Cue Biopharma Q2 2023 Earnings Call Transcript

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Provided by Quartr
August 9, 2023

There are 8 speakers on the call.

Operator

Greetings, and welcome to the Q Biopharma Investor Update Call. At this time, all participants are in a listen only mode. A question and answer session will follow the presentation. As a reminder, this conference is being recorded. I would now like to turn the conference over to Dan Pesari, Q Biopharma's Chief Executive Officer.

Operator

Thank you. You may begin.

Speaker 1

All right. Thank you very much and good afternoon everyone. As a reminder, this presentation and discussion is being Joining me on today's call is Doctor. Anish Suri, our President and Chief Scientific Officer Doctor. Matteo Lovasetti, our Chief Medical And Karri Anne Millar, our Chief Financial Officer.

Speaker 1

As shown on Slide number 2, This presentation and overview may contain some forward looking statements and any forward looking statement made during call represents the company's views only as of today, August 9, 2023. On the next slide, which is Slide number 3, It just outlines the agenda for today's call, and I'll begin with a brief summary followed by Anish. Anish will provide you with some background context pertaining to our approach And resulting developments regarding the Immunostat platform with a brief synopsis of associated competitive advantage Pertaining to the observations from our ongoing clinical trials. Following the background provided by Anish, Matteo will then provide An update on observations from our ongoing clinical development regarding mechanistic insights having corporate development implications Our ongoing corporate strategic positioning. Both Anish and Matteo, during the presentation, will be providing updates with some of the data and slides having been Previously presented and discussed on prior calls, the repeat of that data is meant to provide context 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.

Speaker 1

Following, Matteo, Anish will return With a brief overview of our preclinical pipeline developments and then that will be followed by Keri, who will provide an overview of our financials for Q2 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 Anish. Anish?

Speaker 2

Thanks, Dan. As noted in Slide 4, the foundational premise and vision for our therapeutic platform has centered on harnessing the natural signals or nature's cues 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 what evolution has already refined, which is the herculean task of creating molecules and signaling pathways that lead to balanced immune responses. Most importantly, these signals or Nature's cues have been fine tuned and optimized to provide protective immunity while preserving the safety Using these underlying principles of selectivity, we have engineered and now clinically validated A new class of bispecific T cell engagers termed immunostats 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 deliver natural immune activation signals such as the cytokine IL-two selectively to the tumor specific T cells.

Speaker 2

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 breadth 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 position us to exploit the breadth of our Okay.

Speaker 2

The next slide, Slide 5, provides a conceptual framework for maximizing the success By deploying immunostats, we have the potential to solve a significant and fundamental challenge, which is the selective activation of the rare population of T cells that express T cell receptors or TCRs 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 bispecifics, checkpoint inhibitors or untargeted 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 6 provides additional details into the design and functional engages of TCRs of tumor specific T cells and deliver functional IL-two signals to those very T cells.

Speaker 2

The Q100 series architecture is composed of 2 natural signals. 1 is the stabilized peptide HLA complex or PHLA That selectively binds to only the tumor specific T cells. Note that the specificity is driven by the T cell leptote 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's selective design and hence results in exquisite specificity.

Speaker 2

The generation of a therapeutic index for the right tumor specific T cell over all other irrelevant T cells It's further supported mechanistically by the elegant live cell microscopy experiments conducted by Doctor. Michael Duston's lab at University of Oxford. Doctor. Dustin 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 immunostat with the antigen specific T cells, that is the T cell bearing the right T cell receptor, Results in formation of an immune synapse and TCR clustering and activation as shown in green.

Speaker 2

When the same immunostat engages an irrelevant T cell, no such effect Before I pass the call to Matteo, I'll summarize our key highlights and accomplishments as shown in Slide 7. To note, we have developed a novel first in class biologics platform and have treated over 80 patients thus far with evidence of antitumor efficacy and tolerability. Importantly, we've had patients in our trials that have continued to receive drug for up to 2 years, underscoring the durability of the clinical activity and the 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.

Speaker 2

In the frontline setting where anti PD-one therapy is approved, We have combined our immunostats to demonstrate a 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 It is well recognized that patients with low CPS scores constitute a significant population and are notably less responsive The checkpoint inhibitor therapy. One possible explanation for the significant increase in responses in CPS low patients May pertain to the observation that immunostats increase 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, Q101's maturing clinical profile in both The monotherapy and combination trials provides us with a range of potential long term development and strategic opportunities.

