Cue Biopharma Q4 2023 Earnings Call Transcript

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Provided by Quartr
April 8, 2024

There are 8 speakers on the call.

Operator

Greetings and welcome to the Q Biopharma Investor Update Call.

Operator

At this time, all participants are in listen only mode.

Speaker 1

A question and answer

Operator

session will follow the presentation. As a reminder, this conference is being recorded. I would now like to turn the conference over to Dan Fasseri, Q Biopharma's Chief Executive Officer. You may begin now.

Speaker 2

All right. Thank you and good afternoon everyone. As a reminder, this presentation and discussion is being recorded and will be available on our website for the next 30 days. Also, please be aware that the slides accompanying today's update may be advanced directly by those listening in on the call and we'll notify you on what slide we're on throughout this presentation. Joining me on today's call are Doctor.

Speaker 2

Anish Suri, our President and Chief Scientific Officer Doctor. Matteo Levissetti, our Chief Medical Officer and Carrie Anne Millar, our Chief Financial Officer. As shown on Slide 2, this presentation and overview may contain some forward looking statements and any forward looking statement made during this call represents the company's views only as of today, April 8, 2024. Okay. As shown on Slide 3, I'm going to begin with a summary overview of the broad reach of our therapeutic platform and review our positioning and key corporate objectives going forward.

Speaker 2

Anish will then provide an overarching summary of our platform approach and in support of developments, reinforcing our positioning as a leading solution provider and the development of selective immunotherapeutic biologics to address pressing unmet medical needs in both oncology and autoimmune disease. Matteo is then going to review and update of our promising and evolving oncology clinical data sets as well as provide a summary synopsis of our recent and productive Type B meeting with the FDA to align on registration paths forward for Q101. Anish will then return to provide an overview of highly promising data from our preclinical autoimmune programs with the potential of having a profound impact on the treatment of autoimmune disease. Carrie will then join the call and provide a brief update on our financials, and I'll return for closing remarks prior to opening the call to questions. Okay.

Speaker 2

So to summarize, the data generated to date from our ongoing clinical trials with Q101 and Q102, as well as our preclinical programs, continue to move us closer to achieving our core mission and vision of becoming a leading solution provider for realizing the tremendous therapeutic potential of selective modulation of the patient's immune system in the treatment of cancer and autoimmune disease. As shown here on slide number 4, we aim to achieve this by engineering biologics that translate nature's cues that is signals from nature that are built into our biology and to breakthrough immunotherapies. We have continued to progress forward with positive and evident results in our ongoing clinical trials, demonstrating and further bolstering the therapeutic potential of our immunostat platform for treating cancer. To date, the strengthening data from our ongoing clinical Phase 1a and b trial with Q101 for HPV positive head and neck cancer and Q102 for treating the numerous types of WT1 or Wilms Tumor 1 over expressing cancers strengthens our belief that we've developed a therapeutically effective and well tolerated approach for the selective modulation of cancer relevant T cells. Importantly, we recently received guidance in alignment with the FDA through an end of Phase 1 Type B meeting for the continued development of Q101 towards registration trial.

Speaker 2

Matteo will provide further details on this prospect momentarily. We've also made significant prospect with our preclinical autoimmune programs, principally Q401 in collaboration with our partner Ono Pharmaceutical and the effect of these novel approaches. Anish is going to cover these in more detail momentarily. Through these ongoing developments, both in oncology as well as autoimmune disease, we're well positioned for strategic alignment with third parties for further increasing and enhancing our capacity to develop our highly promising and potentially transformative therapeutics. We've made significant progress towards our goal of consummating a transformational transaction that would enable greater capacity and enhanced productivity.

Speaker 2

I'm going to come back at the end of this call and further elaborate on this topic in the closing remarks. I'll now turn the call over to Anish, who will describe our core competitive positioning and the strategic implications of our approach for treating both oncology as well as autoimmune disease. Anish?

Speaker 3

Thanks, Dan. Good afternoon to all listening in on today's call. I'll provide a brief summary of our platform and the significant potential of our therapeutics for treating cancers and autoimmune diseases. As shown on Slide 5, immune balance is a key central pillar of human health and deviation from the state underscores diseases such as cancer and autoimmunity. Hence an effective therapeutic strategy for resetting immune balance should focus on selective modulation of disease relevant immune cells while avoiding broad perturbations of the immune system.

Speaker 3

Most importantly, this approach allows us to maximize efficacy while preserving patient safety. Slide 6 provides an introduction to our immunostat platform for resetting immune balance via selective modulation of disease relevant immune cells. The core framework of an immunostat builds upon nature's selectivity for T cell engagement and activation. Disease specific T cells express singular T cell receptors or TCRs that engage the stabilized peptide HLA molecules or PHLAs in an immunostat. Only those engaged T cells can then receive a disease modifying secondary on other T cells that are not relevant to the disease of interest.

Speaker 3

Importantly, the ImmunoStat framework was engineered to be highly flexible and modular, enabling us to deploy the same or similar core functional elements for diverse therapeutic approaches. For example, in the case of oncology, immunostats can selectively engage and activate tumor specific T cells while avoiding systemic immune activation. In contrast for autoimmune diseases, immunostats can selectively down modulate autoreactive T cells while avoiding broad immunosuppression. The next slide, Slide 7 highlights the pipeline of assets that we have developed for restoration of immune balance. In oncology, we have clinically validated Q100 series that selectively delivers the potent cytokine IL-two along with a TCR activating signal to preferentially activate tumor specific T cells while sparing all other irrelevant T cells.

