Cue Biopharma, Inc.

Greetings, and welcome to the QBioPharma fourth quarter and full year 2022 earnings call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. If anyone were to require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to your host, Mr. Dan Passeri, Chief Executive Officer. Please go ahead.

Yeah, thank you, and good afternoon, everyone. As a reminder, this conference will be recorded and available on our website for the next 30 days. Also, as a reminder, those listening in, just be aware of the webcast. You need to advance the slides as you are listening, and we'll notify you which slide we're on at a given time. Joining me on today's call is Dr. Matteo Levesetti, our Chief Medical Officer, Dr. Ken Pienta, now in the role as Clinical Advisory Cue, Dr. Anish Suri, our President and Chief Scientific Officer, and Kerry Millar, our Chief Financial Officer. Also joining us briefly on today's call is Dr. Sarah Pei, Surgical Oncologist and Director of Translational Head and Neck Cancer Research at the Mass General Hospital. She's an investigator on our ongoing trial with Q101. We'll provide a brief perspective of clinical observations to date. In addition to Dr. Pienta, Dr. Pei has also recently become a clinical advisor to QBioPharma, helping to define our clinical strategies going forward. As shown here on slide two, this presentation and overview may contain some forward-looking statements, and any forward-looking statements made during this call represents the company's views as of today, March 21st, 2023. On the next slide, please, you'll see our agenda. for today's call. I just want to please note that on this slide, under the financial results, that's meant to read fourth quarter 2022, not third quarter. Apologies for that. We just noticed that before the call. Okay, I'll begin by providing an overview and status update of our current corporate positioning, and we'll describe our competitive advantage, which we believe places us in a differentiated strategic position of strength and opportunity despite the present challenges of the capital markets. We're also well positioned with capital into the second half of 24, and importantly, our platform has generated numerous programs at various stages of development, representing multiple partnering opportunities. As a reminder, we recently entered into a strategic partnership with Ono Pharmaceuticals for the development of Q401, which is our buy-specific regulatory T cell inducer and activator for potentially addressing a broad spectrum of autoimmune diseases. Importantly, this transaction was structured to provide us with requisite capital through program funding, thereby subsidizing the ongoing research and development costs with Q retaining a 50% co-development option for the U.S. market. So this was obviously a very balanced transaction for the company. Q101's clinical data continues to support the clinical validation and the corresponding reduction of risk for the entire IL-2-based Q100 series and importantly appears to provide us with defined options for potential registration paths. Both Q101 and Q102 currently in clinical development address significant unmet medical need across multiple cancer indications. Based on the clinical data generated to date, we believe we're now well positioned with our oncology portfolio to seek partnerships and transactions similarly structured to the ONO partnership to ensure we retain involvement and upside, optimal upside potential while addressing capital access for building out our promising pipeline of potentially breakthrough therapeutics. As seen in the next slide, that's slide number four, we believe our corporate positioning and competitive advantage are firmly established on solid foundational data. And Q101, as an exemplary of the Q100 series, represents a potential therapeutic breakthrough. To date, Q101 has demonstrated, as you'll see on this slide, monotherapy activity in late stage cancer patients. What's important here is this is single agent activity in patients that basically are refractory to various chemotherapies, but also checkpoint inhibitors. To date, we're observing significant increase, that is at least a doubling of the overall response rate in combination with checkpoint inhibition compared with historic monotherapy with checkpoint inhibitors. Favorable tolerability, we've dosed greater than 70 patients to date with no evidence of vascular leak syndrome or cytokine release syndrome. Antibody-based design gives us favorable cost of goods for manufacturability, and actually the drug to date has demonstrated astonishingly stable characteristics where stability has gone out to greater than 36 months. Significant regulatory advantages, we have fast track designation and both mono as well as combination. And importantly the FDA authorized Q102 IND based on the safety data from Q101, basically viewing Q101 as an analog with no requirement for IND-enabling toxicology and approval to start the trial at a higher dose, saving significant time and cost. Matteo will elaborate upon these observations momentarily. We view the cumulative data as supportive of our central premise, namely that the Immunistat platform, and more specifically the IL-2-based Q100 series, represents a therapeutic breakthrough by harnessing nature's specificity. That's through targeting the T cell receptor, or TCR, enabling the targeted delivery of cytokines, such as IL-2, to disease-relevant T cells. We believe this approach enables the achievement of a therapeutic index for IL-2 and other cytokines by avoiding the deleterious side effects of non-selective indiscriminate activity, often seen with other modalities. As a reminder, our platform modularity allows us also to deploy other modulatory co-stimulators beyond IL-2 based on the same principle. I'm now going to turn the call over to Matteo, and then he'll be followed by Ken and Sarah to generally describe the emerging clinical observations from our ongoing Q101 and Q102 trials. Anish will then provide a brief summary for our autoimmune programs, emphasizing the recent developments, including the Q401 partnership with ONO. Mateo?