Speaker 2

We also believe that the clinical data with Q101 have validated and derisked our broader platform. To that end, the FDA acknowledged that the clinical and safety data from Q101 Provided sufficient confidence to allow the acceptance of our second IND with Q102 without the need for additional IND enabling toxicology studies And allowed us to start the Q102 monotherapy dose escalation at the clinically active dose of 1 MYC per kg. The latter point Shortened our dose escalation in patients significantly and saved us approximately a year in clinical development timelines. We believe these unique 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 Q100 series immunostats.

Speaker 2

The primary difference is at the level of the tumor antigen specificity or the PHLA part. For example, Q101 and Q102 are 99% sequence identical, Except for the tumor antigen T cell epitope, hence providing a very modular framework for development of distinct therapeutic molecules against a wide range of cancers. Lastly, from a manufacturability and cost of goods perspective, immunostats are manufactured using established and conventional CMC protocols For monoclonal antibodies and Fc fusion proteins, our yields are similar to monoclonal antibodies in grams per liter and GMP stability has been impressive. For example, Q101 has a shelf life that goes north of 3 years, which is comparable to or better than most monoclonal antibodies. With that synopsis, I will now pass the call to Matteo to provide the most recent clinical update for Q101 and Q102.

Speaker 2

Matteo?

Speaker 3

Thanks, Anish. The clinical data from the ongoing Q101 trial continues to demonstrate highly encouraging In a robust metrics of clinical benefit for heavily pretreated recurrent metastatic HBV positive head and neck cancer patients Treated with monotherapy and for newly diagnosed patients with recurrent metastatic HPV positive head and neck cancer treated in combination with pembrolizumab. As shown on Slide 8, data from the ongoing clinical trials with Q101 as monotherapy and in combination with pembrolizumab have Provided clinical proof of concept in derisking of our immunostat platform. The latest data generated to date in 2023 Continues to support prior observations and further enhances our confidence in Q101 as a potential therapeutic As previously and consistently stated, we believe Q101's mechanism of action, as evidenced by the ongoing data generated to date, provides effective and tolerated dose levels, Current metastatic HBV 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 Q101 is in fact stimulating the targeted cancer specific T cells within these patients, resulting in demonstrable antitumor effect.

Speaker 3

Furthermore and importantly, we continue to observe an evolving pattern of disease control In enhanced survival in the monotherapy trial, we believe this enhanced survival is due to the persistent expansion of tumor specific T cells given Q101's mechanism of action, especially in the tumor microenvironment. As shown on previous webcast, I'd like to review the data on Slide 9. As it is very important to understand the mechanistic differentiating features of Q101, including its effects on NK cells and tumor specific T cells in the blood and the tumor microenvironment. In clinical trials to date, Q101 demonstrates well behaved and consistent pharmacokinetics with low inter patient variability at the RP2D 4 milligrams per kilogram. The exposure pattern is consistent throughout multiple cycles of treatment without any attenuation of PK parameters Reporting the premise that there is no evidence of clinically relevant immunogenicity.

Speaker 3

Regarding its pharmacodynamic or PD profile, Q102 treatment also results in a consistently observed sustained increase in natural killer cells or NK The positive attribute associated with an anti tumor response as NK cells are known to induce potent tumor killing. Importantly, 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 E7 Reactive T cells in the peripheral blood of patients as early as 1 week after administration of Q1 101.

Speaker 3

Paired 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 Q101 monotherapy as well as that observed when combined with a checkpoint inhibitor. In addition to the favorable PK and PD just described in patients with advanced HBV 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 are observed with Q101 monotherapy. As shown on the left, patient A experienced a durable partial response with an approximate 60% reduction in tumor burden evident at 6 weeks After the first two cycles of Q101, which lasted close to 1 year on therapy.

Speaker 3

Importantly, this patient Also demonstrated a significant reduction in HPV cell free DNA that coincided with the initiation of the partial response And HBV cell free DNA remained undetectable for the majority of time on treatment. Patient B, who just completed 24 months of treatment, This had durable stable disease with tumor burden reduction 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 6. The undetectable HBV cell free DNA, which is an increasingly recognized biomarker of disease activity, Is suggestive of a pathologic complete response, I. E.

