Good afternoon, ladies and gentlemen, and welcome to the Cue Biopharma Third Quarter 2023 Earnings Call. At this time, all lines are in listen-only mode. Following the presentation, we will conduct a question-and-answer session. [Operator Instructions] As a reminder, this call is being recorded today, Thursday, November 9, 2023. I would now like to turn over the conference to Dan Passeri, Chief Executive Officer. Please go ahead.

Yeah. 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 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 of what slide we're on throughout the presentation. Joining me on today's call is Dr. Anish Suri, our President and Chief Scientific Officer; Dr. Matteo Levisetti, our Chief Medical Officer; and Kerri-Ann Millar, our Chief Financial Officer. As shown on Slide number 2, the 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, November 9, 2023. The next Slide, Slide number 3, outlines the agenda for today's call, and I'll begin with a brief summary overview of our therapeutic platform and core competitive positioning, which is bolstered and further validated by the recent data update presented this past weekend at SITC. I'll then turn the call over to Matteo, who will provide a detailed synopsis of our clinical data from both the monotherapy and combination portions of the ongoing CUE-101 trial, as well as the highly encouraging early signs of clinical activity from the dose escalation portion of the CUE-102 monotherapy trial. As a reminder, these data are representative of our modular Immuno-STAT platform, which we believe has significant potential for broad market applications in cancer immunotherapy, autoimmune and inflammatory diseases, as well as chronic infectious diseases. After Matteo, Anish will provide a further details of our platform developments, underscoring the far-reaching potential of our approach for selective modulation of disease-specific T-cells and the potential for superior differentiation. Following Anish, Kerri will provide an overview of our financials for Q3 and guidance…

Thanks, Dan. Good afternoon to everyone listening in on today's call. I am particularly pleased to provide you with this summary update as the clinical data from the ongoing CUE-101 trial continues to demonstrate highly encouraging and robust metrics of clinical benefit for heavily pretreated recurrent metastatic HPV+ head and neck cancer patients treated with monotherapy and for newly diagnosed patients with recurrent HPV+ head and neck squamous cell carcinoma treated in combination with pembrolizumab. As shown on Slide 5, data from the ongoing clinical trials with CUE-101 as monotherapy and in combination with pembrolizumab have provided clinical proof-of-concept and de-risking of our Immuno-STAT platform. The latest data generated to date in 2023 continues to support prior observations and further enhances our confidence in CUE-101 as a potential therapeutic for patients battling HPV+ head and neck cancer. As previously and consistently stated, we believe CUE-101'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. Recurrent metastatic HPV+ 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 CUE-101 is in fact stimulating the targeted cancer-specific T cells within these patients, resulting in demonstrable anti-tumor effect. Furthermore and importantly, we continue to observe an evolving pattern of disease control and enhanced survival in the monotherapy trial. We believe this enhanced survival is due to the superior qualitative features of tumor-specific T cells given CUE-101's mechanism of action, especially in the tumor microenvironment and the recent description of the role of IL-2 in generating potent effectors CD8+ T cells. On this note, enrollment in the neoadjuvant trial is progressing well and preliminary observations demonstrate expansion of T cell…

