Cue Biopharma, Inc.

Greetings and welcome to the Cube Biopharma update call. At this time, all participants are in listen-only mode. The question and answer session will follow the presentation. If anyone should require operator assistance during the conference, please press start and 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, Cube Biopharma's Chief Executive Officer. Thank you, Sal. Please begin.

Thank you, and good afternoon, everyone. Before I begin, I'd like to remind everyone that you have the slides in front of you that you need to operate manually, and we will notify you what slide we are on. Joining me on today's call is Dr. Anish Suri, our President and CSO, Dr. Ken Pienta, our Acting Chief Medical Officer and Dr. Matteo Levassetti, our Senior Vice President of Clinical Development, as well as Kerry Millar, our Chief Financial Officer. This conference is being recorded and will be available on our website for the next 30 days. As a reminder, and as shown here on slide number two, this presentation An overview may contain some forward-looking statements, and any forward-looking statements made during this call represents the company's views only as of today, November 14, 2022. Our agenda for today's call is shown on the next slide, slide three. I'll begin by providing an overview of our competitive and strategic positioning based upon data from both our monotherapy trial of Q101, as well as the data just recently reported at CITSE from our Q101 and Keytruda combination trial. Matteo and Ken will provide a review of this data in further detail momentarily, but first I want to provide context pertaining to the underlying implications and importance of the datasets observed to date. As you are aware, the ultimate promise of immunotherapy is to enable the intrinsic potential of a patient's immune system to recognize and kill cancer. We believe through our representative data generated from both our monotherapy trial and combination trials of Q101, our IL-2-based Q100 series is now well-positioned to become a first-in-class selective T-cell engager and best-in-class IL-2 for cancer immunotherapy, as shown here on slide number four. The data bolsters our belief that the demonstrated mechanism of action and resulting activation and amplification of cancer-specific T cells will mechanistically complement and enhance therapeutic benefit derived from checkpoint inhibition, such as PD-L1 inhibitor Keytruda. We believe the compilation of data from both the monotherapy and combination trials supports Our central thesis of selective activation of cancer-specific T cells while avoiding systemic immune activation will enhance the desired anti-tumor efficacy. The recent data presented at CITSE positions us well to push forward and potentially transform cancer therapy where patients' own immune systems can be harnessed to the fullest extent to eradicate cancer. I'm now going to turn the call over to Anish, who will provide a brief synopsis and overview of the key mechanistic features of our selective T-cell engager, the IL-2 base Q100 series, and he'll then turn the call over to Ken and Matteo to review the supporting efficacy data that has emerged from the monotherapy trial and provide an update from our recent CITSE presentation pertaining to to the current efficacy data from our combination of Q101 with Keytruda and frontline HPV-positive head and neck squamous cell carcinoma patients. Manish?