Thanks, Dan. The clinical data from the ongoing Q10101 trial continues to demonstrate robust metrics of clinical benefit for heavily pretreated recurrent metastatic HPV-positive head and neck squamous cell carcinoma 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 five, data from the ongoing clinical trials with Q101 as monotherapy and in combination with pembrolizumab have provided clinical proof of concept and de-risking 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 for patients battling HPV-positive head and neck squamous cell carcinoma. 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, enabling selective expansion of targeted tumor-specific T cells directly in the patient's body. Recurrent metastatic HPV-positive head and neck cancer is a tough and curable 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 a subset of these patients, resulting in demonstrable anti-tumor effect. Furthermore, and importantly, we continue to observe an evolving pattern of 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. As shown on slide six, Q101 demonstrates well-behaved pharmacokinetics with low interpatient variability at the recommended phase two dose of four milligrams per kilogram. The exposure pattern is consistent throughout multiple cycles of treatment without any attenuation of PK parameters, supporting the premise that there is no evidence of clinically relevant immunogenicity. Regarding its pharmacodynamic, or PD, profile, Q101 treatment also results in a consistently observed sustained increase in natural killer cells, or NK cells, a positive attribute associated with an antitumor response, as NK cells are known to assist in tumor killing. Importantly, we observed only a modest and transient increase in regulatory T cells. Regarding the intended PD effect, i.e., 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 one week after administration of Q101. Paired and post-treatment biopsies demonstrate an increase in tumor-infiltrating T cells and associated tumor necrosis. In addition to the favorable PK and PD just described in patients with advanced HPV positive head and neck cancer are experiencing intriguing patterns of clinical benefit. Three examples are shown on slide seven. Patient A experienced a durable partial response with an approximate 60% reduction in tumor burden evident at six weeks after two cycles of Q101. This response lasted close to one year. This patient demonstrated a significant reduction in HPV cell-free DNA that coincided with the initiation of the partial response, and the HPV cell-free DNA was undetectable for most of the time on treatment. Patient B, who remains on treatment at the present time for approximately one and a half years, has had stable disease with tumor burden reduction of approximately 20% observed at week 48, and maintained to the present time at greater than 75 weeks. Notably, this patient has also had complete disappearance of HPV cell-free DNA in the blood since week six. The undetectable HPV cell-free DNA, which is an increasingly recognized biomarker of disease activity, is suggestive of a pathologic complete response, i.e. a potential cure in this patient. who we expect may have surgical resection of the lesion for histopathological analysis. Patient C has experienced tumor reduction after a prolonged period on drug where no resist-based subjective response was initially observed by imaging. In this patient treated with Q101 at 2 milligrams per kilogram, we can see that the first several months appear to demonstrate gradual tumor growth even beyond the 20% threshold used by resist criteria. However, Based upon the overall clinical status, the patient continued treatment. After approximately six months, the tumor began to shrink, and the patient remained on therapy for greater than 18 months after starting treatment with Q101. This observation, consistent with observations made by others, demonstrates that kinetics of T-cell antitumor activity may manifest over a long period of time. The next slide, slide eight, conveys our ongoing survival swimmer plot for the 20 patients dosed the recommended phase two dose of four milligrams per kilogram. The swimmer plot for the 20 patients dosed at the RP2D of four mgs per kg demonstrates a trend of increased survival of approximately 12 months median overall survival compared to the historic reported survival of approximately eight months observed in patients treated in the second line in the Keynote 40 trial of pembrolizumab. As any experienced oncologist understands, the survival with third-line treatment is expected to be less as the disease has further developed and become more unstable. Our evolving data continues to support the premise that treatment with Q101 stimulates the