Q2 2023 Cue Biopharma Inc Earnings Call
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Greetings and welcome to the cue Biopharma Investor update call at this time, all participants are in a listen only mode.
A question and answer session will follow the presentation.
Anyone should require operator assistance during the conference. Please press star zero on your telephone keypad as a reminder, this conference is being recorded.
I would now like to turn the conference over to Dan for theory cue Biopharma as Chief Executive Officer. Thank you you may begin.
Alright, Thank you very much 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 please be aware that the slides accompanying today's update may be advanced directly by those listening in on the call and will be notifying you as we proceed through the presentation.
Joining me on today's call is Dr niche theory.
Our president and Chief Scientific Officer, Dr. Matteo <unk>, our Chief Medical Officer, and Carrie Carrie Ann Miller, our financial Chief Financial Officer as shown on slide number two.
This presentation may.
It may contain some forward looking statements any forward looking statements made during this call represents the company's views only as of today August nine 2023.
On the next slide which is slide number three just outline the agenda for today's call I'll begin with a brief summary, followed by a niche a niche will provide you with some background context pertaining to our approach and resulting developments regarding the immuno stat platform with a brief synopsis of associated competitive advantages pertaining to.
The observations from our ongoing clinical trials following the background provided by our niche Matteo will then provide an update on observations from our ongoing clinical development regarding mechanistic insights have any corporate development implications for our ongoing corporate strategic positioning.
Both the nation Matteo during the presentation, we'll providing updates with some of the data and slides haven't been previously presented and discussed on prior calls are the repeat of that data is meant to provide contacts and continuity in our foundational premise, but also serves to reinforce the consistent and steady progress forward demonstrating.
The realization of our foundational vision to enable precision immunotherapy.
Helping to transform the treatment of cancer.
Following Matteo a niche will return with a brief overview of our preclinical pipeline developments and then that'll be followed by Kerry who will provide an overview of our financials for Q2 and going forward and going forward guidance. I'll, then return for concluding remarks, and we'll open the call up for questions I'm now going to turn the call over to a niche a niche.
Thanks, Dan.
As noted in slide four the foundational premise envisioned for our therapeutic platform has centered on harnessing the naturals signals or nature of Skus that the immune system utilizes to guide its effector functions, including recognition and destruction of malignant tumor cells. We believe this approach provides us with a significant advantage by exploiting with evolution.
<unk> has already refined which is a herculean task of creating molecules and signaling pathways that lead to balanced immune responses.
Most importantly, these signals on nature of Skus have been fine tune and optimize to provide protective immunity, while preserving the safety of the host used.
Using these underlying principles of selectivity, we have engineered and now clinically validated new class a bi specific T cell engages termed immuno stats for the selective modulation of disease relevant T cells, while sparing the broad nonspecific immune activation.
Or carpet bombing of the entire immune system.
For oncology applications, we've been able to de lever natural immune activation signals such as the cytokine IL two selectively to the tumor specific T cells. This property enables us to create a meaningful therapeutic index to exploit the promise and potential of targeted immune activation in the patient the same principle.
Can be applied to any other cytokine or immune modulation signals to the last point, we have published several key papers in top tier journals, demonstrating the modularity and breath of our platform as Matteo will discuss in detail. Shortly we now have exciting insights from recent clinical data that we believe provide very strong support.
And validation for our biologics platform further we believe that these data have positioned us to exploit the breadth of our platform modularity to address patient needs in many cancers and I will comment more on this as we discuss our pipeline and potential for expansion into indications with significant market potential.
Okay. The next slide slide five provides a conceptual framework for maximizing the success of cancer Immunotherapies.
Deploying immuno stats, we have the potential to solve a significant and fundamental challenge, which is a selective activation of their ramp up relation of T cells that express T cell receptors or TCR specific for tumor antigens.
In contrast, many of the current standard of care therapies utilize a blunt sledgehammer approach to activating the immune system with little to no consideration pertaining to the specificity of the T cells being activated.
These approaches as now evidenced by extensive clinical data from modalities, such as bi specifics checkpoint inhibitors or on targeted cytokines result in suboptimal efficacy along with toxicities. We believe our approach not only demonstrates greater efficacy over standard of care, but more importantly appears to achieve.
These outcomes without compromising patient safety.
Slide six provides additional details into the design and functional attributes of our lead clinical candidates that are derived from the IL two based cue 100 series.
As noted here immuno stats are selective engages of TCR of tumor specific T cells and deliver functional IL two signals to dose very T cells. The cue 100 series architecture is composed of two natural signals one of the stabilized peptide HLA complex or PHA that selectively engage select.
