerability and toxicity challenges of patenting cell engages have also hampered combination approaches with other agents, including standard of care therapies, such as checkpoint inhibitors such combinations in patients have often resulted in a significant increase in toxicities.
<unk> fatalities in contrast, the favorable tolerability profile of immuno stats has enabled us to pursue combination therapies in our clinical trials with little to no evidence of a synergistic toxicities as Matteo shared our clinical data with cue 101 in <unk> and frontline recurrent metastatic head and neck cancer patients demonstrates significantly.
Greater efficacy, while not compromising patient safety Q1 O. Two seems to have a similar tolerability profile to cue 101. We're in currently in the monotherapy dose escalation trial, we have completed dosing the highest cohort at eight weeks, but.
With no evidence of dose limiting toxicities, and finally and very importantly in contrast to the generic classes have been T cell engages the clinical derisking of the immuno stat platform offers significant regulatory advantages and clinical development efficiencies as previously described by Matteo. We believe these are significant.
<unk> wins for a first in class therapeutics platform that has convincingly demonstrated clinical efficacy and tolerability.
I'll now change gears slightly and give you a brief update on our platform applications in autoimmune and inflammatory diseases as shown on slide 20, we have developed two broad classes of therapeutics addressing autoimmune disorders for diseases with well described and dominant antigens. We can deploy the cue 300 series of immuno stats for select.
<unk> targeting and down modulation of auto reactive T cells. In this case, we've used the national signal of PD ligand, which we know is involved in maintaining peripheral tolerance, we have demonstrated feasibility and proof of concept in type one diabetes. We are selective dampening of pro insulin specific T cells. Another extension of this approach.
Can be used for selective depletion of Autoreactive pathogenic T cells, while sparing protective immunity. We are currently engaged in discussions with prospective partners to progress our work in antigen specific targeting of Autoreactive T cells.
Our other program in Autoimmunity is Q4 to one which is an all of the TGF beta IL two by specific for selective induction in expansion of regulatory T cells or T. Rex, which are a key cellular component of maintaining immune balance by controlling and suppressing pathogenic inflammatory responses. This program has.
Been a very productive collaboration with Ono pharmaceuticals, what in <unk>.
<unk> is supporting all of our ongoing preclinical work to identify and optimize clinical lead compound Q4 hundred one offers a unique opportunity to not only expand the preexisting regulatory T cells, but also position possesses the ability to convert naive CD four T cells into T regs, thereby enhancing the quantitative and qualitative.
Great a fraction of T. Regs early data from this program has demonstrated potent activity in in vitro assays as well as generation of stable T. Reg cells and early in vivo studies have demonstrated efficacy in an animal model of gastritis as shown on the right side of this slide this is a disease model developed by Dr. Richard Depaolo.
St. Louis University.
A short treatment with Q4 to one resulted in a long lasting protection from gastritis as demonstrated by the pathology scores shown here.
Our teams are working diligently with our new colleagues to aggressively advance the Q4 hundred one program in order to enable the next stages towards IND filing we will provide more updates in the future as the current ongoing studies generate mature dataset with that background on the platform applications in oncology and autoimmunity I will now pass the call.
To carry to review the financial details following Gary's remarks, Dan will provide some additional context on our strategic positioning and continued next steps of our corporate development Terry.
Turning to slide 21, I'd like to provide an update on our financial results for the three months ended September 32023.
During the third quarter.
We reported collaboration revenue of approximately $2 1 million as compared to 68000 for the same period in 2022.
Revenue in the third quarter was primarily due to work related to our collaboration with Ono Pharmaceuticals.
For Q4 hundred line, which means just described research and development expenses were $9 9 million and $7 6 million for the three months ended September 32023, and 2022, respectively.
The increase was due to higher clinical expenses stock based compensation and research and laboratory expenses in the third quarter.
General and administrative expenses remained steady at $3 6 million and $3 5 million for the three months ended September 32023, and 2022, respectively.
As of September 32023, the company had approximately $54 7 million in cash and cash equivalents $40 3 million and working capital and 40 $45 1 million common shares outstanding we expect our current cash and cash equivalents to fund operations through 2024.
I'll now turn the call back over to Dan for closing remarks, Dan.
Yes, Thanks Carey.
As conveyed at Citi last weekend and now summarized on this call. The design of our immuno stat molecules achieves selective modulation of disease relevant T cells, while sparing the detrimental effects of the stimulation of the vast majority of irrelevant T cells in essence, we believe we have a.
Chief the biologic equivalents of precision targeting, thereby creating a therapeutic window for potent cytokines such as IL two.
