Greetings and welcome to the Cue Biopharma Update Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the presentation. [Operator Instructions] As a reminder, this conference is being recorded. I would now like to turn this conference over to Mr. Dan Passeri, Cue Biopharma's Chief Executive Officer. Thank you, sir. You may begin.

Thank you, and good afternoon everyone. Just to remind you, as we proceed through the presentation we'll convey which slide we're on and you can advance the slides directly. We appreciate your time and interest in our update call regarding our ongoing trials of CUE-101, as well as CUE-102. Our initial representative drug candidates of the IL-2-based CUE-100 series. Joining me on today's call is Dr. Anish Suri, our President and Chief Scientific Officer; Dr. Ken Pienta, our Acting Chief Medical Officer; and Dr. Matteo Levisetti, our Senior Vice President of Clinical Development; and Kerri 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 #2 of this presentation. An overview may contain some forward-looking statements, and any forward-looking statements made during the call represents the company’s views only as of today, August 23, 2022. So Our agenda for today's call is shown on the next slide. As an introduction and each will provide a synopsis of our progress to date, as well as describing our strategic and competitive positioning prior to turning the call over to Ken and Matteo who will each provide a summary and status update of the data associated with observations from our ongoing Phase 1 trials of CUE-101, as well as the recently initiated CUE-102 trial. Following Ken and Matteo, I'll provide an overview of our corporate strategy and additional pipeline expansions within the CUE-100 series. Kerri will then provide a brief update of our financials, after which I'll return for closing remarks and then open up the call for a Q&A session. With that, I'll now pass the call over to a Anish.

Thanks, Dan. I'd like to start today's presentation by reminding folks of the genesis of our company's quest and the mission we seek to accomplish. Our mission is to address a very fundamental and consequential question for immunotherapy, which is, can we selectively and specifically activate anti-tumor T-cells, while avoiding the carpet bombing of the immune system to maximize efficacy and minimize toxicities. This is a very basic yet fundamental distinction from how other may be approaching the challenge of turning the immune system against cancers. To accomplish our objective, as shown in Slide 4, we envisioned exploiting the one unique marker of an anti-tumor T-cell, which is the tumor-specific T-cell receptor or TCR. We have engineered an innovative biologics platform termed Immuno-STAT, that generates TCR selective engages to deliver immune activating signals to tumor-specific T-cells. The figure on the left in Slide 4 depicts the core structure of an Immuno-STAT, which is essentially an antibody FC-based biologic containing stabilized tumor peptide HLA molecules to selectively target tumor-specific T-cells, along with desirable activation signals that are consumed by those T-cells. This framework provides a molecular basis for improved specificity for anti-tumor T-cell activation, while minimizing off-target toxicities due to systemic immune activation, which by the way, it continues to be a key impediment for many other broadly targeted immunotherapeutic approaches. On the right side of this slide, you can see a figure depicting the CUE-100 series, which is designed to selectively deliver IL-2 to tumor-specific T-cells over a relevant T-cell, hence generating a therapeutic index for IL-2 which as of yet has been a challenge. We believe this is a superior approach for harnessing the fullest potential of IL-2, especially since the tumor specific T-cells are present in a very low frequency. Our current clinical candidates, namely CUE-101 and CUE-102…