Speaker 3

A potential cure in this patient, who we expect may at some point Have a surgical resection of the lesion for histopathological analysis. Patient C has experienced Tumor reduction after a prolonged period on drug where no resist based objective response was initially observed by imaging. After approximately 6 months on treatment, the tumor began to shrink and the patient remained on therapy for greater than 18 months after starting treatment with Q101. As shown on Slide 11, the current median overall survival observed in the 20 patients Treated at the recommended Phase 2 dose of 4 milligrams per kilogram is approximately 14 months. The observed median overall survival of 14 months in patients treated in the 3rd line and beyond is notable when compared to the historical median overall survival of approximately 8 months Observed in patients treated in the 2nd line trials, CheckMate 141 and KEYNOTE-forty trials Of nivolumab and pembrolizumab, respectively.

Speaker 3

As any experienced oncologist understands, the survival with third line treatment is expected to be less as the Our evolving data continues to support the premise that treatment with Q101 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 HBV positive head and neck cancer. Based upon the strength of this data, we plan to meet with FDA to As indicated on Slide 12, I will now provide an update Pembrolizumab is approved for the treatment of first line patients with recurrent metastatic head and neck cancer that have tumors with CPS scores greater than or equal to 1%. CPS is a measure of PD L1 expression in the tumor. As shown on Slide 13, the distribution of PD L1 expression observed in the KEYNOTE-forty eight study population Shows that approximately 50% of CPS positive patients have CPS values of 1 to 9 and the other 50% have CPS values greater Subgroup analysis of the KEYNOTE-forty eight study has shown that patients with CPS of 1 to 19 At lower overall response rates, lower median progression free survival and lower overall survival compared to the patients with CPS and to improve outcomes for all patients treated with checkpoint inhibitors.

Speaker 3

The next slide, Slide 14, Shows the current overall response rate of 44% observed in first line patients treated with the Q101 and pembrolizumab as discussed on the June 14 earnings call. Since that call, we have observed 2 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 Which I will describe in detail momentarily. In addition to the confirmed complete response, 6 of the first 16 evaluable patients treated at the RP2D of Q101 and pembrolizumab have experienced partial responses now with all 6 confirmed. Partial response is defined as a reduction of tumor burden of greater than 30% of 30% or greater An additional 2 patients that have experienced greater than 20% reductions in the sum of target lesions remain on treatment.

Speaker 3

The confirmed overall response rate The 44% observed in patients with CPS greater than or equal to 1 treated with Q101 In combination with pembrolizumab to date compares favorably to the historical response rate of 19% observed with pembrolizumab Monotherapy in the KEYNOTE-forty eight study. Notably, 4 out of 8 or 50% of the combination patients with low PD L1 Threat expression, I. E, CPS scores of 1 to 19 experienced objective responses, which is greater than the expected rate of approximately 14% As such, Q1-one appears to significantly enhance the response rate of anti PD of PD-one inhibition, particularly in patients that have low PD L1 expression, which represents approximately half of the patients eligible for treatment with a checkpoint inhibitor in the frontline The next slide, Slide 15, shows the overall response rates observed in subgroups of patients treated with pembrolizumab alone According to CPS values in the KEYNOTE-forty eight trial compared to the overall response rates observed with Q101 and pembrolizumab combination therapy. As shown, pembrolizumab demonstrates lower efficacy in tumors with low CPS scores. Specifically, an overall response rate of 14% was observed with CPS scores of 1 to 19 compared to an overall response rate of 23% That was observed with CPS scores of greater than 20 in the KEYNOTE-forty eight study.

Speaker 3

For all patients with CPS scores greater than or equal to 1, An overall response rate of 44% was observed in Q101 and pembrolizumab, which represents a greater than doubling The historical response rate of 19% observed with pembro alone. Notably, for patients with CPS scores of 1 to 19, An overall response rate of 50% was observed with Q101 and pembrolizumab, which represents a greater than tripling of the Historical response rate of 14% observed with pembro alone. Furthermore, Q101 also appears to increase the response rate in patients With CPS scores greater than 20, with an overall response rate of 38% for Q101 and pembrolizumab And a response rate of 23% for pembro alone. In totality, our data suggests that not only does Q101 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, I.