<unk> binds to only the tumor specific T cells note that the specificity is driven by the T cell epitope shown in yellow that is a tumor specific peptide sequence. The other natural signal is an affinity tuned IL two molecule that cooperates with TCR signals to fully activate T cells into potent killers of tumors.
This functional cooperation of concurrent TCR signals and IL two signals is bespoke to nature selective design and hence results an exquisite specificity.
The generation of a therapeutic index for the right tumor specific T cell over all other irrelevant T cells is further supported mechanistically by the elegant lifestyle microscopy experiments conducted by Dr. Michael <unk> lab at University of Oxford.
Dr. <unk> is a member of the National Academy of Science and is a pioneer in describing the molecular details of T cell activation.
As shown here the engagement of the immuno stat with the antigen specific T cells that is the T cell bearing the right T cell receptor, resulting formation of an immune synapse and TCR clustering and activation as shown in green when the same immuno stat engages and irrelevant T cell no such effect as noted.
Before I pass the Golden Matteo summarize our key highlights and accomplishments as shown on slide seven to note. We have developed a novel first in class biologics platform and have treated over 80 patients thus far with evidence of anti tumor efficacy and Tolerability importantly, we've had patients in our trials that have continued to receive drug for up to two years.
Underscoring the durability of the clinical activity and Tolerability profile.
We have demonstrated monotherapy activity in late stage head and neck cancer patients that have failed several lines of prior standard of care therapies, including checkpoint inhibitors Matteo will elaborate on the significant survival signal we are observing in our monotherapy patients in the frontline setting where anti PD. One therapies approved we have combined our immuno stat stood.
Demonstrated greater than doubling of the overall response rate. The overall survival data for these patients is continuing to mature importantly in patients with low Cps scores, which reflects the level of PD ligand expression in the tumor.
We have seen an even greater increase in response rate over anti PD, one therapy alone. It is well recognized that patients with low Cps scores constitute a significant population and a notably less responsive to checkpoint inhibitor therapy.
One possible explanation for the significant increase in responses and Cps locations may pertained to the observation that immuno stats increased the targeted T cell population and also engage T cells in the tumor tissue, which may alter the tumor microenvironment to be more permissive to immune attack against the cancer.
Looking forward Q1 on ones maturing clinical profile in both the monotherapy and combination trials.
Provides us with a range of potential long term development and strategic strategic opportunities. We also believe that the clinical data with Q1 O. One have validated a de risked a broader platform to that to that end. The FDA acknowledged that the clinical and safety data from Q1 O. One provided sufficient confidence to allow the acceptance of our second IND with cue 102.
Without the need for additional IND, enabling toxicology studies and allowed us to start the Q1 or two monotherapy dose escalation at the clinically active dose of one make vacate the latter point shorten our dose escalation in patients significantly and saved us approximately a year in clinical development timelines, we believe this year.
<unk> regulatory advantages are a significant accomplishment and differentiating feature for our biologics platform from a platform modularity perspective, the core IL two framework remains conserved between different cue 100 series immuno stats. The primary difference is at the level of the tumor antigen specificity or the <unk> part.
For example, Q1 O one in Q1 or two or 99% sequence identical except for the tumor antigen T cell epitope and is providing a very modular framework.
Development of distinct therapeutic molecules against a wide range of cancers.
Lastly from a manufacture ability and cost of goods perspective, immuno stats are manufactured using established in conventional CMC protocols for monoclonal antibodies and FC fusion proteins.
Yields are similar to monoclonal antibodies in grams per liter and GMP stability has been impressive for example, cue 101 has a shelf life that goes north of three years, which is comparable to or better than most monoclonal antibodies.
That's an option I will now pass the call to Matteo to provide the most recent clinical update for Q1 O. One in Q1 or two.
Yeah.
Thanks, and H the clinical data from the ongoing cue 101 trial continues to demonstrate highly encouraging and a robust metrics of clinical benefit for heavily pretreated recurrent metastatic HPV positive head and neck cancer patients treated with monotherapy and for newly diagnosed patients with recurrent metastatic HPV positive.
They've had neck cancer treated in combination with pampered Lindsay map.
As shown on slide eight data from the ongoing clinical trials with Q1 on one as monotherapy and in combination with <unk> lithium map have provided clinical proof of concept and derisking of our immuno stat platform. The latest data generated to date in 2023 continues to support prior observations in further.
<unk>, our confidence in cue 101, 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 directly in the patient's body.
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 Q1 and one is in fact stimulating the targeted cancer specific T cells within these patients, resulting in demonstrable antitumor effect.