Speaker 3

This selective stimulation allows for the generation of a therapeutic index for IL-two, which has alluded many others trying to develop IL-two based cancer therapies. In over 100 patients dosed, we have demonstrated a substantial increase in efficacy with favorable tolerability. For our lead clinical candidate Q101 in recurrent metastatic head and neck cancer, we have recently concluded a meeting with the FDA aligning on a registration path, which will be further elaborated upon momentarily by Mattel.

Speaker 4

With our

Speaker 3

next clinical candidate Q102 that targets Wilms Tumor 1 or WT1, we have completed the Phase 1 monotherapy dose escalation in patients with gastric, ovarian, colorectal and pancreatic cancers and have noted evidence of antitumor activity and disease control in multiple patients. Matthieu will describe this efficacy data in detail along with the plans for our registrational path forward with Q101. On the autoimmune front, as shown here, we have developed 2 novel and highly promising approaches for restoring immune balance. Q-four zero one is a novel bispecific composed of an attenuated IL-two and TGF beta that together can stimulate the generation and expansion of regulatory T cells. Regulatory T cells or Tregs possess the ability to dampen and control auto reactive lymphocytes, which are responsible for inducing tissue damage in autoimmune disease.

Speaker 3

Hence, in this regard, Tregs are the master regulators of maintaining immune homeostasis in health. Q401 is currently partnered with Ono Pharmaceuticals and this collaboration is moving forward at a strong pace with much productivity. In addition to Q4 1, we've also developed a Q500 series to enable T cell mediated depletion of B cells. We believe this biologic holds the promise for achieving CAR T like efficacy in autoimmune patients and is significantly differentiated from other competing approaches such as ADCC, pan T cell engagers or CAR T cell therapies. We will expand on both autoimmune programs in the later part of this presentation.

Speaker 3

With that background, I'll now turn the call over to Matteo to provide a detailed clinical update on the data and future plans. Matteo?

Speaker 4

Thanks, Anish. Good afternoon to everyone listening in on today's call. I'm particularly pleased to provide you with this summary update as we have achieved important developmental milestones with the recent clinical data and believe we have not only defined the registration path forward, but also demonstrated the opportunity of the Q100 series as a potential breakthrough improving patient outcomes across multiple cancers. The clinical data from the ongoing Q101 trial continues to neck cancer treated in combination with pembrolizumab and for heavily pretreated recurrent metastatic head and neck cancer patients treated with monotherapy. We recently had an end of Phase 1 Type B meeting with the FDA, where we received guidance and aligned on a path forward to a registration trial for Q101.

Speaker 4

To that end, we plan to conduct a randomized Phase 2 study of Q101 in combination with pembrolizumab compared with pembrolizumab alone as first line treatment of patients with recurrent metastatic HPV positive head and neck cancer. This trial design and the resulting data will provide a clear assessment of treatment effect along with confirmation of optimal dose for the Phase 3 registrational trial will increase overall confidence and probability of succeeding with the registrational trial. We believe this approach is the optimal means of generating the highest probability of success in the most cost effective and direct manner. We intend to pursue this registrational approach with Q1 101 in the first line setting in combination with KEYTRUDA as this setting represents a significantly larger market and we believe due to the complementary mechanism of action between Q101 and KEYTRUDA, the patient impact and durability would likely also further reduce the patient population available in the second line setting over time. It also represents a straight path forward to move upstream in the treatment paradigm, extending market reach potential into the adjuvant setting, which represents the largest market opportunities.

Speaker 4

As shown on Slide 9, data from the ongoing clinical trials with Q101 as monotherapy and in combination with pembrolizumab have provided clinical proof of concept to validation and de risking of our immunostat platform. The latest data generated to date in 2024 continues to bolster prior observations, further enhancing our confidence in Q101 as a potential therapeutic to improve outcomes for patients battling HBV positive head and neck cancer. As previously and consistently stated, we believe Q101's unique mechanism of action as evidenced by the data generated to date enables effective and tolerated dosing and selective expansion of the targeted tumor specific T cells. We continue to observe prolonged survival in patients with advanced recurrent metastatic head and neck cancer treated with Q101 monotherapy. Notably, as previously presented, the median overall survival of patients treated in the second line and beyond at the 4 milligram per kilogram monotherapy expansion dose is currently greater than 20 months, which compares favorably to the historical median overall survival of approximately 8 months observed in the second line trials of nivolumab and pembrolizumab.

Speaker 4

We believe this enhanced survival is due to the repeated stimulation and expansion of tumor specific T cells given Q101's mechanism of action, especially in the tumor microenvironment. As shown momentarily, the overall response rate in median progression free survival observed in first line patients treated with Q101 in combination with pembrolizumab represents a greater than doubling of the overall response rate and progression free survival compared to historical rates with pembrolizumab monotherapy. Enrollment in the neoadjuvant trial is progressing well and preliminary observations support expansion of E7 specific antitumor T cells and increases in NK cells within the tumor microenvironment. These findings are consistent with the pharmacodynamic changes observed in the peripheral blood of patients treated with Q101 as previously reported. We believe these observations in addition to the clinical efficacy observed in the recurrent metastatic setting support a development strategy of moving further upstream into earlier lines of therapy, such as the adjuvant setting where a larger number of patients may benefit.

Speaker 4

Pembrolizumab is approved as the standard of care treatment of first line patients with recurrent metastatic head and neck cancer that have tumors with CPS scores of greater than or equal to 1%. CPS is a measure of PD L1 expression based on a response rate of 19% observed in the KEYNOTE-forty eight study. Following combination treatment with Q101, the overall response rate of 46% as shown on Slide 10 observed in patients with CPS greater than or equal to 1 treated to date represents a greater than doubling compared to the historical overall response rate of 19% observed with pembrolizumab monotherapy. As shown on the waterfall plot, we have observed significant tumor reductions across many patients, including confirmed partial responses in 10 patients and a confirmed response in one patient. Importantly, 11 patients remain on treatment, including 3 with stable disease that exhibit reductions in their target lesions.