Speaker 3

E. 1 to 19 Represent approximately 50% of all patients that are eligible to receive pembrolizumab. Additional data on the patient with the now confirmed CR shown on Slide 16 demonstrates the time course of The patient had a target disease burden of approximately 8 centimeters, Partial response was observed at the first scan at 6 weeks and a complete response was observed in the tonsil lesion at 18 weeks. At week 42, a complete response was observed in all target lesions followed by a complete response in all Radiologic evidence of disease at 48 weeks. The complete response was confirmed on scans performed at week 54.

Speaker 3

2 of the target lesions were lymph nodes and they have reduced in size to less than 10 millimeters, I. E. The size of a normal lymph node, which in addition to the other findings meets 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 2 dose in The ongoing combination trial of Q101 remain alive as of the last follow-up for each patient. As an update, we just recently treated the 18th patient at the recommended Phase 2 dose and have 4 additional patients in screening.

Speaker 3

Of note, 9 patients remain on treatment and to date Five patients have lived beyond 12 months, which was the median overall survival observed in patients treated with pembrolizumab alone in the KEYNOTE-forty eight study. The swimmer plot also shows an emerging trend of extension of progression free survival in patients treated at the recommended Phase 2 dose Q101 and pembrolizumab. 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 Tumor efficacy evidenced by resist based partial response in durable stable disease in third line and beyond recurrent metastatic head and neck cancer patients And immediate overall survival benefit from survival follow-up in the recommended Phase 2 dose cohort. As previously announced, the robust data on Q101's activity in monotherapy and in combination with pembrolizumab enabled the granting of fast 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 cumulative data from these ongoing trials with Q101 have provided us with clear evidence of Targeted expansion of HPV E7 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 enhance efficacy of checkpoint blockade therapy.

Speaker 3

As such, we believe Q101, Our first biologic therapeutic from our Q100 series represents a potential therapeutic breakthrough for patients. Furthermore, we believe the data from Q101 has provided a derisking and mechanistic validation for additional biologics From the IL-two based Q100 series beginning with Q102. As a reminder, shown on Slide 19, Q102 and Q101 share 99% amino acid sequence identity. This enabled us to significantly decrease the development time and cost of Q102 As we're not required by the FDA to repeat IND enabling toxicology studies for Q102 and we are also able to initiate the Phase 1 dose We are conducting the Q102 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.

Speaker 3

Findings observed to date are summarized on Slide 20. 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 in WT1 expressing We are currently enrolling patients at 8 milligrams per kilogram and expanding the 2 and 4 milligram per kilogram cohorts. Q102 has been well tolerated to date with no dose limiting toxicities observed. Evidence of anti Tumor activity has already been observed in heavily pretreated patients, including reductions in target lesions, stable disease and reductions in tumor markers in several patients.

Speaker 3

For example, a patient with gastric cancer that progressed in 3 prior lines of therapy, including a checkpoint inhibitor, has experienced a decrease In the sum of 3 target lesions of approximately minus 25% seen on scans at weeks 6, 12 18 and the patient currently continues on treatment. These early signs of clinical activity are particularly encouraging as they were observed At the 1 milligram per kilogram and 2 milligram per kilogram dose levels, with the scans on the patients dosed at 4 milligrams and 8 milligrams per kilogram are currently pending. We are encouraged by these early observations of monotherapy anti I will now turn the call over to Anish. Anish?

Speaker 2

Thanks, Matteo. As discussed by Matteo, the clinical validation data with Q101102 provides us enormous confidence to exploit the breadth of our platform to cover many cancers. As shown in Slide 21, the core IL-two framework for each distinct immunostat remains constant. The primary difference between each molecule Is the T cell targeting moiety, which is unique to the cancer specificity. In other words, these different immunostats are essentially analogs of each other.

Speaker 2

To that end, we believe that the clinical experience with our first clinical candidate Q101 provides platform validation and platform derisking. 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. The 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. Q101 serves as a beachhead that provides not only a registrational path for HPV driven cancers, but also provides proof of concept for developing additional immunostats for different cancers by targeting shared tumor antigens, personalized tumor antigens and or neoantigens.