Furthermore, and 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 persistent expansion of tumor specific T cells, given Q1 hundred one's mechanism of action, especially in the tumor microenvironment.
As shown on previous webcast I'd like to review the data on slide nine.
It is very important to understand the mechanistic differentiating features of Q1 O one including its effects on NK cells and tumor specific T cells in the blood and the tumor microenvironment and clinical trials to date cue 101 demonstrates well behaved and consistent pharmacokinetics with low inter patient variability at the RPT.
<unk> four milligrams per kilogram.
Closure pattern is consistent throughout multiple cycles of treatment without any attenuation of PK parameters supporting the premise that there is no <unk>.
Evidence of clinically relevant immunogenicity.
Regarding its pharmacodynamic or PD profile Q1 O. Two treatment also results in a consistently observed sustained increase in natural killer cells or NK cells are positive attributes associated with an antitumor response as NK cells are known to induce potent tumor killing.
Accordingly.
Yeah.
We have also consistently observed only a slight and transient increase in regulatory T cells regarding the intended PD effect I E. The activation of targeted tumor specific T cells. We have observed as shown in the middle panel 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.
<unk> and post treatment biopsies demonstrate an increase in tumor infiltrating T cells and associated tumor necrosis. We believe this invasion of T cells into the tumor transforms the tumor microenvironment and plays a key role in the clinical activity observed with cue 101, monotherapy as well as that observed when.
Buying with a checkpoint inhibitor in.
In addition to the favorable PK and PD just described in patients with advanced HPV positive head and neck cancer. We're also observing a spectrum of patterns of clinical benefit in patients that have failed prior checkpoint inhibitor treatment as we have shown before and now on slide 10, various patterns of clinical efficacy observed with Q1 O one monotherapy.
As shown on the last patient experienced a durable partial response with an approximate 60% reduction in tumor burden evidenced 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 coincide with the initiation of the partial response and HBV cell free DNA remains undetected bulk or the majority of time on treatment patient B, who just completed 24 months of treatment has had durable stable disease with tumor burden.
<unk> of approximately 20% observed at week 48, and maintained the present time, notably this patient has also had complete disappearance of HBV cell free DNA in the blood since week six.
Undetectable HBV cell free DNA, which is an increasingly recognized biomarker of disease activity and suggestive of a pathologic complete response E. A potential cure and this patient who we expect may at some point have a surgical resection of the lesion for hyster pathological analysis patient.
His experience tumor reduction after a prolonged period on drug where no resist based objective response was initially observed by imaging.
After approximately six months on treatment the tumor begin to shrink and the patient remained on therapy for greater than 18 months after starting treatment with cue 101.
As shown on slide 11, the current median overall survival observed in the 20 patients treated at the recommended phase two dose of four milligrams per kilogram is approximately 14 months.
<unk> median overall survival of 14 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 trials.
In the second line Checkmate 141, and keynote 40 trials of Nivola map and pamper lithium mab respectively.
Any experienced oncologists understand the survival with third line treatment is expected to be less as the disease is further developed and becomes 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 antitumor 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 cue 101.
As indicated on slide 12.
I will now provide an update on the ongoing trial of cue 101 in combination with Pampa lithium map and first line patients with recurrent metastatic head and neck cancer.
<unk> is approved for the treatment of first line patients with recurrent metastatic head and neck cancer that have tumors with TPS scores greater than or equal to 1% Cps is a measure of PD lone expression in the tumor as shown on slide 13, the distribution of PD lone expression observed in.
The key note 48 study population shows that approximately 50% of Cps positive patients have GPS values of one tonight and the other 50% have cps values greater than 20.
Subgroup analysis of the key note 48 study has shown that patients with Cps at 1% to 19 at lower overall response rates lower median progression free survival and lower overall survival compared to the patients with Cps greater than 20, when treated with <unk> lithium mab alone.
As such there is a clear need to expand the therapeutic reach for low cts patients and to improve outcomes for all patients treated with checkpoint inhibitors.
The next slide Slide 14 shows the current overall response rate of 44% observed in first line patients treated with the cue 101 in Pentagon Lizzie map as discussed on the June 14th earnings call since that call. We have observed two additional patients with confirmed responses as shown on the waterfall plot on this slide.
The patient with the prior unconfirmed.
Complete response has had a subsequent scan confirming the complete response, which I will describe in detail momentarily. In addition to the confirmed complete response six of the first 16 evaluable patients treated at the <unk> of Q1 on one and pamper lithium Matt have experienced partial responses now with all six.
Confirmed partial response as defined as a reduction of tumor burden.
Greater than 30% or 30% or greater and additional two patients that have experienced greater than 20% reductions in some of target lesions remain on treatment.