Thanks, Dan, and welcome to all listening to this update. As noted in the next slide, we all appreciate the fact that selective activation of tumor-specific T cells is central to successful outcomes from cancer immunotherapy. However, there are biological constants that nature has imposed that must be considered when thinking about tumor-specific T cells. One, the frequency of tumor-specific T cells in a patient is extremely low. Greater than 99.9% of T cells in a patient have no relevance to cancers. So how does one go about selectively activating tumor-specific T cells while sparing the broad activation of all other T cells? Another biological constant is the fact that the only unique marker on an anti-tumor T cell is the tumor-specific T cell receptor, or TCR. There are no cell surface markers that exhibit an absolute fidelity to the anti-tumor T cell repertoire as the tumor-specific TCR. For example, PD-1 expression is a shared phenotypic marker, or CD8 expression is a shared lineage marker, but neither are unique to an anti-tumor T cell. Hence, to exploit this unique selectivity, we've developed the Immunostat platform to harness the TCR specificity to activate tumor-specific T cells. We believe, as supported by our clinical data, that this approach is differentiated in terms of both safety and efficacy outcomes over other modalities that attempt to activate the immune system in a non-selective manner. The next slide, slide six, depicts the core structure of an Immunostat molecule derived from our IL-2-based Q100 series, which is the major focus of today's presentation. As shown here, the Q100 series immunostats harness the TCR selectivity via the stabilized peptide HLA molecule to target an affinity-attenuated IL-2 variant selectively to tumor-specific T cells. The co-signaling via the TCR and IL-2 receptors on the right anti-tumor T cell results in T cell activation and expansion. In contrast, if this molecule encounters the vast majority of irrelevant T cells in the patient, that is greater than 99.9% of irrelevant T non-tumor-specific T cells, the attenuated IL-2 on its own is very weak. Hence, with this unique bias, we have created a therapeutic index for IL-2 via selective focusing on tumor-specific T cells over all other cells. This strategy also forms the mechanistic basis for targeting numerous other activation signals, including other cytokines such as IL-12, IL-15, IL-21, et cetera. Two additional aspects. of the Q100 series are important to appreciate. One, the primary core IL-2 framework is largely conserved between different therapeutic candidates. The primary difference from one therapeutic candidate to the next is the 9 to 10 amino acid T cell epitope depicted by the yellow circle in the diagram in the slide. Due to this conserved structure, we believe the clinical proof of concept with our first clinical candidate, Q101, has dearest the entire platform. This conclusion is supported by the IND approval by the FDA earlier this year for our second clinical candidate, Q102, wherein based on the clinical safety data from Q101, we did not need to perform any additional IND-enabling toxicology studies and were allowed to start the Q102 trial at a MIG per gig dose, which is a clinically active dose from our experience with Q101. Both Q101 and Q102 are 99% sequence identical, except for the 9 to 10 amino acid T-cell epitope. Q101 targets a T-cell epitope from human papillomavirus for HPV-driven cancer, such as head and neck cancer, while Q102 targets a T-cell epitope from Wilms tumor 1, or WT1, an oncofetal antigen widely expressed by many solid and hematological cancers. The other key aspect of the Q100 series immunostats pertains to their favorable stability and manufacturability metrics as a biologic platform. These are antibody FC fusion proteins that follow established manufacturability and CMC protocols for many decades of commercial monoclonal antibody production. The shelf stability for the Q101 GMP drug product, our first clinical candidate, is greater than 36 months, which underscores the robustness of rational protein engineering. Let's move to the next slide, slide seven. Based on the generation of a therapeutic index for IL-2 by selective targeting of tumor-specific T cells, we believe that the Q100 series has the potential to be the best-in-class IL-2 modality for cancer immunotherapy. As shown here, the improved safety and tolerability coupled with the anti-tumor T cell selectivity possessions the Q100 series in a significantly different bracket when compared to all other IL-2 variants that are being pursued none of which are selective for the tumor-specific T cells. In fact, most of the focus of other IL-2 variants has been on modulating IL-2 receptor interactions, but little thought towards anti-tumor T cell selectivity. This lack of biological relevance will continue to generate suboptimal clinical outcomes, as recently evidenced with the clinical data sets from the recent trials from the pegylated IL-2 and the non-alpha IL-2 modalities. Finally, let's move to slide eight that highlights supportive data for biological selectivity and activity of the IL-2-based Q100 series. The panel on the left shows selective engagement of the Q100 series immunostat with an antigen-specific T cell. These data were generated by the lab of Dr. Michael Dustin at University of Oxford. Dr. Dustin has been a pioneer in describing the T cell immune synapse that leads to downstream activation and effective function. As shown here, the Q100 series immunostat only forms an immunological synapse shown in green with the antigen-specific T cells wherein both the TCR and IL-2 signals are operational. The same molecule with an irrelevant T cell as shown in the bottom left panel demonstrates no immune synapse in absence of TCR engagement. The middle panel shows selective expansion of tumor-specific T cells from primary human blood samples while no off-target effects are noted with irrelevant T cell specificities. This is exactly in line with the molecular design of the drug, that is selective expansion of tumor-specific T cells while sparing all other non-specific T cells. The panel on the right shows intratumoral infiltration and expansion of tumor-specific T cells in an HPV-driven cancer model in mice. Note that in this study, not many T cells are evident in the vehicle treated mice or in mice treated with the anti-PD-1 antibody alone. In contrast, a significant number of T cells are present after monotherapy with Q100 series immunostats, and this population is further enhanced in combination with anti-PD-1 antibody treatment. We believe this ability of the Q100 series molecules to turn a cold tumor hot by selectively activating the right T cells is a key differentiating feature of our drug design. Similar observations are also evident from the early emerging data from the ongoing mechanistic clinical trial with Q101 in a neoadjuvant setting in locally advanced head and neck cancer patients. With that background on our differentiated mechanism for IL-2 targeting, I'd like to now pass the call to Ken Pienta and Matteo Levesetti to share the exciting clinical data from the ongoing trials with head and neck cancer patients with our lead clinical candidate, Q101. Ken?