Thanks, Denise, and good afternoon to all listening to this call. We're excited to be presenting our updated data from the ongoing CUE-101 Phase 1 trial as both a single agent monotherapy and third-line and beyond head and neck cancer, as well as the encouraging emerging early data from the combination study with pembrolizumab in first-line patients. As previously and consistently stated, we believe CUE-101 Q1 mechanism of action is evidenced by the ongoing data generated to date provides effective and tolerated dose levels enabling selective stimulation of tumor specific T-cells. Recurrent head and neck cancer is a tough incurable disease. The data we have observed throughout the monotherapy trial enhances our confidence that CUE-101 is stimulating cancer specific T-cells in a subset of these patients with a resulting anti-tumor effect. Furthermore and more importantly, we continue to observe an evolving trend of enhanced survival. And while this data is still maturing, we are encouraged by the observations to date. Clinical observations beyond overall response rate and median overall survival continue to bolster our confidence in the anti-tumor effect in CUE-101. For example, we have observed patients experiencing tumor reduction after prolonged periods on drug where no [resistance] (ph) based objective response was initially observed by imaging. This observation consistent with observations made by other demonstrates the kinetics of T-cell anti-tumor activity that manifest over a longer period of time. This pattern can be seen in the tumor measurements plotted out on Slide 6 for a patient receiving CUE-101 at 2 mg per kg where we can see that the first several months appear to demonstrate tumor growth even beyond the 20% threshold used by resist criteria. However, we -- based on the overall clinical status, the patient was continued on treatment after we changed the protocol to allow this. So after approximately six months the tumor began to shrink and the patient remains on therapy 14 months after starting treatment with CUE-101. The data presented on Slide 7 from a patient treated with RP2D at 4 mg per kg demonstrates stable disease lasting close to 12 months and ongoing with sustained reductions of cell free HPV-DNA, a biomarker that may reflect disease activity in patients with HPV-positive cancers. And in fact, this is a test that is increasingly being used by experts to guide treatment in these patients. This may represent a pattern suggestive of a pathologic CR. Taken together, these data build our confidence in the therapeutic potential of CUE-101 and in the potential path forward for registration study as a monotherapy in patients that have failed prior chemo therapy, as well as checkpoint inhibitor therapy. We plan to present additional data at an upcoming medical meeting. I'll now turn this over to Matteo to talk more about this and our other data. Matteo?

Thanks, Ken. The goal in our CUE-101 monotherapy study was to first prove safety for this first in man biologic, and second to prove that we could demonstrate activity. In addition to the data just described by Ken, we have observed in our 20 treated patients at the recommended Phase 2 dose in our monotherapy trial, one PR and seven patients with durable stable disease for an overall clinical benefit rate of approximately 40%. The next slide, Slide 8 shows the patient with a PR and they're supporting pharmacodynamic metrics. This heavily pre-treated patient has completed 17 cycles of CUE-101. You can see in the two upper right panel that the patient demonstrated a nine-fold increase in cancer specific T-cells, but did not demonstrate an increase in the general CD8 positive T-cell population, which might cause unwanted side effects, including immune related adverse events. The patient also demonstrated a transient and modest increase in Tregs that return to baseline by day 15. Patient demonstrated a sustained increase in NK cells, a positive attribute for an anti-tumor response as the NK cells may assist in tumor killing. We observed similar pharmacodynamic effects across many patients. On the lower right portion of the slide is a graph showing a rapid decrease in circulating cell-free HPV DNA, corresponding with the decrease in tumor burden observed by imaging. We had made the same observation with several other patients who have demonstrated antitumor activity and continue to monitor cell-free HPV DNA as a possible predictive biomarker. The next slide, Slide 9 conveys our ongoing survival [swimmer] (ph) plot for the 20 patients dosed with the recommended Phase 2 dose of 4 milligrams per kilogram. We have taken the liberty to draw a median overall survival line at eight months, which is reflective of the median…

Thanks, Dan. Turning now to Slide 16, I'd like to provide a brief update on our financial results for the three months ended June 30, 2022. The Company reported collaboration revenue of approximately $26,000 and $2.7 million for the three months ended June 30, 2022 and 2021, respectively. Research and development expenses was $9.6 million and $8.8 million for the three months ended June 30, 2022 and 2021, respectively. The increase was primarily due to an increase in laboratory and drug substance manufacturing costs, as well as clinical expenses related to our CUE-102 Phase 1 dose escalation clinical trial that was initiated during the second quarter of 2022. General and administrative expenses were $3.8 million and $4.3 million for the three months ended June 30, 2022 and 2021, respectively. The decrease was due primarily to a decrease in stock-based compensation and professional and consulting fees incurred during the second quarter of 2022 as compared to the same period in 2021. We ended the quarter with approximately $66.1 million in cash and cash equivalents and working capital of approximately $60.7 million. Importantly, we took proactive steps to decrease the company's office and lab footprint and restructure specific functions, which will afford us significant cost savings that can be allocated to our clinical programs. We believe our cash and cash equivalents as of June 30, 2022 will allow us to support the development of our Immuno-STAT platform, including the clinical development of CUE-101 and CUE-102 through the through the third quarter of 2023. I'll now turn the call back over to Dan for closing remarks. Dan?