Confirmed overall response rate.
44% observed in patients with Cps greater than or equal to one treated with cue 101 in combination with <unk> to date compares favorably to the historical response rate of 19% observed with <unk> monotherapy in the keynote 48 study.
Notably four out of eight or 50% of the combination patients with low PDL, one expression E. Cps scores of 1% to 19 experienced objective responses, which is greater than the expected rate of approximately 14% with <unk> alone.
As such Q1 O. One appears to significantly enhance the response rate of anti PD <unk> PD, one inhibition, particularly in patients that have PD lone expression, which represents approximately half of the patients eligible for treatment with a checkpoint inhibitor in the frontline settings.
The next slide Slide 15 shows the overall response rates observed in subgroups of patients treated with <unk> alone. According to Cps values in the keynote 48 trial compared to the overall response rates observed with cue 101, and <unk> combination therapy as shown Pam Elysium have.
Straights lower efficacy in tumors with low Cps scores, specifically and overall response rate of approximately 14% was observed with CPA scores of 1% to 19 compared to an overall response rate of 23% that was observed with Cps score of greater than 20 in the keynote 48 study.
For all patients with Cps scores greater than or equal to one.
And overall response rate of 44% was observed with cue 101 in fiber laser met which represents a greater than doubling of the historical response rate of 19% observed with <unk> alone.
Notably for.
For patients with Cps scores of 1% to 19.
And overall response rate of 50% was observed with Q1 at one <unk>, which represents a greater than tripling of the historical response rate of 14% observed with <unk> alone.
Furthermore, cue 101 also appears to increase the response rate in patients with Cps scores greater than 20 with an overall response rate of 38% for Q1 O. One in Pampa <unk> map and a response rate of 23% for <unk> alone.
In totality, our data suggests that not only just Q1 it wouldn't appear to demonstrably enhance the response rate of PD, one inhibition, but also that it does so by substantially enhancing responses in patients that are traditionally less likely to respond.
This is particularly important since patients with low Cps scores, 1% to 19 represent approximately 50% of all patients that are eligible to receive timber Elizabeth.
Additional data on the patient with the now confirmed CR shown on slide 16 demonstrates the time course of response in both target and non target lesions evidenced continue clinical improvement.
A patient had a target disease burden of approximately eight centimeters comprising a lesion at the base of the tongue and to lift nodes and non target disease in the bone liver and lymph nodes partial response was observed at the first scan at six weeks and a complete response was observed in the Tulsa lesion at 18 weeks at week 42.
A complete response was observed in all target lesions, followed by a complete response and all.
In all radiologic evidence of disease at 48 weeks. The complete response was confirmed on scans performed at week 54.
Two of the target lesions, where lyft nodes and they have reduced in size to less tend to less than 10 millimeters I E. The size of a normal lymph node, which in addition to the other findings meet resist criteria for a complete response.
The swimmer plot shown on slide 17 shows that 16 of the 17 patients treated to date at the recommended phase two dose in the ongoing combination trial of cue 101 remain alive and then the last follow up for each patient as an update we just recently treated the 18th patient at the recommended phase two dose and have for <unk>.
Additional patients in screening.
Of note nine patients remain on treatment and to date five patients have lent beyond 12 months, which was the median overall survival observed in patients treated with <unk> alone in the keynote 48 study. The swimmer plot also shows an emerging trend of extension of progression free survival in patients treated at the recommended phase two dose.
60, <unk> hundred one and Pamper Lizzie Matt.
The follow up data on these first 18 patients as well as new emerging data on additional patients treated with combination therapy continues to strengthen and we look forward to providing an update on the cumulative data at the November meeting of the society for immunotherapy of cancer also known as CFC.
Key observations in patients treated with cue 101 monotherapy in the third line and beyond include as detailed on slide 18 demonstration of single agent antitumor efficacy evidenced by resist space partial responses in durable stable disease in third line and beyond recurrent metastatic head and neck cancer patients and a median overall.
Survival benefit.
From survival follow up in the recommended phase II dose cohort.
As previously announced the robust data on <unk> hundred one's activity in monotherapy and in combination with pepper listen that enabled the granting of fast track designation for the treatment of patients in both the first and third line settings. The fast track designation will facilitate planned interactions with the FDA to define a monotherapy registration path the Cuba.
<unk> data from these ongoing trials with cue 101 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.
<unk> therapy.
As such we believe cue 101, our first biologic therapeutic from our cue 100 series represents a potential therapeutic breakthrough for patients. Furthermore, we believe the data from Q1 O. One has provided a derisking and mechanistic validation for additional biologics.
