Cue Biopharma, Inc.

Greetings and welcome to the QBioPharma Investor Update Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad. As a reminder, this conference is being recorded. I would now like to turn the conference over to Dan Passeri, QBioPharma's Chief Executive Officer. Thank you. You may begin.

All right, thank you very much, and good afternoon, everyone. As a reminder, this presentation and discussion is being recorded and will be available on our website for the next 30 days. Also, please be aware that the slides accompanying today's update may be advanced directly by those listening in on the call, and we'll be notifying you as we proceed through the presentation. Joining me on today's call is Dr. Anish Suri. our President and Chief Scientific Officer, Dr. Matteo Levassetti, our Chief Medical Officer, and Carrie Ann Millar, our Chief Financial Officer. As shown on slide number two, 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, August 9th, 2023. On the next slide, which is slide number three, just outlines the agenda for today's call, and I'll begin with a brief summary followed by a niche. A niche will provide you with some background context pertaining to our approach and resulting developments regarding the Immunostat platform with a brief synopsis of associated competitive advantages 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 for 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. Following Matteo, Anish will return with a brief overview of our preclinical pipeline developments. And then that will be followed by Carrie, 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. Now I'm going to turn the call over to Anish. Anish?

Thanks, Dan. As noted in slide four, 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 effective 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 on HSQs have been fine-tuned and optimized to provide protective immunity while preserving the safety of the host. 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-2 selectively to the tumor-specific T cells. This property enables us to create a meaningful therapeutic index to exploit the promise and potential of targeted immune activation in the patient. The same principle can be applied to any other cytokine or immune modulation signals. To the last point, we've 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 platform modularity to address patient needs in many cancers, and I will comment more on this as we discuss our pipeline and potential for expansion into indications with significant market potential. Okay, the next slide, slide five, provides a conceptual framework for maximizing the success of cancer immunotherapies. 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 attributes of our lead clinical candidates that are derived from the IL-2-based Q100 series. As noted here, immunostats are selective engagers of TCRs, of tumor-specific T-cells, and deliver functional IL-2 signals to those very T-cells. The Q100 series architecture is composed of two natural signals. One 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 epitope shown in yellow, that is a tumor-specific peptide sequence. The other natural signal is an affinity-tuned IL-2 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-2 signals is bespoke to nature's selective design and hence results in exquisite specificity. The generation of a therapeutic index for the right tumor-specific T-cell over all other irrelevant T-cells is further supported mechanistically by the elegant live cell microscopy experiments conducted by Dr. Michael Dustin's lab at University of Oxford. Dr. 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. When the same immunostat engages an irrelevant T cell, no such effect is noted. 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 anti-tumor efficacy and tolerability. Importantly, we've had patients in our trials that have continued to receive drug for up to two years, underscoring the durability of the clinical activity and 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. In the frontline setting where anti-PD-1 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 and we have seen an even greater increase in response rate over anti-PD-1 therapy alone. It is well recognized that patients with low CPS scores constitute a significant population and are notably less responsive to 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. We also believe that the clinical data with Q101 have validated and de-risked 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 mcpc. 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 a biologics platform. From a platform modularity perspective, the core IL-2 framework remains conserved between different Q100 series immunostats. 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 three 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. Matteo?