Yeah. Thanks, Kerri. As you've heard on this call, we continue to execute and make significant progress towards further advancing our lead and representative candidate CUE-101 towards a potential path for registration. And through the clinical development of 101 we've clearly demonstrated the ability to selectively target and activate defined anti-tumor T-cells, while not compromising patient safety. As seen on Slide 17, we have successfully executed and continue to execute on defined strategies providing risk reduction and validation of the CUE-100 series and its derivatives. As such, CUE-101, which is targeting the HLA-A02 allele has clearly demonstrated tolerability and single agent activity. And remind you, with no maximum tolerated dose emerging from the dose range of 0.06 mgs per kg, all the way up to 8 mgs per kg. We've seen clear evidence of pharmacodynamic effect on targeted tumor specific immune cells, that is T-cells as well as natural killer cells, obviously, the properties that we want to see in the immune compartment. Clinical activity demonstrated from 1 mg per kg to 4 mgs per kg with 4 mgs per kg being our recommended Phase 2 dose. And clear evidence of anti-tumor activity, which we've gone through some of these data showing of a prolonged effect having to do with the kinetics of the stimulating the immune system, immune system then dynamically interfacing with cancer. So clear evidence of that anti-tumor activity manifested as a confirmed PR, seven durable longstanding stable disease with one potential pathologic complete responder that Ken reviewed. Also we appear to be providing a survival benefit, this obviously needs to be determined as to what the median overall survival is, but it is clearly trending in a positive direction, and we believe it will provide us with a potential path forward for registration. 101 in combination…

At this time, we'll be conducting a question-and-answer session. [Operator Instructions] Our first question comes from the line of Stephen Willey with Stifel. You may proceed with your question.

Yeah. Good afternoon. Thanks for taking the question and thanks for the update here. With respect to the updated CUE-101 data, do you have a median duration of treatment at this point? I think it looks to be about two months just in terms of eyeballing it, but just wanted to know if that's correct? And then also, can you just broadly speak to post-study therapy that these patients may or may not be receiving following discontinuation of CUE-101and I guess your confidence that post-study therapy is not impacting extended OS time that you're seeing off treatment? And then I just have a quick follow-up on CUE-102.

Okay. Thanks, Steve. Ken, you want to take those questions?

Yeah. Hi, Steve. So the median therapy is two cycles, meaning half the patients got two cycles and came off. I would just point out that that's basically the same as second-line, we see what second line checkpoint inhibitors is. So it really comes down to what did those patients do as far as overall survival, because the progression-free survival just doesn't correlate as you know. As far as follow up therapies, we are still collecting that data and really don't have that to report yet. We do know some patients they haven't -- that are doing quite well off all therapies. So we just don't know that data yet. Sorry.

Okay. And then just on CUE-102, I know that dose escalation portion and presumably expansion is requiring WT1 antigen positivity. Is this just kind of like a binary yes/no type of assay that's, I'm guessing, IHC-based or is there some kind of graded expression that a clinic needs to have in order to be eligible?

Yeah. It is IHC-based and it is grated, but our sort of minimal requirement is that 1% of the tumor cells are expressing WT1.

Okay. I'll hop back of in the queue. Thank you.

Our next question comes from the line of Reni Benjamin with JMP Securities. You may proceed with your question.

Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress. Maybe just starting off, can we talk a little bit more about the biomarker data that you generated. I see the circulating -- sorry, the HPV-DNA going down considerably better, and then -- but the tumor shrinkage is occurring, but not clearly as much. And I think you may have called out a pathological CR. I'm not too sure if I understand how well that's being correlated. And so can you talk to us a little bit about that? Would you use that going forward? And what other sorts of biomarker activities are you planning for these studies, both for 101 and 102?

Okay. Ken, you want to take the first part of that and then have Matteo cover the second half.