Speaker 4

Notably, for patients with low CPS scores, an overall response rate of 50% was observed with Q101 in pembrolizumab, which represents a greater than tripling of the historical overall response rate of approximately 15% observed with pembrolizumab alone. In totality, our data suggests that not only does Q101 appear to demonstrably enhance the response rate of PD-one inhibition, but also 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. E. Values of 1 to 19 represent approximately 50% of all patients that are CPS positive and eligible for treatment with checkpoint inhibitor in the frontline setting.

Speaker 4

The responses observed in these patients have been durable, an observation that is reflected in the improved progression free survival, which is shown on the next slide, Slide 11. Of note, the Kaplan Meier estimate of the median progression free survival for patients treated with Q1 101 in combination with pembrolizumab, as shown on the left is currently 8.3 months, which compares very favorably to the historical median progression free survival of 3.2 months observed with pembrolizumab monotherapy in the KEYNOTE-forty eight trial as shown on the right. Furthermore, 20 of the 25 patients treated to date, the 4 mg per kg expansion dose in the ongoing Q101 combination trial remain alive as of the last follow-up for each patient. This portends well for the median overall survival as it matures throughout the year. As shown in the panel on the left of Slide 12, we have observed robust expansion of tumor specific HBV E7 specific T cells in the peripheral blood of patients treated with Q101.

Speaker 4

As shown on the graph on the right, we have observed an approximate 100% decrease in cell free HPV DNA, which is an increasingly recognized biomarker of disease burden in all patients that have experienced objective responses that were tested to date, further supporting the magnitude of their responses. Reductions in cell free HBV DNA of this magnitude have also been observed in multiple patients with durable stable disease as defined by RECIST. The data from the Q10101 trial provided the substrate for a productive Type B meeting with FDA, which occurred earlier this year. In the course of this meeting, we aligned with FDA on a path to support a future Q101 plus pembrolizumab registrational trial, including guidance on the design of a small Phase 2 trial to confirm the Q1 101 dose used for a subsequent registrational trial consistent with the Project OPTIMIS directive. An overview of the planned Phase 2 trial is displayed on Slide 13.

Speaker 4

Treatment naive first line with recurrent metastatic H3B positive head and neck cancer will be randomized to 1 of 2 Q101 doses in combination with pembrolizumab or pembrolizumab alone. Overall response rate will be the primary endpoint with others including PFS and OS as secondary endpoints. The primary analysis of overall response is anticipated to occur approximately 24 months after the first patient is enrolled. As outlined on Slide 14, the clinical benefit observed with We believe this Phase 2 trial design and the resulting data will provide a clear estimation of treatment effect, confirmation of the dose to be tested in Phase 3 and increase the overall probability of success for the registrational trial. As demonstrated with the Q102 program, which I will now discuss, we believe the data from Q101 has provided a derisking and mechanistic validation for additional biologics from the IL-two based Q100 series.

Speaker 4

As a reminder, shown on Slide 16, Q102 and Q101 shared 99% amino acid sequence identity. This enabled us to significantly decrease the development time and cost of Q102 as we were not required by the FDA to repeat IND enabling toxicology studies for Q102 and we were also able to initiate the Phase 1 dose escalation study at 1 milligram per kilogram, a dose at which we observed clear signs of biologic activity with Q101. We have now completed the dose escalation portion of the 1 onetwo study without observing any dose limiting toxicities and are currently enrolling patients in all four indications in the expansion phase of the trial. As shown on Slide 17, gastric, ovarian, pancreatic and colon cancer represent areas of high unmet need. Note that these numbers are greater than a collective of 200,000 patients with recurrent metastatic disease in need of therapeutic options.

Speaker 4

In addition, an almost equal number of patients with other WT1 positive cancers are eligible to benefit from Q1-two therapy in the future. Emerging pharmacodynamic data from blood samples of patients treated with Q102 is shown on Slide 18. As seen here on the left, and consistent with our preclinical data sets and our experience with Q1-one hundred and one, selective and robust expansion of WT1 specific T cells has been noted among the patients treated with Q102, with 2 representative examples shown here. Expansion of these tumor specific T cells is expected to enhance antitumor immunity with the potential to drive tumor reductions as shown on the right. A patient with gastric cancer that progressed on 3 prior lines of therapy, including a checkpoint inhibitor, has experienced a decrease in the sum of 3 target lesions of -34% at week 36.

Speaker 4

Another example of reduction in tumor burden this time in a patient with recurrent metastatic ovarian cancer is shown on the right. Unfortunately, these two patients were found to have new lesions on subsequent scans and have now come off treatment. Also of note, a pancreatic cancer patient treated on the study has benefited through maintaining stable disease for greater than 8 months, which is remarkable in the setting of this devastatingly aggressive tumor type. Given the encouraging signals of clinical activity, including multiple patients with stable disease observed across all four indications and the enthusiasm of the investigators, the protocol was amended to expand into all four indications. The study is actively enrolling patients in all four of these indications.