From the IL two based cue 100 series, beginning with Q1 of two.
As a reminder, shown on slide 19, Q1 hundred two in Q1 O. One shared 99% of 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 I'd, enabling toxicology studies for cue 102, and we were also able to initiate the.
Phase one dose escalation study at one milligram, one milligram per kilogram dose at which we observed clear signs of biologic activity with cue 101.
We are conducting the Q1 of 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 of the trial findings.
Findings observed to date are summarized on slide 20. The study is actively enrolling patients and 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 expressing cancers. We are currently enrolling patients at eight milligrams.
<unk> per kilogram and expanding the two four milligram per kilogram cohorts.
102 has been well tolerated to date with no dose limiting toxicities observed evidence of antitumor activity has already been observed in heavily pretreated patients, including reductions in target lesions stable disease and reductions in tumor markers and several patients for example, a patient with gastric cancer that progressed and three <unk>.
All lines of therapy, including a checkpoint inhibitor has experienced a decrease in the sum of three target lesions of approximately minus 25%.
On scans at weeks 612, and 18 and the patient currently continues on treatment.
These early signs of clinical activity are particularly encouraging as they were observed at the one milligram per kilogram in two milligram per kilogram dose levels.
With the scans on the patients dosed at four milligrams and eight milligrams per kilo per kilogram are currently pending.
We are encouraged by these early observations that monotherapy antitumor activity in these indications where checkpoint inhibitors have largely been ineffective.
We look forward to presenting additional data at the <unk> meeting in November .
I will now turn the call over to a niche a niche.
Thanks Matteo.
<unk> Bye Matteo the clinical validation data with cue 101, and one or two provides us enormous confidence to exploit the breadth of our platform to cover many cancers.
Shown on slide 21, the court to framework for each distinct immuno stat remains constant the primary difference between each molecule is the T cell targeting moiety, which is unique to the Kansas specificity in other words. These different immuno stats are essentially analogs of each other to that end, we believe that the clinical experience.
With our first clinical candidate cue 101 provides platform validation and platform de risking we believe this unique positioning has a read through for the entire class of therapeutic molecules that can be developed using our technology platform, which provides a significant competitive advantage.
Core advantage around platform modularity to enhance precision immunotherapy is also exemplified on this slide as shown we can easily swap tumor specific T cell targeting modules to cover many different cancers cue 101 serves as a beachhead that provides not only a registrational path for HPV driven cancers, but also provides proof of <unk>.
Concept for developing additional immuno stats for different cancers by targeting shared tumor antigens personalized tumor antigens and or neo antigens.
Extensibility as highlighted by Q1 or two that targets wilms tumor one for multiple indications and by preclinical validation of additional immuno stats that incorporate important tumor targets such as mutated chaos MAGE et cetera.
The other aspect of plateau modularity allows us to incorporate multiple HLA illegals to expand patient.
Global patient coverage, we've already demonstrated this versatility by generating immuno stats with HLA <unk> III, a $11 24 as examples on the next slide Slide 22 gives us nap shot of our current pipeline in oncology and autoimmunity.
We remain focused on our clinical stage assets that is Q1, a one on one or two which continue to generate data demonstrating patient benefit and evidence of durable clinical activity. We believe this validation positions us strongly to expand our pipeline into additional indications as mentioned to that end, we have pre clinically validated several different immuno stats that can be progress.
Into clinical stage assets. We are currently engaged in strategic discussions to map the path forward for our oncology pipeline assets. Let me briefly comment on our autoimmune pipeline earlier. This year, we announced the collaboration with Ono Pharmaceuticals to develop Q4 hundred one as a therapeutic for many autoimmune disorders Q4 hundred one.
<unk> is a novel bi specific molecule for induction in expansion of regulatory T cells or T regs.
Many IL two mid teens are being developed for enhancing the small subset of natural T. Regs. In contrast to these mute teens Q4 hundred one is composed of an IL two variant and the TGF beta variant. Both these cytokines together have been demonstrated to generate new populations of T. Regs also known as induced T. Rex.
As well as expand the preexisting natural T Rex.
Hence we believe this dual mode of action differentiate Q4, one from all other IL two muting and holds the promise to reset the immune balance we continue to make very good progress with this asset and are actively generating data sets that support us moving forward towards an IND.
We also continue to be engaged in discussions to further develop additional assets within our autoimmune pipeline with that synopsis I will pass the call to carry to review our financial data Kerry. Thanks, Denise I'd like to provide a brief update on our financial results for the three and six months ended June 32023 as shown on slide 23 during the <unk>.