Thanks, Matteo, and thank you all for joining this call today. As Matteo highlighted, the maturing clinical data with CUE-101 and 102 bolstered the validation for Immuno-STATs as a differentiated class of T cell engager therapeutics that can be deployed widely for immunotherapy of cancers. To that end, Slide 17 depicts the opportunity for expansion of the CUE-100 series to generate therapeutic molecules targeting numerous cancers. Note that the core IL-2 components remain the same among all therapeutic candidates, with the primary difference being the tumor antigen HLA complex that provides selectivity for the cancers being targeted. Following the success with our clinical assets, CUE-101 and CUE-102, we have designed and manufactured a rich pipeline of preclinical Immuno-STAT candidates that can be readily progressed towards the clinic. Examples of some of these preclinical candidates include Immuno-STATs targeting mutated KRAS isoforms, especially the hotspot mutational variants at the G12 possession, including G12V and G12D, and additional Immuno-STATs targeting well-characterized tumor antigens such as MAGE A4, PRAME, and COL6A3, which is derived from a tumor-specific splicing variant of collagen type VI alpha-3 protein and appears to be shared across many solid cancers. Many of these preclinical Immuno-STATs have also been validated in functional T cell assays. It is important to highlight that the evolving Immuno-STAT pipeline encompasses multiple cancer targets and multiple HLA alleles, which together provide broad patient coverage for many cancers. In addition, we've also evolved the platform to accommodate multiple tumor antigens and personalized neoantigens. This extension of our platform is known as Neo-STAT, as shown on the right side of this slide. In the Neo-STAT framework, the peptide binding pocket of the HLA is empty, which allows us to readily conjugate different tumor epitopes to generate off-the-shelf, therapeutic molecules. Neo-STATs are a potential solution for tumor heterogeneity and…

Thank you, Anish. Turning to Slide 21, I'd like to provide a brief update on our financial results for the three months ended September 30, 2023. During the third quarter, the company reported collaboration revenue of approximately $2.1 million, as compared to $68,000 for the same period in 2022. Revenue in the third quarter was primarily due to work related to our collaboration with ONO Pharmaceuticals for CUE-401, which Anish just described. Research and development expenses were $9.9 million and $7.6 million for the three months ended September 30, 2023 and 2022, respectively. The increase is due to higher clinical expenses, stock-based compensation, and research and laboratory expenses in the third quarter. General and administrative expenses remained steady at $3.6 million and $3.5 million for the three months ended September 30, 2023 and 2022, respectively. As of September 30, 2023, the company had approximately $54.7 million in cash and cash equivalents, $40.3 million in working capital, and $45.1 million common shares outstanding. We expect our current cash and cash equivalents to fund operations through 2024. I'll now turn the call back over to Dan for closing remarks. Dan?

Yeah. Thanks, Kerri. As conveyed at SITC last weekend and now summarized on this call, the design of our Immuno-STAT molecules achieves selective modulation of disease-relevant T cells, while sparing the detrimental effects of the stimulation of the vast majority of irrelevant T cells. In essence, we believe we have achieved the biologic equivalence of precision targeting, thereby creating a therapeutic window for potent cytokines such as IL-2. This desired profile enables combinations with, for instance, checkpoint inhibitors, wherein the complementary mechanism of actions should provide enhanced efficacy while not compromising tolerability and patient safety, as shown on Slide 22 with our clinical data from CUE-101 plus pembrolizumab in frontline HPV-positive refractory and metastatic head and neck cancer patients. Turning now to Slide 23, let's review the modest overall response rates reported on checkpoint inhibitor monotherapy in various solid tumor cancer types. It's important to note that while checkpoint inhibitors opened up the potential promise of immuno-oncology, their impact on antitumor efficacy is primarily dependent upon the presence of a robust anti-tumor T cell repertoire. As such, the rational combination of checkpoint inhibitors and Immuno-STATs increases the probability for patients to derive enhanced therapeutic benefit from immunotherapy. And that's actually shown if you look at the head and neck cancer patient. We increased the overall response rate from 19% with pembrolizumab alone in frontline to 47% in the combination. Okay, finally, let's move to Slide 24. This shows the anticipated milestones and accomplishments we anticipated achieving over the next year, including the defined prospective registration path for CUE-101, as well as multiple clinical milestones with our two clinical candidates and several solid tumor types. It's important to note that we're very well positioned for strategic alignment with prospective partners, recognizing the potentially disruptive implications of our emerging data. We look forward to continuing our progress forward into a highly productive and transformative 2024. With that, I'm going to turn the call back over to the operator, and we'll now open the call, open the questions. Operator?

Thank you. Ladies and gentlemen, we will now conduct a question-and-answer session. [Operator Instructions] Your first question comes from Stephen Willey from Stifel. Your line is now open.