Speaker 2

This extensibility is highlighted by Q102 that targets Wilms Tumor 1 for multiple indications and by preclinical validation of additional immunostats that incorporate important tumor targets such as mutated KRAS, MAGE, etcetera. The other aspect of platform modularity Allows us to incorporate multiple HLA alleles to expand patient global patient coverage. We've already demonstrated this by generating immunostats with HLA AO2, AO3, A11 and A24 as examples. The next slide, Slide 22, gives a snapshot of our current pipeline in oncology and autoimmunity. We remain focused on our clinical stage assets That is Q101102, which continue to generate data demonstrating patient benefit and evidence of durable clinical activity.

Speaker 2

We believe this validation positions us strongly to expand the pipeline into additional indications as mentioned. To that end, we have pre clinically validated several different immunostats that can be progressed 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 Q401 As a therapeutic for many autoimmune disorders, Q401 is a novel bispecific molecule for induction and expansion of regulatory T cells or Tregs.

Speaker 2

Many IL-two mutants are being developed for enhancing the small subset of natural Tregs. In contrast to these mutants, Q4-one is composed of an IL-two variant and a TGF beta variant. Both these cytokines together have been demonstrated to generate new populations of Tregs, also known as induced Tregs, as well as expand the pre existing natural Tregs. Hence, we believe this dual mode of action differentiates Q4 And holds the promise to reset immune balance. We continue to make very good progress with this asset and are actively generating data sets that support us moving We also continue to be engaged in discussions to further develop additional assets within our autoimmune pipeline.

Speaker 2

With that synopsis, I will pass the call to Keri to review our financial data. Keri?

Speaker 4

Thanks, Dinesh. I'd like to provide a brief update on our financial results For the 3 6 months ended June 30, 2023, as shown on Slide 23, during the Q2 of 2020 The company continued 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 $1,400,000 for the 3 months ended June 30, 2023, as compared to 26,000 for the 3 months ended June 2022. Revenue in the Q2 of 2023 was As of June 30, 2023, the company had approximately $57,900,000 in cash, cash equivalents and marketable securities Under the October 2021 ATM agreement with Jefferies, we expect our current cash position, cash equivalents and marketable securities to fund operations through the Q3 of 2024. I'll now turn the call back over to Dan for closing the rocks.

Speaker 4

Dan?

Speaker 1

Yes. Thanks, Carrie. So in summary, we view the updated data from our ongoing trials with Q101 And Q102 to be foundational, representing breakthrough potential by enabling, 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, Immunostats may significantly expand patient reach and clinical efficacy. These developments could be transformational for the Future of cancer immunotherapy.

Speaker 1

At our Q102 trial, we're very pleased to already observe metrics of antitumor activity in Several patients in the dose escalation portion. Furthermore, an increased demand for patient access to our trial, We believe underscores the therapeutic platform's potential in addressing the 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 We also believe the application of our platform in autoimmune disease, as Anish just touched upon, more specifically Q4 1 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 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 and 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.

Speaker 1

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?

Operator

Thank you. Ladies and gentlemen, we will now begin the question and answer Your first question comes from Ted Tenthoff from Piper Sandler. Please go ahead.

Speaker 5

Great. Thank you very much. And Thank you for the update and congrats on all the strong data to date. You guys are presented with Sort of a win win scenario here, where you're seeing enhanced 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 you generate more data and we're looking forward to that at SITC. What really is going to go into that process?

Speaker 5

And even beyond the data, what other factors, whether they be strategic or financial, how does all that kind of come together to sort of Chart your path forward. Thank you.

Speaker 1

Yes. Thanks, Ted. This is Dan. Appreciate the question. Yes.

Speaker 1

It is a dilemma because we have positive data on both fronts, but more importantly, we're a Platform company, not a head and neck cancer company, and we have limited resources. So we're thinking on a very strategic level. This It has to do with our corporate development initiatives, partnering initiatives, what's the best strategy for 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 our strategic Partnering discussions as well. But we also have this data emerging from Q102 as a monotherapy in cancers that by and large have Not been responsive to checkpoint inhibition. And if we can demonstrate that we're turning these cold tepid tumors into hot tumors And expanding patient reach, that's going to put us in an enviable position in terms of enabling The application of checkpoints in cancers that have previously not been available.

