Cue Biopharma, Inc.

Good day and welcome to the QBioPharm second quarter 2024 earnings call. All participants will be in a listen-only mode. Should you need assistance, please signal conference specialists by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. To ask a question, you may press star then one on your touchtone phone. And to withdraw your question, please press star then two. Please note this event is being recorded. I would now like to turn the conference over to our Chief Executive Officer, Mr. Dan Paceri. Please go ahead, sir.

Okay, 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, and we will notify you on what slide we're on throughout the presentation. Joining me on today's call is Dr. Anish Suri, our President and Chief Scientific Officer, and Dr. Matteo Levassetti, our Chief Medical Officer. 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 only as of today, August 19, 2024. I'd like to begin the call by providing you with some context pertaining to our recent announcement focused upon near-term developments with our autoimmune programs and associated corporate restructuring. I'll begin with a brief synopsis of the objectives underlying these measures. And just to underscore, we carefully assessed our strategic positioning, and evaluated various options for optimizing probabilities of success within the challenges and constraints of the current capital market conditions. The measures recently implemented aim to reduce our capital requirements while also achieving enhanced productivity through what we consider to be basically a balanced business model focusing upon accessing capital and additional resources through a series of anticipated strategic partnerships. Furthermore, we've taken measures for our clinical data to further mature to enhance competitive positioning, particularly relating to patient survival data, enabling near-term cost savings and delaying the launch of a capital-intensive trial towards registration. This path provides a higher probability of success as more mature data should bolster the veracity of our mechanistic advantages for establishing the potential of a new standard of care for cancer patients. As shown in slide number three, we believe we've developed a breakthrough proprietary therapeutic approach to establish a new standard of care for treating both cancer and autoimmune diseases by restoring immune balance to the patient's immune system. As Matteo will elaborate upon shortly, our data from the ongoing Q101 Phase 1B trial clearly demonstrates evidence of substantial prolongation of survival in patients treated with Q101, monotherapy in the second line plus setting, and emerging data from the combination trial in front line with Keytruda, that's pembrolizumab, that also appears to be following a similar pattern as what we saw with the monotherapy trial. We believe this data to be quite remarkable, underscoring what we believe to be the true competitive positioning of our approach. As such, it's our intention with the measures taken to enable clinical data to further develop and mature in support of our foundational platform that we believe can induce effective and long-lasting anti-tumor activity or can be harnessed to rebalance the aberrant immune responses to address autoimmune diseases. We've also made significant progress with our lead autoimmune disease program, Q401, being developed in collaboration with our partner, Ono Pharmaceutical, to address multiple autoimmune and inflammatory diseases, such as rheumatoid arthritis, graft-versus-host disease, lupus, inflammatory bowel disease, psoriasis, multiple sclerosis, amongst others, representing large, multibillion-dollar market potential addressing significant unmet medical need. Through this partnership, we've made impressive progress to date in moving towards selection of a lead candidate, which we anticipate in the first quarter of the coming year. Our collaboration with Ono has been highly productive and supportive. resulting in a growing body of promising data demonstrating the ability of Q401 to generate and expand regulatory T-cells, or Tregs, fostering disease control in several disease models tested to date. As a reminder, QBioPharma has retained an option to a 50% U.S. co-development, co-marketing right to Q401. Turning to 501, this program continues to advance and progress forward with the potential of eliminating autoreactive B cells with a highly selective and well-tolerated biologic. This program has the promise of addressing multiple B cell-mediated autoimmune diseases, such as lupus, myasthenia gravis, Sjogren's disease, and myositis. amongst others representing significant unmet medical needs with large multi-billion dollar market potential. Furthermore, the same mechanism of action that we would be seeing in B-cell ablation for autoimmune disease may be deployed to address B-cell malignancies such as B-cell lymphoma. We're presently assessing strategic partnering alternatives for furthering the development of this promising program and look forward to providing updates as they become available. We have positioned ourselves with a growing portfolio of highly promising drug candidates in both oncology and autoimmune disease, all of which represent significant market opportunities addressing major unmet medical needs. We believe we've de-risked and validated our therapeutics platform with the existing data sets from our Q101 and Q102 programs and have established foundational preclinical data pertaining to our autoimmune programs with potential to rebalance the patient's immune system to restore health. We've implemented a cash-efficient business model, enabling a reduction of capital requirements with an emphasis on validating near-term partnering structures. I'm going to now turn the call over to Anish, who will describe the core attributes and advantages of our approach to treating autoimmune disease, as well as provide some additional context on our underlying platform developments for both oncology and autoimmune disease. After Anish, Matteo will provide further updates on the Q101 and 102 clinical trials and highlight the importance of the maturing data sets with particular attention to the survival metrics that are emerging. I'll then return for a brief summary before opening the call up to questions. Anish?