Hi, guys. This is Torian (ph) for Steve. Can you guys hear me, okay?

Yes. Thank you.

Thank you. Thank you for taking my questions and congrats on the data update. I have just two quick ones on my end. So the first one is starting with CUE-101. I understand that you guys submitted a request to FDA, and it looks like you guys are now planning on defining a registration path in the beginning of 2024. And I'm wondering what the format of that communication be. Would it be just a press release or do you think you will likely disclose that information during earnings call, et cetera.? And second is related to CUE-102, and very interesting data. And I guess my question would be, what gives you guys the confidence in pursuing colorectal and pancreatic cancers in expansion cohorts besides, high prevalence of WT1 expression in these tumor types? That would be it. Thank you very much.

Okay. First question, I want to emphasize that these -- and the request for discussions with the FDA are basically our initial discussions regarding registrational trial design. And the first foray is in the second line and beyond monotherapy. But we view this as a really important sort of foundational discussion to build support for our subsequent dialogue with the FDA for defining future registrational paths, et cetera. I also want to emphasize we're in the -- we are engaged in some partnerships and partnering discussions, and we want to be cognizant of the fact that defining registrational trials need to correspond with those partnering objectives as well. So this is an important initial interaction with the FDA to establish kind of foundational support for the mechanism of 101 as a monotherapy, which then builds on our subsequent discussions. So that's really the strategy there. With 102, again, we have done a basket study in the dose escalation. Initially, we were looking at focusing on colorectal, but based on the observations we're seeing, we're looking at several tumor types that we would likely do a patient expansion in. And I'm going to turn this over to Matteo, if he wants to elaborate on that.

Yeah. Thanks, Dan. Just to add at a couple points. We're very happy with the tolerability profile that we've observed to-date. In addition to the signs of antitumor activity in multiple indications. And so just to sort of set the context for this late line of colorectal cancer, these patients are very advanced, very refractory. And if you actually look back to the approval of stivarga, regorafenib, in colorectal patients, there was about a 30% disease control rate at six weeks that ultimately was then associated with a 1.4 month increase in survival. And that led to the approval of that drug in late line colorectal cancers. So observing stable disease in a high proportion of patients, even at six weeks is significant. And then furthermore, we have patients now across several indications with stable disease beyond 18 weeks, and that includes patients with pancreatic cancer. And then as we've shown, the patient with gastric cancer that has a very close to threshold partial response at 24 weeks continues on therapy. So we're very encouraged, as are our investigators, by our observations. And in fact, our investigators are really keenly interested in pursuing all the indications. And we, going forward, will consider how doing so and the timing of that fits in our overall development strategy for CUE-102.

Very helpful. Thank you.

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

Hey, guys. Thanks for taking the questions and congratulations on all the data that was released. It's nice to see the continued improvement in overall survival. Several questions from us. Maybe just starting off with the CUE-101 series. When we talked about that patient who got a PR, quite late in the whole process, can you talk a little bit about how many doses that patient actually received? Do they continue to receive doses or has the dosing schedule been modified at all? And then sticking with CUE-101, the combination study, if we focus just on the low CPS patients, can you talk a little bit about the duration of response and maybe the PFS as well for those patients?

Yes, Matteo, you want to take that?

Sure. So thank you for the question. Regarding the patient that had stable disease for 24 months, this is, again, the patient that at six weeks had undetectable cell-free DNA. So you asked regarding the length of their treatment. It was a complete 24 months. This patient did have their regimen reduced from Q3 to Q6 weeks. After approximately 12 months or 14 months of treatment, but they completed the whole two years of therapy. I'm sorry. Now, the second question was in terms of how…¦

Durability, low CPS patients, and the duration, progression-free survival, like -- is that durable?

Yeah. So the durability, really is, it's evolving. So it's maturing. So we have several patients with ongoing objective responses. So it's really a bit premature, I think, to define the duration of response. It's approximately 30 weeks now, but really maturing with several patients remaining on treatment. The median PFS is close to six months. And again, that compares favorably to the monotherapy data where it was approximately three months from KEYNOTE-048. But again, as the duration of response needs time to further mature, the PFS will be maturing as well in parallel.