This desired profile enables combinations with for instance, checkpoint inhibitors, where in the complementary mechanism of actions should provide enhanced efficacy, while not compromising tolerability and patient safety as shown on slide 22, with our clinical data from cue 101, plus <unk> in front.
Why in HPV positive refractory or metastatic head and neck cancer patients.
Turning now to slide 23, let's review.
The modest overall response rates reported.
On checkpoint inhibitor monotherapy in various solid tumor cancer types.
It's important to note that while checkpoint inhibitors opened up the potential promise of immuno oncology their impact on anti tumor efficacy is primarily dependent upon the presence of a robust anti tumor T cell repertoire.
As such the rational combination of checkpoint inhibitors in immuno stats increases the probability for patients to derive enhanced therapeutic benefit from immunotherapy.
And that's actually shown if you look at the head and neck cancer patient, we increased the overall response rate from 19% with <unk> alone.
Frontline, 247% in the combination.
Okay. Finally.
Let's move to slide 24 shows the anticipated milestones and accomplishments we anticipate achieving.
Over the next year, including the defined prospective registration path for cue 101, as well as multiple clinical milestones with our two clinical candidates in several solid tumor types.
It is important to note that we have.
We're very well positioned for strategic alignment with prospective partners, recognizing the potentially disruptive implications of our emerging data.
We look forward to continuing our progress forward into a highly productive and transformative 2024 with that I'm going to turn the call back over to the operator, and we will now open the call open to questions.
Operator, thank you ladies.
Thank you, ladies and gentlemen, we will now conduct the question and answer session.
If you have a question. Please press star followed by the number one on your touch pad.
If you wish to cancel your request please press star two.
Please ensure to lift your handset if you're using a speaker phone before pressing into geeks.
Your first question comes from Stephen Willey from Stifel.
Your line is now open.
Hi, guys. This is Mike.
Can you guys hear me okay.
Yes. Thank you.
Thank you. Thank you for taking my questions and congrats on the data.
I have just two quick one on my end. So the first one is starting with Q1 O. One I understand that you guys have made a request to FDA and it looks like you are now planning on defining a registration path in the beginning of 2024 and I'm wondering what the format of that communication.
Can be would it be just the press release or do you think you will likely disclose that information during earnings call et cetera.
Second as it relates to Q1 of two and very interesting data and.
I guess my question would be what gives you guys the confidence and.
Pursuing colorectal and pancreatic cancers and expansion cohort this site.
Hi.
Q1, <unk> come with time that will be it. Thank you very much.
Okay. The first question.
I want to emphasize that these.
The request for discussions with the FDA are basically our initial discussions regarding.
Registrational trial design and the first foray is in the second line and beyond monotherapy, but we view this as a really important sort of foundational discussion to build support for our subsequent dialogue with the FDA for <unk>.
Defining future Registrational pads et cetera, I also want to emphasize we are in the we are engaged in some partnering discussions and we want to be cognizant of the fact that.
Defining registrational trials.
To correspond with those partnering objectives as well. So this is an important initial interaction with the FDA to establish kind of foundational support for the mechanism of 101 as a monotherapy, which then builds on our subsequent discussion. So that's really the strategy there.
With 102.
Again, we have done a basket study in the dose escalation.
Initially we were looking at focusing on colorectal, but based on the observations were seeing where were looking at several tumor types that we would likely do a patient expansion in <unk>.
I'm going to turn this over to Matteo if he wants to elaborate on that.
Yeah, Thanks, Dan just to add a couple of points.
We're very.
We're happy with the Tolerability profile that we've observed to date in.
In addition to the signs of antitumor activity in multiple indications and so just to sort of set the context for this late line of colorectal cancer.
These patients are very advanced very refractory.
And if you actually look back to the approval of <unk>.
In colorectal patients.
There was about a 30% disease control rate at six weeks that ultimately was then associated with the 1.4 month increase in survival and that led to the approval of that drug in late late late line colorectal cancers. So so observing stable disease.
And a high proportion of patients.
Even that six weeks is significant.
And then Furthermore, we have patients now across several indications with stable disease beyond 18 weeks and that includes patients with pancreatic cancer.
And then as we've shown the patient with gastric cancer that has a very close to the threshold partial response at 24 weeks continues on therapy. So so we're very encouraged as our investigators bye.
By our observations.
And in fact, our investigators are really keenly interested in pursuing all of the indications.
And we going forward, we'll consider how doing so and the timing of that fits in our overall development strategy for cue 102.
Very helpful. Thank you.
Your next question comes from Ren Benjamin from JMP Securities. Your line is now open.
Hey, guys. Thanks for taking the questions and congratulations on all the <unk>.
All the data that was released its nice to see the continued improvement in overall survival several questions from us.