Speaker 4

Patient screening and enrollment rate continue to go exceedingly well, underscoring investigator enthusiasm and the need for effective therapies in WT1 expressing cancers. As demonstrated on Slide 19, it's important to note that while checkpoint inhibitors have had a major positive impact on changing the therapeutic options for patients, there remains a substantial need for improvement. There have been significant persistent challenges in realizing the fullest potential of immunotherapies. While many therapeutic modalities and combination approaches for immune modulation are being pursued, significant challenges exist with regards to suboptimal safety, tolerability and efficacy to enable broad patient reach. We believe solution providers to these challenge will emerge as best in class market leaders defining the paths forward for more effective therapies, both as standalone treatment options as well as combination approaches, for example, with checkpoint inhibitors.

Speaker 4

As just conveyed, the ability of Q101 to selectively expand and activate targeted tumor specific T cells, complements the mechanism of checkpoint inhibition, thus expanding patient reach and enhancing therapeutic benefit as demonstrated in this chart. We believe our platform has the potential to significantly expand patient reach by increasing the number of patients that benefit and enhancing the magnitude of that therapeutic benefit. In short, we believe our platform represents a major breakthrough towards realizing the full potential of immunotherapy. We are further encouraged by the early observations of Q102 monotherapy, antitumor activity across multiple indications where checkpoint inhibitors have been largely ineffective. We look forward to presenting additional data on both programs at ASCO in June.

Speaker 4

I will now turn the call over to Anish. Anish?

Speaker 3

Thanks, Matteo. Let me take a few minutes to update on the notable progress with our platform for autoimmune diseases, starting with Q4-one and regulatory T cells as indicated on Slide 20. Slide 21 describes the design and rationale for Q4 1 as an attractive approach to generate a new and differentiated class of regulatory T cells or Tregs. As mentioned previously, Q4-one is a bispecific molecule containing attenuated forms of IL-two and TGF beta, which are the 2 known signals that can convert peripheral T cells into regulatory T cells, also known as induced Tregs or I Tregs. In addition, Q4-one also strongly expands existing natural Tregs.

Speaker 3

This program has been a very productive collaboration with Ono Pharmaceuticals, wherein Ono is supporting all of our ongoing preclinical work to identify an optimized clinical lead compound, which we are on track to accomplish in the second half of twenty twenty four. The next slide, Slide 22 highlights the unique and differentiated mechanism of action of Q4-one over other CD25 biased IL-two mutants for expansion of existing Tregs. As shown here, Q4-one can expand pre existing regulatory T cells and convert naive CD4 positive T cells into new Tregs, thereby enhancing the quantitative population and the qualitative features of Tregs control the pathogenic cellular reactions in autoimmune patients. Slide 23 provides examples of the potent activity of Q4-one in the conversion and generation of stable Treg cells. As shown in the left panel, conversion and expansion of human CD4 T cells to Tregs only occurs when the IL-two and TGF beta signals are delivered via Q4-one.

Speaker 3

Either signal alone does not result in Treg conversion and Q401 represents the 1st singular biologic capable of delivering both signals simultaneously. In the right panel is an in vivo study demonstrating efficacy of Q4 1 in an animal model of autoimmune gastritis. This is a model developed by Doctor. Rich DePaolo at St. Louis University, wherein a short treatment with Q4-one results in a long lasting protection from gastritis as shown by the histopathological analysis and disease scores.

Speaker 3

We believe this mechanism of action of Q4 1, including the demonstration of long lasting efficacy after just a short duration of treatment will apply to many other autoimmune diseases. Let's move on to Slide 24 that introduces a new series of immunostats, termed the Q500 series that we have developed with the goal of achieving deep B cell depletion via T cell mediated approach. As shown on the next slide, Slide 25, recent data sets from small clinical studies have demonstrated remarkable efficacy in autoimmune patients treated with CAR T cells directed against CE19 to deplete B cells. In many cases, long term ongoing clinical remissions have been noted in patients with lupus and myositis with no concurrent immunosuppressive regimens, which could be early signals of functional cures. This curative potential via immune reset is what propelled us to start working on the Q500 series, which enables T cell mediated B cell killing, akin to what CAR Ts do, except with an off the shelf biologic.

Speaker 3

This concept is best shown on the next slide, Slide 26. The Q500 series builds upon the clinical derisking accomplished with the Q100 series. The constant is the presence of a bivalent peptide HLA molecule that selectively engages TCRs of selected T cells. In the case of the Q500 series, the peptide presented by the HLA is a well characterized virus epitope recognized by virus specific memory T cells present in high frequencies in all of us. Examples of such virus epitopes would include CMV, EVV, SARS CoV-two, etcetera.

Speaker 3

In addition, the Q500 molecule also contains SCFEs directed against B cell cell surface molecules such as CD19. This configuration allows for Q500 molecules to bind target B cells and make them appear as virally infected cells that can be recognized and destroyed by our protective antiviral memory T cell This novel mechanism of action is depicted in the left panel on the next slide, Slide 27. This mechanism of natural target recognition via TCRs is of similar sensitivity, if not higher, compared to how a CAR T cell recognizes its target via the CAR domain. On the right side of the slide is an example of a Q500 molecule enabling cytomegalovirus specific T cells, CMV T cells to kill primary human B cells. It is well known that CMV specific T cells are a significant composition of the protective antiviral T cell repertoire and are present in large fraction of the population.

Speaker 3

As shown here, B cell killing is specific to the engagement of CMV specific T cells. In other words, a Q500 molecule harboring an HIV peptide does not mediate B cell killing since the HIV specific T cells are not present in circulation. So the selective harnessing and redirection of the protective antiviral T cells to kill targets creates a very attractive opportunity for Q500 series immunostats. This is particularly exemplified in the next slide, Slide 28, which highlights the market opportunity for a broad therapeutic pipeline with a single product. The therapeutic application span from multiple autoimmune diseases where pathogenic B cells play a role to additional applications in transplantation and allergic inflammation.