Second quarter of 2023, and the company continues to use its resources in a disciplined and efficient manner, while maintaining a consistent level of overall spend when compared to the same period. In 2022 Importantly, we reported collaboration revenue of approximately $1 4 million for the three months ended June 32023, as compared to 26.
For the three months ended June 2022.
Revenue in the second quarter of 2023 was due to work related to the recent collaboration and option agreement with Ono Pharmaceuticals.
And he's just mentioned.
As of June 32023, the company had approximately $57 9 million in cash cash equivalents and marketable securities compared with $66 1 million as of June 32022.
Our current cash position includes proceeds from the sale of shares of our common stock in July under the October 2021, ATM agreement with Jefferies.
Our current cash position cash equivalents and marketable securities to fund operations through the third quarter of 2024, I will now turn the call back over to Dan for closing their ask Dan Yes. Thanks Kerry.
So in summary, we view the updated data from our ongoing trials with cue 101 in Q1 O two to be foundational representing breakthrough potential by enabling what we consider to be precision activation of the patient's own immune system to destroy cancer.
Furthermore, in combination with existing standard of care therapies, such as checkpoint inhibitors Amin SaaS may significantly expand patient reach and clinical efficacy. These developments could be transformational for the future of cancer immunotherapy.
And our Q1 O. Two trial, we're very pleased to already observed metrics of anti tumor activity in several patients in the dose escalation portion.
Furthermore, and increased demand for patient access to our trial.
We believe underscores the therapeutic platforms potential in addressing the.
A significant unmet medical need for these patients, especially since many of these cancers have largely been unresponsive to checkpoint inhibitor therapy.
Our platform versatility and modularity also offers market expansion opportunities into additional indications and broad HLA coverage to treat global patient populations.
We also believe the application of our platform in autoimmune diseases and he's just touched upon.
More specifically Q4 O. One holds blockbuster market potential as a possible treatment for a myriad of autoimmune diseases. We continue to make impressive progress forward with our partner Ono pharmaceutical and we look forward to providing further details on this program later in the year.
I want to thank everyone listening in particularly our shareholders for their support and appreciate the ongoing interest in our important progress for developing promising therapeutics for patients in need.
Speaking of I want to thank the patients participating in our trials as well as their families for support I also want to thank our dedicated employees for their commitment and consummate professionalism for bringing these promising therapeutic candidates forward.
With that I'll now turn the call over to the operator and open up for any questions operator.
Thank you ladies and gentlemen, we will now begin the question and answer session. So do you have a question. Please press the star followed by the one on you touched on form you will hear three tone prompt acknowledging your request questions will be taken in the order received should you wish to withdraw your request. Please press the star followed by the two if you are use.
A speaker phone please lift the handset before pressing the keys one moment. Please for your first question.
Your first question comes from Ted <unk> from Piper Sandler. Please go ahead.
Great. Thank you very much.
Yes.
Thank you for the update and congrats on the strong data to date.
You guys are presented with sort of.
Win win scenario here.
Where are you.
You are seeing can enhance activity on top of Keytruda in frontline lung with 101 as well as monotherapy in later stage patients.
What goes into the process throughout the rest of the year as we generate more data.
I look forward to that.
What really is going to go into that process.
But beyond that.
What other factors.
Strategic or financial how does all of that kind of come together to sort out.
Your path forward. Thank you.
Yes, Thanks, Ted this is Dan.
I appreciate the question.
Yes, it is a.
Dilemma, because we have positive data on both fronts, but more importantly.
We're a.
Platform company, not a head neck cancer company.
We have limited resources. So we're thinking on a very strategic level. This obviously has to do with our corporate development initiatives partnering initiatives, what's the best strategy for <unk>.
Developing both this particular asset in various.
Scenarios monotherapy.
Combination, we do plan to.
Have a meeting with the FDA in the coming months and that will define.
Possible registration path and I think that would also be an asset for strategic.
Partnering discussions as well.
But we also have this data emerging from Q1 O two as a monotherapy in cancers that by and large have not been responsive to checkpoint inhibition and if we can demonstrate that we are turning these.
Cold tepid tuners into tumors into hot tumor tumors.
And expanding patient reach that's going to put us in a.
Enviable position in terms of enabling.
The application of checkpoints in cancers that have previously not been available. So we're looking at all of this obviously in a pragmatic strategic manner. We're looking at various strategic scenarios and we're in ongoing dialogue with our board, which ultimately.
<unk>.
As part of this decision process. So I appreciate the question.
It's an important one for us to continue to define and refine and I think in essence, we're going to have a decision tree based on pros and cons based on capital access requirements cost of capital in all of our various alternatives on strategic partnering.