Maybe just starting off with the cue 101 series when we talked about.
That patient who got a PR.
Quite late.
And the whole process can you talk a little bit about <unk>.
How many doses that patients.
Actually receive to they continue to receive doses or has the dosing schedule been modified at all.
And then sticking with cue 101.
The combination study if we focus just on the LOE Cps patients can you talk a little bit.
About the duration of response and maybe the the PFS as well for those patients.
Yes, Matteo you want to take that.
Sure so.
Thank you for the question.
Regarding the patients that had stable disease for 24 months.
This is again the patient that at six weeks had undetectable cell free DNA. So you asked regarding the length of their treatment. It was a complete 24 months. This patient did have their regimen reduced from Q3 to Q six weeks after approximately 12 months or 14 <unk>.
<unk> a treatment, but they completed the whole two years of therapy.
Im sorry now the second question was what was.
In terms of now.
Durability, low cps patients and the duration progression free survival.
Thanks.
Yes.
Yes, so the.
The durability really is it's evolving so so it's maturing so we have several patients with ongoing objective responses. So it's really a bit premature.
Thank to define the duration of response.
It's approximately 30 weeks now, but really maturing with several patients remaining on treatment.
Median PFS is close to six months.
And again that compares favorably to the monotherapy data wherever it is approximately three months from keynote 48.
But again as the duration of response needs time to further mature.
The PFS will be maturing as well in parallel.
Got it and then just.
You had mentioned you had made some comments material in the call regarding the neo adjuvant trial.
I was wondering if you could provide a little bit additional.
Additional color on those observations.
Maybe maybe.
Anything you can provide as it is it just TD eight in CD four T cells that are that are moving up or are there.
<unk> involved as well.
Kind of what are next steps and when might we see that that.
That data.
Certainly so so this is really an exciting trial and a wonderful opportunity to look at the effects of Q1 O. One on the tumor microenvironment.
In a setting where one can obtain substantial amounts of tissue from biopsy.
And so again just to point out that this is an investigator sponsored trial at Washington University.
However, we have.
<unk> been able to see some preliminary data, which is really very very encouraging.
And what we've seen is expansion of T cell <unk>.
In the tumor microenvironment and increases in natural killer cells in the tumor microenvironment after two doses of cue 101.
The study continues to enroll I think we anticipate enrollment may be complete.
By the end of next year.
And we are respectful of the investigators desire.
Publish this work.
The time is right.
But it really certainly is very supportive of everything we've observed to date in <unk>.
Our clinical study.
Got it I'll ask one more and then just hop back in the queue as we think about <unk> Q1.
And that program and the advancement of that program.
I kind of look at Q cue 101 is kind of the poster child. So.
The question what potential combinations might you.
Ultimately want to be exploring.
As you move that program forward.
Yeah. So great great question. Thank you.
I think clearly.
As we learn more about the activity of cue 102 in the different <unk>.
Tumor types.
The rational next step with regards to development would be to look at combinations.
And potential combinations, I think will likely depend on which tumor type one is talking about and so we looked for example at gastric cancer, where we've seen this tumor reduction of 24 weeks duration.
But considering a combination with the anti PD, one or checkpoint inhibitor given the history of some although limited activity in some subsets of gastric cancer.
I think in other <unk>.
Indications like colorectal cancer, it would be very interesting to move up one or two lines of therapy.
I'd think of combinations, perhaps even with chemotherapy or anti VEGF therapy. For example, but this is certainly.
An area of very active deliberation for us.
And it of course, dovetails importantly, with our strategic.
Ongoing activities with potential partners.
Great. Thanks for taking the questions and I'll hop back in the queue.
Okay. Thanks Brent.
Okay.
Your next question comes from.
Tim Hoff from Piper Sandler.
Your line is now open.
Great. Thank you very much.
I appreciate it all of it.
The update.
Just kind of looking at now that you've really got immuno stat proof of concept.
One other or some of the year.
You've talked about <unk> in the past.
No word potential partners be interested in looking at their own antigens on this active construct.
Or are they more.
Looking at kind of the existing products or maybe even kind of a mixture of both thank you.
Yes.
And that over to a niche thanks.
Hi, Ted and thanks for the question so Ted as you well saw with some of what we've said in the expansion.
Going after primary cancer drivers is obviously, a low hanging fruit so mutated K Ras.
As you are aware of the GE 12, see small molecule covalent inhibitor for <unk> being approved in the Amgen call bonds. We believe the valeant in the aspartic acid well appreciated a much larger patient populations, particularly in the three major cancers of colorectal lung and pancreatic so.
They do donate T cell epitope, so just in that space for example.