Thanks, Dan, and good afternoon to all listening in on today's call. I'll start by briefly summarizing our platform and the significant potential of our approach for restoring immune balance. for treating cancers and autoimmune diseases. As described previously, the Immunostat platform enables selective modulation of disease-relevant immune cells while avoiding broad perturbations of the immune system. This approach allows us to maximize efficacy while preserving patient safety. As Dan indicated previously and as summarized on slide three, we have now clinically validated immunostats via the Q100 series, that selectively and safely delivers the potent cytokine IL-2 along with a TCR activating signal to preferentially activate tumor-specific T-cells while sparing all other irrelevant T-cells. This selective stimulation allows for the generation of a therapeutic index for IL-2, which has eluded many others trying to develop IL-2-based cancer therapies. In over 120 patients dosed, we have demonstrated a remarkable increase in efficacy with favorable tolerability. Matteo will provide further details on the latest clinical data that continue to demonstrate impressive benefit for patients being treated with Q101 and Q102. On the autoimmune front, we have focused on two distinct and highly promising approaches to reset immune balance. Q401 is a novel bispecific that stimulates the generation and expansion of regulatory T cells. Regulatory T cells, or Tregs, possess the ability to dampen and control autoreactive lymphocytes, hence are an important cell type to maintain immune homeostasis and health. Q401 has been partnered with Ono Pharmaceuticals, and this collaboration continues to move forward strongly. In addition to Q401, we've also made significant progress developing Q501 from the Q500 series to enable T cell-mediated depletion of B cells. This approach has the potential to deliver CAR T-like efficacy in a biologic while preserving patient safety, which offers significant differentiation from other competing approaches. Both Q401 and Q500 series are designed to address large patient populations across numerous autoimmune and inflammatory diseases with a multi-billion dollar market potential. We will expand on both programs in the next few slides. The next slide, slide four, exemplifies the unique attributes of Q401 in induction and expansion of Tregs. Q401 is a bispecific composed of the two key cytokines IL-2 and TGF-beta that are known to convert peripheral CD4 T cells into Tregs, as well as expand pre-existing natural Tregs. This ability to induce new populations of Tregs provides Q401 with the prospects of significant superiority over other approaches deploying IL-2 variants to focus on only the pre-existing natural Tregs. As shown in slide four, we believe the mechanism of action of Q401 to enhance Tregs is qualitatively and quantitatively superior to IL-2 mutines targeting CD25, which is the high affinity subunit of the IL-2 receptor expressed on regulatory T cells. Slide five highlights datasets that show superiority of Q401 over an IL-2 mutine analog currently in clinical development for Treg generation. As shown on the left side of the slide, in an in vitro human MLR assay, which is an in vitro model for graft versus host disease, Q401 induces differentiation and expansion of Tregs. In contrast, a Treg-directed IL-2 mutine is unable to achieve these effects. The bottom left panel confirms that both IL-2 and TGF-beta signals are needed for Treg generation. Either alone is unable to achieve this effect. As shown on the right side and as previously discussed, short-term administration of Q401 results and long-term protection from autoimmunity, in this case, autoimmune gastritis. In our ongoing collaboration with Ono Pharmaceuticals, we have further extended the in vivo efficacy with Q401 in several other disease models where we have noted a significant increase in Tregs accompanied by a notable decrease in pro-inflammatory cytokines. Let's now move to slide six to provide an overview and update on the Q500 series for B cell depletion. The primary goal behind the design of the Q500 T cell engagers was to achieve T cell mediated depletion of B cells while avoiding the adverse effects of systemic immune activation and broad engagement of all T cells. Our approach enables the potential to achieve CAR T-like efficacy while avoiding the safety pitfalls of pan T cell engagers. By design, the Q500 series immunostats bind to CD19 on B cells and effectively paint the B cells with a viral epitope, such as CMV. These B cells are then readily recognized and killed by the memory antiviral T cells, as shown in the slide. Engaging virus-specific T cells, or VSTs, offers several advantages. These are trained killer T cells present in high frequency across the human population. They are localized in diseased tissue and perform rapid killing of targets. And due to their specificity of virus antigens, the VSTs avoid the risk of potential reactivity against cell tissue or systemic immune activation, as would be with pan T cell engagers. Importantly, and as shown in slide seven, VSTs, in this case, CMV-specific memory T cells, can achieve the same degree of killing of B cells as pan T cell engagers. in this case an anti-CD19, anti-CD3 bispecific molecule. Note here that the killing is specific to the engagement of CMV T-cells since a Q500 molecule expressing an HIV epitope is unable to mediate B-cell killing since HIV-specific T-cells are largely absent in most individuals. Slide 8 further exemplifies the difference in safety and cytokine production between Q501 and pan T-cell engagers. Due to their high selective engagement, the Q501 molecule does not result in copious production of inflammatory cytokines, such as interferon gamma and TNF, as shown here. In contrast, a pan-T cell engager molecule, due to its anti-CD3 binding to all T cells, results in significantly high levels of cytokine release, which ultimately compromises patient safety and drug tolerability. The following slide, slide 9, highlights some of the notable points of differentiation between Q500 CAR-T approaches and pan T cell engager molecules. Note that all three approaches involve T cell mediated killing of target B cells, but it's only the Q500 series that can selectively engage trained memory killer T cells and redirect them to kill B cells. The selective engagement while avoiding systemic activation results in a significant reduction in cytokine release, and related toxicities, which should favor patient safety while preserving efficacy. We believe the Q500 series of biologics are likely positioned as the best-in-class T-cell engagers for B-cell depletion and could address a very large segment of autoimmune patients across many indications. In summary, there are three key takeaway messages. First, due to the shared core structural framework, the clinical de-risking and validation of immunostats in oncology via Q101 and Q102 including lack of clinically relevant immunogenicity, bolsters and supports the clinical application of Q500 series for B-cell depletion in autoimmunity. Second, selective harnessing of antiviral memory T-cells to kill B-cells circumvents the safety risk associated with systemic T-cell activation, as noted with pan-T-cell engages. And third, data demonstrating comparable killing while avoiding high levels of pro-inflammatory cytokine production positions the Q500 series to achieve desirable efficacy while not compromising patient safety, which is of highest clinical relevance when considering therapeutic applications in autoimmune diseases. With that background and update, I'll turn the call over to Matteo to describe the maturing clinical data from the ongoing oncology trials. Matteo?