And all of these are good problems to have we just have to address them head on and in a timely manner going forward.
Great.
I'll hop back in the queue.
Thank you.
Thank you. Your next question comes from Ren Benjamin from JMP Securities. Please go ahead.
Hey, guys. Thanks for taking the questions and congratulations on all the progress I have a couple of questions.
Couple of questions, maybe just starting off with the monotherapy study and the update on overall survival can you talk a little bit about what additional information is really needed from the study.
You can kind of like book the appointment with the regulatory body have your discussion and what would you consider it to be a.
Trial design agreement win if you will.
In terms of once you've had that meeting and then I have a couple of follow ups.
Sure.
I'm going to ask Matteo to handle that question.
Yes.
Certainly so thanks for the question.
As this data has matured and the cohort of 20 patients treated at four <unk>.
It's really strengthened now with with an approximate median OS of.
14.
Months, which really compares very favorably to to that which was observed EBIT in the second line setting at eight months, so a component of it.
Planned FDA interaction is to put forth a proposal for a registrational trial.
We've developed a synopsis and design for that trial, and it's basically a randomized trial.
Most likely.
It's two to one randomization of cue 101 monotherapy to serve investigator's choice of three potential chemotherapeutic regimens.
So we have.
All of the details and statistical parameters defined.
And.
And our interaction with FDA.
With regards to when it's really we anticipate.
Having if you will.
Endorsements quote unquote.
For a single Registrational trial to support an approval.
In late line patients.
Got it.
And then just switching gears you know because I know we've talked in the past about.
The Neo adjuvant study the importance of the Neo adjuvant study.
Might have missed it in the prepared remarks, but can you can you talk a little bit about kind of where we are when we might expect to see any data and how.
How that program might ultimately move forward.
Matteo I think Thats also ya.
Yes, certainly so so the new adjuvant trial at Washington University is going very very well, okay and the trial is currently enrolling patients in the second schedule, which is.
Patients are getting two doses of Q.
101.
Before.
Treatment with curative intent, either surgery or chemo or T cell.
It is important to note that this is a <unk>.
The Gators sponsored trial and so the timing of <unk>.
Sharon and presenting this data.
Will occur as a collaboration.
With the group there that hold the IND for the Isd.
We have seen some early data that looks very encouraging.
So we really feel that this will.
Further our understanding of Q1's effect in the tumor microenvironment.
Since the analyses and characterization of tissue based <unk> blood based immune markers.
And even T cell receptor presence in the tumor pre.
And post treatment really is going to be really an exciting data set to look at when it is presented with our collaborators.
Got it.
And then I guess, just finally, as we think about Q1 O.
Oh, sorry, Q2 of one I think.
Going after there'll be two one.
Can you you mentioned on the call clinics.
Clinical activity that you've seen.
Can you maybe provide some additional color on those responses in the tumors, where you saw an impact and maybe related to that as you think about that program moving forward.
How should we be thinking about the ideal combinations and the potential to sequence with subsequent checkpoints.
Certainly so thanks, thanks for the question so.
To begin the next steps are really to determine the recommended phase two dose. Okay. So that is the primary objective of the of the dose escalation component.
With regards to the activity that we're observing okay. We have four.
Cancer types here.
And as we've stated we've seen now a reduction.
That's been sustained for over 18 weeks in a patient with advanced metastatic gastric cancer. We have several patients now that have stable disease confirmed up to 18 weeks so across different indications. So so we look forward to presenting the formal analysis of what we've seen with regards to.
Two effects on tumors at the at the city meeting with regards to where we'll be going I think.
Once we establish the monotherapy activity okay in these various indications.
Indications that will certainly.
<unk> assess rational combinations to consider taking forward.
And really importantly, I think.
Understanding that the unique biology of different tumor types. Okay may really direct based on the data where it would make sense to combine cue 102. So so we look forward to seeing that just as an example, colorectal cancer.
<unk> believed are pretty much accepted that part of the resistance to checkpoint inhibitors in immunotherapy is borne out of a dominant immunosuppressive environment and so in that tumor type it would make sense to consider combining with something that that that interferes with that immunosuppressive pathway. It could be a teekay <unk> it could be another.
<unk> agents. So so so that's where we'll be.
Heading in for example in gastric cancer I think.
There's been some activity with checkpoint inhibitors. There is a an approval in her two positive subset of gastric cancer for Pembroke plus her two targeting agent.
That may be a cancer indication, where it would make sense that combined with an anti PD, one or other checkpoint inhibitor.
And.
That's what I think will be considering.
Terrific. Thanks, very much for taking the questions and good luck. Thanks Ryan.