We've got four different <unk> molecules addressing <unk> D on a couple of different HLA and Niels <unk>.
We've also closed strategies looking at other primary mutated cancer drivers and that is still early in the pipeline, but we have confidence they'll be validated.
Got primary tumor drivers like MAGE, a four and a cancer testis antigen that offer very attractive opportunities and perhaps some level of validation through the ongoing work of others looking at TCR T cell therapy approach is of course positive with a biologic so very different application and perhaps a bit more.
Easy to sort of think about from the commercial and patient.
Accessibility viewpoint.
We've got interest on these sets of antigens from certain set of policies to what you referred to going after some of these primary drivers, but then as you well know there is a significant community out there that has been focused on discovering and doing their own work would be spoke antigens, which the platform can easily be deployed to drug those more.
To that end Neo stat becomes a fantastic opportunity and that's one of the reasons, we sort of highlighted that even though that is an extension of the immuno stat of the opportunity. There is the fact that you can go after multiple antigens that and it's the same quartile two framework. So we do believe the efficiencies and the advantages that we have.
Demonstrated 101 in one or two should apply to neo stat as well. So there is again, we look at this in three broad buckets, we look at drive around regions, where single dominant I'm goods should have benefited 101 is a great example, because <unk> is a viable portable oncogene in the case of HPV driven cancers and by the way that data is in head and neck cancer. That's a molecule can go.
Two other indications like cervical penile anal vulvar cancers, as well one or two with what Matteo just described follows up a beautiful example of Oncall fetal antigen that is selectively expressed in has activity and then K Ras for obvious reasons, including the major foreign frame followed suit and then we've got this opportunity to go after.
People different outages, but one can simply deploy the platform and Thats. The reason I highlighted the plug and play approach virtually hasnt limitless potential to generate therapeutics.
That's super helpful really exciting time for the company.
Thank you thank you Ted.
Your next question comes from Ren Benjamin from JMP Securities. Your line is now open.
Hey, guys. Thanks for taking the follow up.
You mentioned on the call.
Partners and partnerships and I guess I'd like to just if you can provide a little bit additional color as to maybe how those.
The discussions are going should we be thinking about.
I don't know sort of the who's who of.
Checkpoint.
Inhibitors, or who you are kind of talking to or are there other types of <unk>.
Potential partners for 101 right.
That you're talking with and I guess, just as a follow up to that does a partnership.
Is that necessary to move into.
Our pivotal study.
Or is that something that you bill.
Believe after the FDA discussion is complete.
You might need to and want to take on your own thanks very much.
Yes.
You're welcome.
Important question Ren and it's a complex question, but it doesn't have a simple answer.
So let's start off with the last part of the question.
It's not necessary for going forward with a pivotal study, but I would say with the current market dynamics that the biotech sector, particularly oncology is confronted with the headwinds in the capital markets. We have limited resources and we're trying to.
Look at dynamically how do we continue to evolve the platform for maximizing patient reach and.
And demonstrating the value of our platform for addressing.
Serious disease cancer autoimmune et cetera.
So we're looking at partnering strategies that.
Give us flexibility.
Still engaged in involvement in the drugs development, we don't want to become a licensing company, we want to become a strategic collaboration partner.
And I would say <unk> is a great example, we have a co development option.
With that in that collaboration.
In terms of the characterization of the companies we're talking to what's the full spectrum was certainly talking to the who's who I'd say, what's intriguing is first of all we very deliberately did not go out with a BD emphasis early on in our development. We wanted to build a sound substantive data package.
Based on rigor and solid data that we could stand on.
We're also getting sort of inbound inquiries and that's actually very encouraging so we're talking to a spectrum of potential partners.
And I would say sort of spectrum of opportunities and different sort of structures that we're assessing so I appreciate.
The question I can't answer it with any more detail for obvious reasons, but.
Doing the best I can to address.
The address your question.
Yes, Thanks, I appreciate that and good luck going forward.
Thank you.
Ladies and gentlemen, as a reminder, should you have any question. Please press star followed by the number one.
Okay.
Yeah.
There are no further questions at this time than <unk>. Please proceed with your closing remarks.
Okay, great. Thank you.
First we want to thank those of you listening in to this call.
Recognizing the importance of our mission towards developing these important novel therapeutics for enhancing patient treatment outcomes for debilitating disease.
We want to thank our employees for their consummate dedication and professionalism, helping us achieve our mission.
And obviously, we want to thank our shareholders and board of directors for their support most importantly, we want to thank the patients and their families participating in these ongoing and important trials. So thank you again for listening and take care. Thank you.
Ladies and gentlemen, this concludes today's conference call.
Thank you for joining you may now disconnect.