Speaker 3

The Q500 series could also be effectively applied for the treatment of B cell malignancies in the oncology therapeutic area. The next slide, Slide 29 briefly summarizes the superior differentiation of the mechanism of action of Q500 over other competing modalities for B cell depletion, including ADCC, CAR T cellular therapy and pan T cell engages. We now recognize that ADCC mechanisms result in incomplete depletion of B cells, primarily due to variable expression of the target antigen such as CD19. Low target expression allows for escape of B cells from ADCC primarily mediated by NK cells. Furthermore, Fc receptor polymorphisms dictate high versus low ADCC effector genotypes.

Speaker 3

In the case of CAR T approaches, complex manufacturing and supply chains remain a challenge for broad access. In addition, patient conditioning regimens, inpatient administration and safety risks, including CRS and neurotoxicity continue to pose challenges for CAR T therapies. And T cell engagers that activate T cells via anti CD3 or anti CD28 cross linking are also not favorable for autoimmune applications. These modalities activate all T cells indiscriminately resulting in CRS and other toxicities, Hence are suitable hence are unsuitable for autoimmune patients. In addition, they pose the very real threat of further activating and propagating auto reactive T cells that may exacerbate the underlying autoimmune disease.

Speaker 3

In contrast to these modalities, the Q500 series offers an elegant potential solution for selectively exploiting the long lasting antiviral memory T cells to drive B cell depletion. This off the shelf approach therefore offers the potential to achieve CAR T like efficacy while avoiding the pitfalls associated with cell therapy modalities. With that overview on both Q401 and Q500 and their applications in autoimmune disorders, I'll turn the call to Keri to review the financial details. Keri?

Speaker 5

Thanks, Anish. Turning to Slide 30, I'd like to provide a brief update on our financial results for the 3 months and full year ended December 31, 2023. For the 3 months ended December 31, 2023, the company reported collaboration revenue of approximately $1,800,000 as compared to 150,000 for the same period in 2022. Revenue in the Q4 was primarily due to work related to the collaboration and option agreement with Oono Pharmaceuticals for Q4-one, which was executed in the Q1 of 2023. Research and development expenses were $10,900,000 $11,300,000 for the 3 months ended December 31, 2023 and 2022 respectively.

Speaker 5

The decrease was primarily due to drug substance manufacturing projects Q101 and Q102 that were completed in 2022. General and administrative expenses were $4,600,000 3,700,000 for the 3 months ended December 31, 2023 and 2022 respectively. The increase was primarily due to an increase in professional and consulting fees during this time. For the years ended December 31, 2023, 2022, the company reported collaboration revenue of approximately $5,500,000 $1,200,000 respectively. The increase was due to the revenue earned from our strategic collaboration agreement with Ono Pharmaceuticals.

Speaker 5

Research and development expenses were $40,800,000 38,600,000 for the years ended December 31, 2023, 2022, respectively. The increase was due primarily to clinical development costs and research and laboratory which were partially offset by decreases in employee costs and rent expense. General and administrative expenses remained relatively flat $16,700,000 $16,200,000 for the years ended December 31, 2023 and 2022 respectively. And as of December 31, 2023, the company had approximately $48,500,000 in cash and cash equivalents, $34,400,000 in working capital and 47,200,000 common shares outstanding. We expect our current cash and cash equivalents to fund operations into the Q1 of 2025.

Speaker 5

I'll now turn the call back over to Dan for closing remarks. Dan?

Speaker 2

Yes. Thanks, Carrie. As you've just heard, our growing body of data in both clinical oncology and with preclinical autoimmune disease continues to support and reinforce premise and firm belief that CUE's platform holds tremendous potential to transform immunotherapy for both cancer and autoimmune disease by selectively modulating the patient's immune system in a highly targeted and tolerated manner. We believe the data we've generated to date in oncology with Q101 and Q102 have clearly demonstrated the selective and targeted activation and expansion of cancer relevant CD8 positive T cells in a qualitatively distinctive manner. Furthermore, these data demonstrate clear signs of durable anti tumor activity and mechanistic complementarity with checkpoint inhibitors.

Speaker 2

Let me remind everyone listening in that the patients we're treating are refractory, that is resistant to prior therapy and metastatic, That is their cancer has not only recurred, but has also spread to multiple locations after primary treatment. As a result, these patients have a very poor overall prognosis. And importantly, both Q101 and Q102 have demonstrated the potential of stimulating the patient's immune system to recognize the tumors growing in their bodies as foreign marshalling an attack. Furthermore, the clinical observations to date support the putative mechanism of action for Q101 and by implication Q102 as well as the entire IL-two based Q100 series, mechanistically complementing immune checkpoint inhibitors such as KEYTRUDA. We see this compilation of data as a key strategic advantage for expanding patient reach and therapeutic benefit of checkpoint inhibitors, positioning us well for strategic alignment with potential partners to enhance their competitive positioning.

Speaker 2

As conveyed in Slide 31, we are well positioned for value inflection milestones over the coming year, namely with Q101 moving into a randomized Phase 2 study with the intention of providing confirmation of enhanced efficacy that we've seen in the prior studies that we've presented on in the 1a and 1b, which is our Q101 plus checkpoint inhibitor versus the checkpoint inhibitor standard of care alone. We expect interim analysis at 14 months and the overall response rate and median progression free survival analysis between 22 24 months, both of which underscore breakthrough potential with Q101 plus checkpoint inhibitor to establish a new standard of care for these frontline refractory metastatic head and neck squamous cell carcinoma patients, but also has far reaching implications for our immunostat platform application in solid tumors per se by expanding patient reach and enhancing clinical benefits enhancing clinical benefits of checkpoint inhibitors and to a broad range of cancers. Successful readout in the randomized Phase 2 would place Cube in a position of leverage and strength a partner of choice for checkpoint inhibitor franchises. Furthermore, Q102 patient expansion positions combinations with checkpoint inhibitors in large indication segments where checkpoint inhibitors have historically failed to achieve approval.