Thank you. Your next question comes from Stephen Willey with Stifel. Please go ahead.
Uh huh.
Hi, guys. Good just to lay on car Ts can you guys hear me okay.
We can hear you just fine. Thank you okay. Great. Thank you. Thank you for taking my question. So I have two questions on my land, that's going with the cue 101.
Plots pins on the map the combination cohort do you think you guys were.
Pursue specific target population moving forward.
Could you guys mentioned a lot about how this company can improve low CPA.
No secret square population, even better compared to let's say high for example, do you think there will be any potential signal indication that you guys would be tied to specific population. So that relates to your Q1 O. One and regarding Q1 of two can you. Please.
Provide little more color on enrollment dynamics and maybe.
Possibly.
I'll give you a comment on like how many patients have been enrolled so far and if possible maybe additional color on like data disclosure deed update.
Great.
That's all on my end, thank you very much.
Thank you I think the first question has to do with stratify them with Cps score.
Got it.
I'm happy to take these two great.
Great questions. So with regards to Q1 O one in Pampa Lindsay Mab and the data that we're observing right where we have a.
Really meaningful.
Tripling our response rate in the Cps low population.
Also we have about one six times increase in the Cps high population.
The way I think we're thinking about this is this is actually really a win win for any patients that are being treated in the first line setting with a checkpoint inhibitor such as timber lithium that so so if you actually look at the data on.
On the low population.
Less than one in five patients that benefit or have a response and so if we can push that up to 50%.
Fantastic.
For the patients and then even in the Cps Hi.
Population, we have a clear benefit of improving the activity. There. So so I think where things stand now <unk> is approved in the first line for treating any patients that are cps greater than or equal to 1%.
And it's not clear that stratification.
Really what would be needed or specific targeting since really all of these patients appear to benefit more from the combination.
With regards to Q1 O two.
The enrollment is in my experience has been close to the the.
Fastest for a dose escalation phase one advanced cancer study and as I mentioned before this is really borne out of the remarkable enthusiasm of the investigators and I think also it underscores the large unmet need of patients with.
Advanced disease and these these four indications.
Regarding the numbers of patients I think we anticipate presenting the initial data on approximately 20 patients or more.
<unk> in November and the data that we'll be presenting at that time is the initial observations on the safety and Tolerability.
Q1 O two monotherapy.
We have already and we will fill out more some preliminary pharmacokinetic data from the dose escalation patients characterized the clinical course, that's been observed and also share any correlate the data sets that we have available at that time as I'm sure you know well, we're working very actively with several different.
Vendors that aren't going to help us do the qualitative analysis and we hope to have some of that data to share as well.
Thank you very much.
Okay.
Thank you, ladies and gentlemen, as a reminder, so do you have a question. Please press the star followed by the one.
Next question comes from Peter <unk> with Oppenheimer. Please go ahead.
Okay.
Hey, guys, it's Trevor.
Thanks for taking the question.
So you just see the see updates.
So looking ahead to 2024 can you guys discuss some of the additional data we might see it throughout the year there.
Yes 2024.
Obviously, we'll have resolution from our FDA discussions with the strategy is on 101 I'm also clarity on.
Our strategic decision on.
What indication of what.
Line.
Frontline third line both.
In 2024, we should have.
So the decision of.
Whether we're partnering 101.
And with whom what structure one.
102, as Matteo just articulated we have.
A very enviable position, where we have multiple cancers. We've seen early activity in dose escalation just to reiterate what matteo conveyed during the call we've.
We're seeing activity at the one Meg and two Mig dose level. So we also have the scans for four and eight we'll be providing at Citi. So going into 2024, there's going to be a pretty exciting year just from a standpoint of prioritizing.
Obviously in this current financial climate, we have.
Resource requirements that were going to have to address so most likely to a strategic.
We also have data from 401 that is emerging we will have clarity by end of year going into 2024, we consider that to be a really important transitional year for us. So I think it's going to be a year of multiple milestones that will be clearly defining by the end of the year.
As well as pipeline decisions, Okay I appreciate it.
Thank you at this time there are no further questions. Please proceed with your closing remarks.
Yeah, I want to thank everyone for your time and interest in our continued progress.
Hi.
Clearly, making very good steady progress as we move forward and we're looking forward to city and providing you with further updates as we continue developing for the remainder of the year.
Wish everyone.
Pleasant remainder of the week and again, thank you for your interest and take care.
Yes.
Okay.
This concludes your conference call for today, you May now disconnect your lines. Thank you.
Yeah.
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Okay.
Yeah.
Yes.
Thank you.
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