Got it. And then just you had mentioned -- you had made some comments, Matteo, in the call regarding the neoadjuvant trial. I was wondering if you could provide a little bit additional color on those observations, maybe -- I mean, anything you can provide. Is it just CD8 and CD4 cells that are moving up or are there NK cells involved as well? And kind of what are next steps and when might we see that data?

Certainly. So this is really an exciting trial and a wonderful opportunity to look at the effects of CUE-101 on the tumor microenvironment in a setting where one can obtain substantial amounts of tissue from biopsy. And so, again, just to point out that this is an investigator-sponsored trial at Washington University. However, we have been able to see some preliminary data, which is really very, very encouraging. And what we've seen is expansion of T cell clonality in the tumor microenvironment. And increases in natural killer cells in the tumor microenvironment after two doses of CUE-101. So this study continues to enroll. I think we anticipate enrollment may be complete by the end of next year. And we are respectful of the investigator's desire to publish this work when the time is right. But it really, certainly, is very supportive of everything we've observed to-date in our clinical study.

Got it. I'll ask one more and then just hop back in the queue. As we think about WT1, and that program and the advancement of that program, I kind of look at CUE-101 as kind of the poster child. And so it begs the question, what potential combinations might you ultimately want to be exploring, as you move that program forward?

Yeah. So great question. Thank you. I think, clearly, as we learn more about the activity of CUE-102 and the different tumor types that the rational next step with regards to development would be to look at combinations. And potential combinations, I think, will likely depend on which tumor Type 1 is talking about. And so, we looked, for example, at gastric cancer, where we've seen this tumor reduction of 24 weeks duration. Considering a combination with anti-PD1 or checkpoint inhibitor, given the history of some, although limited activity in some subsets of gastric cancer, I think in other indications, like colorectal cancer, it would be very interesting to move up one or two lines of therapy and think of combinations, perhaps, even with chemotherapy or anti-VEGF therapy, for example. But this is certainly an area of very active deliberation for us. And it, of course, dovetails, importantly, with our strategic ongoing activities with potential partners.

That’s great.. Thanks for taking the questions. I’ll hop back in the queue.

Thanks, Reni.

Your next question comes from Ted Tenthoff from Piper Sandler. Your line is now open.

Great. Thank you very much. And, again, I appreciated all of the SITC and the update. Just kind of looking at now that you've really got Immuno-STAT proof-of-concept, what other are some of the antigens? I know that you've talked about KRAS in the past. Would potential partners be interested in looking at their own antigens on this active construct or are they more looking at kind of the existing products or maybe even kind of a mixture of both?

Yeah. I'll turn that over to Anish. Thanks, Ted.