Speaker 1

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 It's part of this decision process. So I appreciate the question. It's an important one for us to continue to define and refine. 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 and our various alternatives on strategic partnering. And all of these are they're good problems to have.

Speaker 1

We just have to address them Head on and in a timely manner going forward.

Speaker 5

Great. Thank you. I'll hop back in the queue.

Speaker 1

Thank you.

Operator

Thank you. Your next question comes from Ren Benjamin from JMP Securities. Please go ahead.

Speaker 6

Hey, guys. Thanks for taking the questions and congratulations on all the progress. I have a couple

Speaker 1

of questions.

Speaker 6

Thanks, Jay. A 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 so that you can kind of like book the appointment with the regulatory body, have your discussion. And what would you consider 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.

Speaker 1

Sure. I'm going to ask Matteo to handle that question.

Speaker 3

Certainly. So thanks for the question. As this data has matured in the cohort of 20 patients Treated at 4 mgs per kg, it's really strengthened now with an approximate median OS Of 14 months, which really compares very favorably to that which was observed even in the second line setting at 8 months. So component of the 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, 2 to 1 randomization of Q101 monotherapy To serve investigators' choice of 3 potential chemotherapeutic regimens. So we have all of The details and statistical parameters are defined.

Speaker 3

And so in our interaction with FDA, With regards to win, it's really we anticipate having, if you will, Endorsements for a single registrational trial to support an approval in late line patients.

Speaker 6

Got it. And then just switching gears, because I know we've talked in the past about The neoadjuvant study, the importance of the neoadjuvant study, I might have missed it in the prepared remarks, but can you talk a little bit about Kind of where we are, when we might expect to see any data and how that program might ultimately move forward?

Speaker 1

Yes. Matteo, I think that's also you.

Speaker 3

Yes, certainly. So the new adjuvant trial at Washington It's going very, very well. Okay. And the trial is currently enrolling patients in the second schedule, which is Patients are getting 2 doses of Q101 before Treatment with curative intent, either surgery or chemoRT. So, important to note that this is an investigator sponsored trial.

Speaker 3

And so the timing of sharing and presenting this data will occur as a collaboration With the group there that hold the IND for the IST, we have seen some early data that looks very encouraging. And so we really feel that this will further our understanding of Q101's effect in the tumor microenvironment Since the analyses and characterization of tissue based TME, blood based immune markers And even T cell receptor presence in the tumor pre and post treatment really It is going to be really an exciting dataset to look at when it is presented with our collaborators.

Speaker 6

Got it. And then I guess just finally as we think about Q1 Sorry, Q2-one, I think, going after WT-one. Can you you mentioned on the call Clinical activity that you've seen, can you maybe provide some additional color on those responses and 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?

Speaker 3

Certainly. So thanks for the question. So, to begin, the next steps are really to determine the recommended Phase 2 dose, okay. So that is the primary objective of the dose escalation component. With regards to the activity that we're observing, okay, we have 4 cancer types here.

Speaker 3

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 We have several patients now that have stable disease confirmed, up to 18 weeks, So across different indications. So we look forward to presenting the formal analysis of what we've seen with regards to effects on At the SITC meeting. With regards to where we'll be going, I think once we establish the monotherapy activity, Okay. In these various indications that will certainly assess rational combinations to consider taking forward. And really importantly, I think, understanding that the unique biologies of different tumor types, okay, May really direct based on the data where it would make sense to combine Q102.

Speaker 3

So we look forward to seeing that just as an example, in colorectal cancer, it's I think believed or pretty much accepted that Part of the resistance to checkpoint inhibitors in immunotherapy is born out of a dominant immunosuppressive environment. And so in that tumor type, it would make sense To consider combining with something that interferes with that immunosuppressive pathway, it could be a TKI, it could be Another agent. So that's where we'll be heading. And for example, in gastric cancer, I think There's been some activity with checkpoint inhibitors. There's an approval in the HER2 positive subset of gastric cancer For pembroke plus HER2 targeting agent, that that may be a cancer indication where it would make sense To combine with an anti PD-one or other checkpoint inhibitor, and that's what I think we'll be considering.