patient's immune system and results in what appears to be a meaningful increase in survival for patients with advanced recurrent metastatic HPV-positive head and neck cancer. This monotherapy data has encouraged our principal investigators and offers a potential path forward to a registrational trial. As showed on slide 9, Q101 and checkpoint inhibition have complementary mechanisms of action, and preclinical studies have demonstrated enhanced response and survival when both are given in combination. In this aggressive HPV-positive murine tumor model, shown in the right panel, the survival curves demonstrated survival of 90% for mice treated with combination of Q101 and anti-PD1, compared to 0% and 20% end-of-study survival for anti-PD1 and Q101 monotherapy, respectively. The demonstration of monotherapy activity in patients bolsters our belief that we should observe complementary mechanistic effects in combination with pembrolizumab. As a reminder, the data from patients treated in the Q101 monotherapy trial clearly supports that Q101 increases the number of tumor-specific T cells in the patient's body. In the combination study with pembrolizumab, it appears that these activated T cells have greater capacity to kill cancer cells when coupled with inhibition of the PD-1 pathway, a major mechanism used by cancer cells to prevent immune-mediated killing. As reported at CITC in November of last year, and as shown on the waterfall plot on slide 10, four of the first 10 available patients treated at the recommended phase two combination dose of Q101 at 4 milligrams per kilogram plus pembrolizumab have experienced partial responses, i.e., at least two consecutive scans demonstrating a cumulative reduction of tumor burden of minus 30 percent or greater. Notably, three of the four partial responses have been observed in tumors with low PD-L1 expression as evidenced by CPS scores of 20 or less. As has been indicated by other studies, tumors that had CPS scores greater than 20 have been more responsive to PD-1 blockade and exhibit higher objective response rates compared to tumors with CPS scores less than 20. The overall response rate of greater than 40% observed with Q101 in combination with pembrolizumab to date compares favorably to the historical objective response rate of 19% observed with pembrolizumab monotherapy in the Keynote 48 study. The follow-up data on these first 10 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 an upcoming oncology meeting. Key observations in patients treated with Q101 monotherapy in the third line and beyond include, as detailed on slide 11, demonstration of single-agent antitumor 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 emerging from survival follow-up in the RP2D cohort. As previously announced, the robust data on Q101's activity in monotherapy and in combination with pembrolizumab enabled the granting of fast-track designation for the treatment of patients in both the first and third line setting. The cumulative data from these ongoing trials with Q101 have provided us with clear evidence of targeted expansion of HBV-E7-specific T cells with antitumor activity as a single agent and as a complementary mechanism with checkpoint inhibition what we believe will broaden patient reach and enhance efficacy of checkpoint blockade therapy as such as such we believe q101 as our first biologic therapeutic from our q100 series represents a potential therapeutic breakthrough for patients and we look forward to providing you with updated additional data at an upcoming oncology conference furthermore We believe the data from Q101 has provided a de-risking and mechanistic validation for additional biologics from the Q100 series, beginning with Q102, as shown on slide 12. Regarding our progress update pertaining to Q102, which targets Wilms Tumor 1 positive tumors in a trial that is enrolling patients with advanced colorectal, gastric, pancreatic, and ovarian cancers, We anticipate completing the dose escalation portion of the trial by mid-year. The treatment has been well tolerated with no DLTs observed to date. We plan to present preliminary data from the dose escalation portion of this trial at an upcoming oncology conference. As a reminder, Q102 and Q101 share 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 one dose escalation study at one milligram per kilogram, a dose at which we observed clear signs of biologic activity with Q101. As slide 13 shows, 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. This trial is actively accruing and will be open at 15 sites throughout the United States. We plan to present additional data at an upcoming oncology conference and look forward to presenting the corresponding data. I will now turn the call over to Ken. Ken?