Speaker 2

We have also generated a body of data highly supportive of the mechanistic advantages and disruptive potential of our autoimmune programs, namely Q4-one for Treg induction, currently partnered with Ono, of which we have retained an option for a 50% interest in the U. Market with 2 near term milestones potentially being realized and Q501 for B cell ablation with the potential to displace CAR T with a biologic for B cell driven autoimmune disease such as lupus. As conveyed in the next slide number 32, we've positioned CUE well for strategic and competitive positioning with the establishment of clinical proof of concept with our 2 lead oncology programs whereby our clinical data generated to date have the potential to shift the treatment paradigm and that we've demonstrated significant and meaningful increase in the overall response rate, median progression free survival and overall survival, resulting in the promise that we have the potential to revitalize checkpoint inhibitor sector and enhance market reach and have also demonstrated platform modularity and scalability. Through this modularity and scalability, we have multiple applications of our novel platform having the potential to address some of the largest pharmaceutical markets in the U. S.

Speaker 2

And global application for solid tumors and autoimmune disease indications. Through these ongoing developments, we have made significant progress over the past quarter with our corporate development and business development initiatives. We are presently engaging in ongoing strategic discourse with multiple prospective strategic partners. Based on continued development through these ongoing discussions, we're highly confident we'll be successful consummating 1 or more of these transactions in a timely manner, enabling strategic alignment, enhancing our capacity and enabling access to requisite capital towards the realization of our corporate mission. On that, I'd like to we would like to extend our sincere thanks and appreciation to our committed shareholders, passionate employees, Board of Directors, Scientific Advisory Board, clinical investigators and our collaboration partners for their continued support, guidance and trust.

Speaker 2

And most importantly, we extend our profound appreciation and respect to the patients and their families who have participated in our clinical trials, enabling us to gain insights and knowledge essential for continued progress in the fight against cancer and other debilitating diseases. With that, I'd like to now turn the call back over to the operator to open up for questions. Operator?

Operator

Thank you. Ladies and gentlemen, we will now conduct the question and answer session. Your first question comes from Maury Raycroft from Jefferies. Your line is now open.

Speaker 6

Hi, congrats on the progress and thanks for taking my questions. I was going to ask about the randomized Phase 2 combo study. Can you talk about how many patients you anticipate you'll need in each arm? And if you're successful on that 1st interim, on overall response rate, would that allow you to advance into a registrational Phase 3?

Speaker 2

Sure. Matteo, do you want to take that question? Thanks, Mark.

Speaker 4

Yes, certainly. So the patient sample size for the entire trial is planned to be less than 100 patients, so approximately 25 patients per arm. And then regarding the first interim analysis, given that this is a randomized trial, we'll have a data safety monitoring board that will look at the results at that first interim and provide a recommendation to continue the trial per protocol if everything looks good and it's really the final analysis at 24 months, 22 to 24 months that would serve as the substrate to proceed into a registrational trial, although a fair bit of trial startup could be done once the interim analysis, the first one provides a positive recommendation to move forward.

Speaker 6

Got it. That's helpful. And, Dan, you talked about potential partnering. Can you clarify what stage you would look to potentially partner? Would it be as you're running the Phase 2 or before the Phase 3?

Speaker 6

And then what could potential partnership look like from a development and economic standpoint?

Speaker 2

Sure. Very important question and Maury, and as you know, it's a dynamic question in that there's no one answer to that. It's really looking at a number of factors that we will consider. So we're presently in discussions, let's just say, with multiple parties across the various asset classes we have. So pertaining to Q101, Q102, I think the key there is identifying an appropriate party with the sort of requisite insight on the disease indication that can sort of enhance our own capacity and provide the requisite support.

Speaker 2

We certainly don't want to be giving up on the economics too much of the promise of those assets. So it's really going to be based on our continued involvement, particularly in the randomized Phase 2, the type of support we would have in the economics downstream. So we're in discussions with various parties and we'll be looking at different economic structures to make that decision. And ultimately, it's a Board decision. So we've been in dialogue with the Board on an ongoing basis and ultimately, we will present various scenarios and make the decision accordingly.

Speaker 2

And regarding autoimmune, same type of sort of dynamic analysis. I would just use Ono as an example. The structure of that partnership was very favorable. They've actually been an outstanding partner with an early asset. They're basically subsidizing the development.

Speaker 2

We have a very interactive partnership, but we've retained a 50% upside option upon selection of the clinical candidate when we begin IND enabling studies. And that allows us to preserve sort of optimal upside for our shareholders as well. The sort of risk capital particularly in the early stages is being subsidized. So I hope that answers your question, but we'll be looking at it in a dynamic manner based on the various options we have in front of us.

Speaker 6

Got it. That's helpful. And for the 501 program, just wondering if you can talk more about where you're at with preclinical development for that program. And you talked a little bit about potentially partnering this one too. Would this be from the 500 series, would it be one asset or would it be part of this 500 series platform?

Speaker 6

How would you think about that?

Speaker 3

Yes, Maurice. So this is Anish. What we have so far is clear evidence that we've been able to make the scaffold and is biologically active, as you can see. We've tested this across a number of different memory T cell specificities, so CMV being one which is highly present in a majority of us, but also SARS CoV-two at this point in time, there's a very conserved epitope from the spike protein that virtually all of us today in the world should have SARS specific T cells, whether it's by vaccination or natural infection. So that provides a great substrate to essentially use this nature's pandemic to redirect it to something good, which is destroying these pathogenic B cells and down the road.