Yeah. Hi, Ted and thanks for the questions. So, Ted, as you well saw with some of what we've said in the expansion, going after primary cancer drivers is obviously a low-hanging fruit. So, mutated KRAS, you're aware of the G12C small molecule covalent inhibitor from Mirati being approved and the Amgen compounds. We believe the valine and the aspartic acid, well appreciated, are much larger patient populations, particularly in the three major cancers of colorectal, lung, and pancreatic. And they do donate T cell epitopes. So, just in that space, for example, Ted, we've got four different KRAS molecules addressing G12B and G12D on a couple of different HLA alleles. We've also got strategies looking at other primary mutated cancer drivers. And that is still early in the pipeline, but we have confidence they'll be validated. We've got primary tumor drivers like MAGE-A4 and Cancer-Testes Antigens that offer very attractive opportunities and perhaps some level of validation through the ongoing work of others looking at TCR T cell therapy approaches. Of course, ours is with the biologic, so a very different application and perhaps a bit more easy to sort of think about from the commercial and patient accessibility viewpoint. We've got interest on these sets of antigens from certain sort of parties to what you referred to going after some of these primary drivers. But then, as you well know, there is a significant community out there that has been focused on discovering and doing their own work on bespoke antigens, which the platform can easily be deployed to drug those moieties. To that end, Neo-STAT becomes a fantastic opportunity, and that's one of the reasons we sort of highlighted that modality, even though that is an extension of the Immuno-STAT. The opportunity there is the fact that you can go after multiple antigens, Ted, and it's the same core IL-2 framework. So, we do believe the efficiencies and the advantages that we've demonstrated, the CUE-101 and CUE-102, should apply to Neo-STAT as well. So, there's, again, we look at this in three sort of broad buckets. We look at driver antigens, where single dominant antigens should have benefit. And CUE-101 is a great example because E7 is a viral proto-oncogene in the case of HPV-driven cancers. And by the way, that data is in head and neck cancer. That same molecule can go to other indications like cervical, penile, anal, vulva cancers as well. CUE-102, with what Matteo just described, follows up a beautiful example of a onco-fetal antigen that is selectively expressed and has activity. And then KRAS, for obvious reasons, including the MAGE A4, PRAME follows suit. And then we've got this opportunity to go after multiple different antigens, where one can simply deploy the platform. And that's the reason I highlighted the plug-and-play approach virtually has a potential to generate therapeutics.

Thanks. Super helpful. Really exciting time for the company. Thanks, guys.

Thank you, Ted.

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

Hey, guys. Thanks for taking the follow-up. Yeah. You mentioned on the call partners and partnerships. And I guess, I'd like to just, if you can, provide a little bit additional color as to maybe how those discussions are going. Should we be thinking about, I don't know, sort of the who's who of checkpoint inhibitors are who you're kind of talking to or are there other types of potential partners for one-on-one that you're talking with? And I guess just as a follow-up to that does a partnership -- is that necessary to move into a pivotal study or is that something that you believe after the FDA discussion is complete you might need to and want to take on your own? Thanks very much.

You're welcome. So, important question, Ren, and it's a complex question, right? It doesn't have a simple answer. So, let's start-off with the last part of the question. It's not necessary for going forward with a pivotal study, but I would say with the current market dynamics that the biotech sector, particularly oncology, is confronting with the headwinds in the capital markets, we have limited resources. And we're trying to look at dynamically how do we continue to evolve the platform for maximizing patient reach and demonstrating the value of our platform for addressing serious disease, cancer, autoimmune, et cetera. So, we're looking at partnering strategies that give us flexibility but still engaged in involvement in the drugs development. We don't want to become a licensing company. We want to become a strategic collaboration partner. And I would say Ono was a great example. We have a co-development option with them in that collaboration. In terms of the characterization of the companies we're talking to, it's the full spectrum. We're certainly talking to the who's who. I'd say what's intriguing is, first of all, we very deliberately did not go out with a BD emphasis early on in our development. We wanted to build a sound, substantive data package based on rigor and solid data that we could stand on. We're also getting sort of inbound inquiries, and that's actually very encouraging. So, we're talking to a spectrum of potential partners, and I would say a sort of spectrum of opportunities and different sort of structures that we're assessing. So, I appreciate the question. I can't answer it with any more detail for obvious reasons, but I'm doing the best I can to address your question.

Yeah, enough. Thanks. I appreciate that. Good luck going forward.

Thank you.

[Operator Instructions] There are no further questions at this time. Daniel Passeri, please proceed with your closing remarks.

Yeah, great. Thank you. First, we want to thank those of you listening in to this call and recognizing the importance of our mission towards developing these important novel therapeutics for enhancing patient treatment outcomes for debilitating disease. We want to thank our employees for their consummate dedication and professionalism helping us achieve our mission. And obviously, we want to thank our shareholders and Board of Directors for their support. Most importantly, we want to thank the patients and their families participating in these ongoing and important trials. So, thank you again for listening in and take care. Thank you.

Ladies and gentlemen, this concludes today's conference call. Thank you for joining. You may now disconnect.