Speaker 6

Terrific. Thanks very much for taking the questions and good luck.

Speaker 1

Thanks, Ryan.

Operator

Thank you. Your next question comes from Stephen Willey with Stifel. Please go ahead.

Speaker 7

Hi, guys. This is Tumi on for Steve. Can you guys hear me okay?

Speaker 1

We can hear you just fine. Thank you.

Speaker 7

Okay, great. Thank you. So I have two questions on my end, starting with the Q101 Plus pembrolizumab, the combination cohort, do you think you guys will pursue Specific target population moving forward like because you guys mentioned a lot about how this combination improves Low CPS, low CPS score 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 targeting specific population? So that's related to Q101.

Speaker 7

And regarding Q1 of 'twenty, can you please provide a little more color on enrollment dynamics and maybe Possibly, additional comment on like how many pieces have been enrolled so far? And if possible, Maybe additional color on like data disclosure, data update at Citi. So that's all on my end. Thank you very much.

Speaker 1

Thank you. I think the first question had to do with stratifying with CPS scores.

Speaker 3

Yes, I can't, but I'm happy to take this. Thank you for these great questions. And so with regards to Q101 and pembrolizumab And the data that we're observing, right, where we have a really meaningful tripling of response rate In the CPS low population, also we have about 1.6 times increase in the CPS high population. So the way I think we're thinking about this, this is actually really a win win for any patients that are being treated in the first line setting with a check inhibitors such as pembrolizumab. So, if you actually look at the data on the low population, It's less than 1 in 5 patients that benefit or have a response.

Speaker 3

And so if we can push that up to 50%, That's fantastic for the patients. And then even in the CPS high population, we have a clear benefit Of improving the activity there. So I think where things stand now, pembrolizumab 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 Q102, the enrollment is in my experience been close to The fastest for a dose escalation Phase 1 advanced cancer study.

Speaker 3

And as I mentioned before, this is really borne out of the The remarkable enthusiasm of the investigators and I think also it underscores the large unmet need of patients with Advanced disease in these four indications. Regarding the numbers of patients, I think We anticipate presenting the initial data on approximately 20 patients or more at SITC in November. And the data that we'll be presenting at that time is the initial observations on the safety and tolerability Of Q102 monotherapy, we have already and we'll fill out more some preliminary pharmacokinetic qualitative 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 are going to help us I do the qualitative analyses and we hope to have some of that data to share at SITC as well.

Speaker 7

Thank you very much. Thank

Operator

you. Thank Your next question comes from Peter Allard with Oppenheimer. Please go ahead.

Speaker 3

Hey, guys. It's Trevor. Hi, Peter. Thanks for taking the question. Excited to see the SITC updates.

Speaker 3

So looking ahead to 2024, can you guys discuss some of the additional data that we might see throughout the year there?

Speaker 1

Yes. On 2024, obviously, we'll have resolution from our FDA discussions with the What indication, what line, front line, third line, both, by in 2024, we should have Also the decision of whether we're partnering 101 and with whom, what structure. 102, as Matteo just articulated, we have a very enviable position. We have multiple cancers. We're Seeing early activity and dose escalation, just to reiterate what Matteo conveyed during the call, we're seeing activity at the 1 mg and 2 mg Dose level.

Speaker 1

So we also have the scans for 48 will be providing at SITC. So going into 2024, it's going to be a pretty exciting year just from a standpoint Prioritizing, obviously in this current financial climate, we have resource requirements that we're going To address, so most likely through strategic, we also have data from 401 that is emerging. We'll have clarity by end of Going into 2024, we consider that to be a really important transitional year for us. So I 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 expansion decisions. Okay.

Speaker 1

Yes, appreciate it.

Operator

Thank you. At this time, there are no further questions. Please proceed with your closing remarks.

Speaker 1

Yes. I want to thank everyone for your time and interest in our continued progress. We're clearly making very good Steady progress as we move forward and we're looking forward to SITC and providing you with further updates as we continue developing for the remainder of the year. Wish everyone a pleasant remainder of the week. And again, thank you for your interest and take care.

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Earnings Conference Call
Cue Biopharma Q2 2023
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