Speaker 3

We started initially with CD19, Maury, but you can think about the concept actually extending beyond just B cells to other pathogenic cell types. I also think and we think very strongly that this can also extend very nicely into the oncology setting, particularly solid tumors where you just swap out the SCF V of the B cells to a cell surface tumor antigen. I mean think about PSMA, think about TROP-two, think about HER2, etcetera. So I think there's a vast potential for this. As we started talking, the additional interest has actually been an extraordinary amount of inbound interest from companies and parties that have been interested in really getting CAR T like efficacy in what was recently demonstrated in these small studies in autoimmunity.

Speaker 3

So that is the starting position and we've made good progress. The scaffold actually is derisked very much by the 100 series as I that's why I sort of stress that. The core component remains the same. It's a bivalent peptide HLA and obviously has no IL-two instead of that the mod is an anchoring SCFE. So again, there's a lot of good learnings from the 100 series, 101, 102 that sort of beneficially impact the 500 series.

Speaker 6

Got it. That's really helpful. Thanks for taking

Speaker 7

my questions.

Speaker 4

Thank you. Thank you.

Operator

Your next question comes from Stephen Willey from Stifel. Your line is now open.

Speaker 7

Yes, good afternoon. Thanks for taking the questions and apologize for the background noise. But maybe just a couple more Phase II questions. Can you just maybe speak to the 2nd KEY101 dose that you're contemplating including into the randomized Phase 2? And then can you also speak as to kind of what triggers the interim analysis?

Speaker 7

Is that just having a given number of patients out beyond some specific duration of follow-up? And then I just have another question.

Speaker 4

Okay. Materially So I can thank you. Very good questions. And so the doses that we anticipate examining are certainly the 4 milligram per kilogram dose that we've really studied in 25 patients with now objective response rate of close to 50%. We haven't finalized the selection of the other dose.

Speaker 4

However, we have quite a bit of experience with 2 milligrams per kilogram as monotherapy, wherein that set of patients of 9 patients, we actually see a very pronounced extended survival. And then in the dose escalation at 2 mgs per kg with pembrolizumab, we also observed a very profound durable objective response. So I think the answer there will be 2 doses. Certainly, we believe at this point 4 mgs per kg and then very likely a 2 mg per kg dose where we've seen really very strong activity, as well. With regards to the triggering of the first interim analysis, it really will be determined when approximately 70% to 80% of patients have gotten through the cycle 5 scan, okay.

Speaker 4

So it's really a look to be sure that what we anticipate to observe or the SMB would observe, can make that assessment once, as I mentioned, 70% to 80% of patients have gotten to their cycle 5 scan. And we'd anticipate that based on what we've observed to date in the 1010 and one trial and the historical monotherapy rate that that would progress then to ultimately the final analysis, which again that will be a complete analysis of the dataset with all patients now having follow-up through cycle 5 to get to your primary overall response rate. That final analysis is very valuable because that yields data then that can be brought forward to start your Phase 3. And the way it's designed then allows also for follow-up with the supplemental analysis for PFS and OS, but we don't have to wait for that to hold up the initiation of the Phase 3 trial.

Speaker 7

Okay. I guess that's helpful. And can you maybe just talk a little bit about kind of the pushes and pulls that were under consideration as you thought about carving out kind of an independent randomized Phase 2 versus trying to do something more Phase 2, 3 adaptive seamless? And maybe in answering that you can speak to, I guess to what extent if any was this path forward kind of informed by some of these ongoing strategic discussions?

Speaker 4

So very good question. And certainly an option to further develop the combination is to go with a Phase twothree sort of seamless design. The first component of that and this has become I think quite common since Project Optimist has sort of gone into effect as a directive or mandate, is to have a lead in with the 2 doses to select your dose and then to go into the Phase 3 randomized portion. So, I think there's multiple components to considerations. The initiation of that Phase twothree is a larger endeavor and investment, I think, clearly.

Speaker 4

And the Phase 2 really offers the opportunity to generate data that confirms the dose to go into Phase 3. And therefore, the Phase 3 is simpler in design where there's no lead in, which is actually takes quite a bit of time, at least a year to do. And then also gives the opportunity to have, if you will, a confirmatory analysis that would increase one's confidence in being successful in ultimately the Phase 3 trial.

Speaker 7

Okay. And then maybe just one quick follow-up. Mateo, I was just wondering if you had any thoughts around the pembro survival number that was recently presented from the LEAP-ten trial. And just I know we're still a couple of years away from a registrational study, but even in the context of a Phase 2, how do you think that influences your expectation as to what that survival number might look like? Thanks.

Speaker 4

Yes. So I think well, it's a bit of a mystery to me. I don't know that I've heard or that I'm aware of a clear explanation. Also a surprise that the objective response rate was 27% as opposed to the historical rate of 19%. So that arm in the trial did appear to do better than anticipated.

Speaker 4

I think again, it then supports the value of doing a Phase 2 trial before engaging into a registrational Phase III with almost 5 to 10 times the investment to really just gain confidence that we're on track with regards to what we believe the combination treatment effect is to the current monotherapy effect. So I think I hope that addresses the question. I don't and again, when this was presented at the Head and Neck Conference in Arizona, there was quite a bit of a discussion with the Head and Neck Experts. And no one really seemed to have an explanation. But again, with regards to lenvatinib, I think there's ideas or conceptions that the sort of broad array of kinase coverage may have some negative effects on the whole immunotherapy response to the checkpoint inhibitor.