Yeah. So essentially, what we're seeing is that, we have several patients with durable stable disease. And as you know, with the immunotherapy types of therapies, the IO type therapies, you often can see sort of a stabilization of disease that could be scar, it could be fibrotic tissue, it could be inflammatory tissue and we had the -- early on, we had the patient at 1 mg per kg who had stable disease and we ended up going to the operating room and seeing that patient and never has remained off therapy for now 14 months or 19 months. And then the data that we've been getting from these ongoing cell-free DNA assays, which didn't really exist when we started the trial, was that several of our TIs have started to follow virtually all of the patients with cell-free DNA to try and get some insight into their disease, especially when we don't know when somebody has an increase in their tumor, if that’s by resist, if that's more I resist, is that an inflammatory change that we should be following, what their cell-free DNA, is that going up or going down, suggesting it might be more inflammatory or with these stable disease patients do they have any active tumor left. And so, the data we talked about with this one patient who has very stable disease and the tumor is either just sitting there or what we think is not viable tumor is just sitting there like a scar and there cell-free DNA is zeroed out. So that suggests to us based on the other patients that that may be a pathologic CR if we took that out. And that is -- this whole area is evolving, especially in the head and neck cancer and our investigators are learning how to use cell-free DNA. It's not an accepted biomarker of response by the FDA by any means. But that's why we're trying to really figure this out and learn this and we are -- we don't have all the cell-free DNA back yet the data because we do and in batches. So we're very encouraged by it as a biomarker as our all of our docs, and we're going to continue to follow that and use that as a potential. We are talking about with one of our investigators in fact about doing an adjuvant study based on cell-free DNA responses in patients. I'll stop there and let Matteo talk about what we're doing with WT1.

Thanks, Ken. I believe that the questions have been well addressed at the point. I did want to add one comment regarding the previous question on the WT1 assay. Although we do use a binary results for eligibility, I just would add that we are paying very close attention and tracking both the nuclear inside of plasmic expression of WT1 by grade, so that we can correlate this data with potential patient outcomes.

And sorry, just kind of sticking with this thing for a second, are you seeing the converse accrue in that once patients are kind of progressing or off the study. Are you seeing HPV DNA – cell-free HPV DNA pick up in those patients as well or do they consistently stay low all the way through?

So, good question. What -- we don't have cell-free DNA on the patients after they come off study. We just are following them for survival and whatever therapies they have been on, et cetera. But what we can see is in patients who do progress there cell-free DNA actually will go up also. It's roughly correlates with tumor burden so we -- over it's dynamic, but that's why we're still learning about it as a biomarker, but we don't see people are truly progressing their cell-free DNA it does go up.

Yeah. I’d add as well, Ken, that this is an endpoint in the biomarker assessment that is gaining traction with FDA over the last 12 to 18 months. Whereas, it may be possible in the future to use it as a secondary endpoint and actually use it to inform decisions and adaptive trial design, but it's really not there yet. So that would an opportunity in the future to introduce that biomarker to sort of accelerate or perhaps enhanced decision-making in the next trial.

Got it. So second question is, when I look at the overall survival curves that you have, there are clearly those patients with durable FD, some obviously with partial responses. And then there are those that clearly have progressed. I mean they are surviving, right, but there -- I'm assuming that these that don't have a durable FD marker [indiscernible] their tumors are growing. And I guess the question I have is, have you guys been able to investigate what sort of mechanisms of resistance might be occurring? And as you think about that, what sorts of combination therapies are you thinking about that could maximize 101’s durability going forward?

Well, that’s the $1 billion question, it's a great question. We honestly don't know of the myriad of resistance mechanisms, which ones are at play. What I think is caught us, certainly surprise early on and caught all of our docs by surprise early on is, are these durable overall survival in these patients that are even have come off therapy fairly soon. I think obviously when we're increasing the number of cancer specific T-cells in the periphery and then the tumor itself, we're allowing for checkpoint therapies to work better. Certainly, we've seen some early indications of potential antigen spread which would suggest that combinations with further cytotoxic types of therapies that are going to increase neo-antigens to be seen by T-cells is certainly something that we'll consider in the future. As far as other mechanisms like HLA down-regulation, et cetera, we just don't know yet, we don't have that data, may be Anish wants to comment on this, but clearly we think there's going to be synergies. The obvious ones with checkpoints as well as with chemo.

Yeah, the only thing I'd add, it's a really important question, Ren, we have to look at these analysis. There has been all the way from operational resistance pathways because of the [TME] (ph) to cell types, to even the tumor intrinsically changing its immunogenicity profile, whether it is because of loss of HLA or loss of sort of components of antigen processing. We just need to sort of get a better grasp on this and that -- as a part of the ongoing analysis certainly enough in a sort of line of sight, we just need to gather the data and that will then dictate what possible other combinations can we bring in along with CUE-101 to further sort of extract even more benefit than what we've already started to see.