Speaker 4

But that's conjecture on my part. But again, I hope that addresses your question.

Speaker 7

It does. Thanks for taking the questions.

Operator

Your next question comes from Ren Benjamin from JMP. Your line is now open.

Speaker 1

Hey, good afternoon guys. Thanks for taking the questions and congrats on the progress. Thanks. Vijay, I think you mentioned that there was some data coming out at ASCO for both 101 and 102. Can you just give us a sense as to I mean, I think the 101 studies, it's largely just longer term follow-up.

Speaker 1

Correct me if I'm wrong there. And then 102, about how many patients worth of data and what kind of follow-up should we be expecting?

Speaker 4

Yes, certainly. So I can share here that we're actually delighted to have been selected for an oral presentation on our Q10101 dataset at ASCO in June. It will be, as you alluded to, a comprehensive analysis of all the data with longer follow-up. With regards to the Q102, which was also selected for presentation as a poster at ASCO, we anticipate now having data on approximately 35 patients or more with some follow-up as long as out to 8 months.

Speaker 1

Perfect. And then as just going back to the strategic sort of partnerships and things that you're evaluating, as you think about, I guess, the way to move forward, how are you thinking about potentially just wrapping up 101102 kind of in a nice typo and presenting that as a potential acquisition that provides a significant upfront that allows you to fund, let's say, the autoimmune programs, which investors are paying a lot more attention to. You're clearly seeing that in the cell therapy space as well. They seem to be very enamored by the autoimmune data. How do you take that kind of decision making versus trying to find a strategic that can move with you both 101102 while spending your own money moving that forward?

Speaker 2

Yes. Ben, this is Dan. Probing question and a really important one, particularly I think in the headwinds in the current capital markets in oncology. I think it's clearly a prudent question with, I think, strategic insight into the challenges in the oncology sector. So we are looking at that dynamic.

Speaker 2

It hasn't evaded our thinking that the timeframe and the capital requirement for increasing value for shareholders would probably be more in favor of autoimmune in the current capital markets, but we have much deeper, more mature data. So I think the key for oncology is to align with a company that has the capacity and competencies to get through a registrational path. And the objective for us would be to be able to retain as much upside for our shareholders. So the calculus that we're ultimately going to decide upon is how we address capital requirements, which are pretty deep in oncology for a registration path. And that was by the way, it's part of the rationale that Matteo articulated as to the decision to do a randomized Phase 2, with a very defined discrete number of patients, we can add a substantial amount of confidence and value.

Speaker 2

And I think that's also part of our analysis having to do with strategic alignment with parties. I think pharma companies are finding that structure to be very attractive, where the degree of confidence goes up dramatically if the randomized data repeats what we've seen in our Phase 1a and b. So it's a very important question and it is part of our overall analysis and ultimately the calculus that determines what path we choose.

Speaker 1

Got it. I guess one final question for me on the autoimmune side. On the one hand, I'm a little bit confused as to how T cells that are targeting CMV completely deplete kind of all the B cells that are there. I can imagine some proportion, but all of it maybe Anish can help me understand this a little bit better. And when might we see some preclinical data at any upcoming conferences this year?

Speaker 3

Yes, Ren. So the T cell mediated depletion is essentially pan B cell depletion simply because of CD19 anchoring that's on every B cell out at least in circulation. So when the immune stat binds to the B cell displaying the CMV peptide HLA, for the CMV T cell that's simply presenting it as a surrogate for a virally infected cell and the cell goes into the effector mechanism. One of the reasons we focus on the virus specific for this application, Ren, is because of their ability to rapidly respond the effective memory compartment and one that is not dependent much on co stimulation. So you can actually rapidly recall these.

Speaker 3

They're present in high frequencies in a large majority of the population. And importantly, they're not exhausted. We know that from a body of literature that we've now had for decades in terms of the longer lasting memory repertoire. So that those things together make for a really strong case for selective harnessing of what nature gave you as nature's sort of long lasting killer population. You could make it specific to a discrete B cell subset, if one chooses to and achieve selective B cell depletion and that would just mean that you would swap the marker from a CD19 targeting to something else.

Speaker 3

And so that optionality remains with us. But I think as a central early mechanistic proof of concept CD19 was attractive enough, particularly also since the CAR T data is with CD19 targeting and that looks pretty robust at least with the early metrics we've seen. So we are in the midst of generating actually a body of data. There's a large part of the organization is looking at this with a significant amount of intensity, likely thinking to aim for either an autoimmune meeting or some translation or immunity meeting to be able to sort of bring out these concepts a bit more. So hopefully, maybe try to find something either in the second half of the year or early next year to be able to talk more about this.

Speaker 1

Excellent. Thanks for taking the questions.

Speaker 5

Lester? Operator?

Speaker 2

This is Dan. I think we have lost the operator.

Speaker 5

Yes. I think we're having a technical difficulty.

Speaker 2

I'll do the operator. So

Speaker 5

There's one more person waiting in the question queue that we'll try to get on.

Speaker 2

Okay. We seem to not be able to resolve the technical issue with the operator. So Dan, with that, I think we will end the call. I want to thank everyone for listening in. We look forward to providing everyone with substantive updates as they become available over the coming quarter.

Speaker 2

And as Matteo stated, we have presentations at ASCO, looking forward to presenting that data and autoimmune data at the appropriate conferences coming up over the coming year. I want to thank everyone for your attention and have a pleasant afternoon and evening. Thank you very much. Take care.

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Earnings Conference Call
Cue Biopharma Q4 2023
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