Got it. And just one final one for me. I probably missed this in the prepared remarks. I remember, we were talking about a neo-adjuvant study for quite some time and primarily what gotten me most excited about was the ability to have biopsy samples kind of before and after. I just wanted to get an update as to what was happening with that study.

So I'll give -- I'll make a few comments and then I'll probably turn it open turn it to Daniel to add on. So that study is going quite well at [indiscernible] when we've actually already recruited our first couple of patients, we got the biopsies in place, we've got plans in place to get a composite batch analysis going as soon as a few more patients are recruit, that's in locally advanced head and neck cancer, Matteo, please feel free to add more to it from your lens.

Thanks, Anish. That's really quite accurate. We've treated a bit more than a few, and we look forward to sharing the data in the future when it becomes available.

All right. Thanks guys.

Okay. Thank you.

Thanks, Ren.

[Operator Instructions] Our next question comes from the line of Mark Breidenbach with Oppenheimer. You may proceed with your question.

Hey guys, good afternoon and thanks for taking questions. Just a couple from me. First, with respect to upcoming interactions with the FDA, is the plan right now to have the end of Phase 1 meeting in conjunction with the availability of MLS data from your Phase 1 trial? And when can we kind of expect to hear their perspective on regulatory path forward? And then I guess I'm also just wondering why there looks to be kind of a gap between the availability of MLS data and the potential start of the registrational study? So that's one question for me. And the other one is just with respect to the CUE-102 trial. Does this protocol include a paired biopsy collections? I know that wasn't something that was included in the head and neck study. I'm just wondering if any changes have been introduced so we have more translational data from the CUE-102 patients.

Okay. So Ken, you want to take that?

Yeah. Sure, I can start with the question regarding the interaction with the regulatory agency. So as we've just covered here, we anticipate having a mature median overall survival data by the end of the year in the 20 patients dose at the recommended Phase 2 dose and we have designed a Phase 3 trial that we plan to present to FDA in the context of a subsequent registrational trial. And again, we're beginning to do preparations for such an trial at risk and anticipate that we could begin open that trial, which would be a global multi-regional trial sometime later next year.

[indiscernible] biopsies as well in the WT1 trial.

Yes. So we have -- you're absolutely correct. So we have made in the protocol paired biopsies optional. We've had a lot of productive conversations back and forth with investigators and we recruited some that are keenly interested and capable of arranging those. So we hope that in the tumor indications that we're enrolling in the 102 trial will have the opportunity to get paired biopsies perhaps in atomic locations in these indications that may be, if you will, more [indiscernible] and amenable to biopsy. But to your question, it is an optional procedure at this point, whereas in the new adjuvant trial by design we have an opportunity to examine pre and post-dose biopsies as a component of the patients interventional standard of care in the setting of locally advanced cancer that's undergoing resection with curative intent.

Okay. And just going back to the regulatory question. I just want to be absolutely clear, we wouldn’t hear until 2023 a regulatory feedback with respect to what a registrational trial might look like in head and neck cancer, is that correct?

I think that's correct. And I would say early 2023, of course, some of the interactions will really depend upon the timelines granted by FDA. But in this setting we're confident that requesting a Type B meeting request, but given where we are in the development that FDA would agree and be collaborative. So it's not to drive the potential of the development for this drug in this unmet medical need in third-line patients and beyond with head and neck cancer.

Okay. Thank you so much.

And -- this is Ken, we certainly I think the end of ’23 is our conservative estimate. We are -- we know what that trial, we want that trial to be -- as soon as we get the data we will be ready to go and hopefully be able to launch sooner at this point.

Got it.

Ladies and gentlemen, we have reached the end of today's question-and-answer session. I would like to turn this call back over to Mr. Daniel Passeri for closing remarks.

Okay. Thank you very much. I want to thank the research analysts for questions, very helpful and instructive. I just want to thank everyone for listening in and your ongoing interest and support of our activities and bringing these very promising therapies to patients. So thank you very much. Take care. And we look forward to providing updates throughout the year. Take care.

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation. Enjoy the rest of your day.