Thank you for standing by. This is the conference operator. Welcome to the Cue Biopharma Second Quarter 2020 Earnings Call. [Operator Instructions] I would now like to turn the conference over to George Zavoico, Vice President, Investor Relations & Corporate Development. Please go ahead.

Thank you, and good afternoon everyone. Thank for joining us on today’s investor and analyst update call. Joining me on the call today are Dan Passeri, Cue Biopharma's CEO; Dr. Anish Suri, President and Chief Scientific Officer; Dr. Ken Pienta, Acting Chief Medical Officer; and Kerri-Ann Millar, Chief Financial Officer. Before we begin, I would like to remind you that during today's call, the Company will be making forward-looking statements. Various remarks that the Company makes during this call about the Company's future expectations, plans and prospects, constitute forward-looking statements for the purposes of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by the forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of the Company's Annual Report on Form 10-K filed with the SEC on March 20, 2020, and Quarterly Report on Form 10-Q filed with the SEC on August 07, as well as other filings made by the Company to the SEC from time to time, which can be accessed on the EDGAR database at www.sec.gov. In addition, any forward-looking statement represents the Company's views only as of today, August 31, and should not be relied upon as representing the Company's views as of any subsequent date. While the Company may elect to update these forward-looking statements at some future point, the Company specifically disclaims any obligation to do so even if the Company's views change. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to today. Please be advised that today's call is being recorded and webcast. The slides we are presenting today and a recording of our call will be available on our website for the next 90 days. We will also be available via the email provided on our website for questions unaddressed during the call. I would now like to turn the call over to Cue’s CEO, Dan.

Yes. Thanks, George. Good afternoon, everyone, and thanks for joining us today for a review of our ongoing progress and second quarter financial results which are available in more detail in our Form 10-Q filed with the SEC on August 07. Also to remind everyone on the call, as we proceed through the call, the slides may be advanced directly from your computer. So the next slide on slide three, shows our agenda for today’s call. I’ll provide a brief synopsis and overview of our pipeline emphasizing the importance of datas emerging from our lead program CUE-101 representative of our breakthrough approach for the selective modulation of disease relevant T cells directly in the patient’s body. I emphasize breakthrough because we believe we are on the cusp of demonstrating that CUE-101 is and which is representative of our CUE-100 series is capable of presenting a tumor-associated antigen directly to the targeted T cell receptor or TCR together with a [Indiscernible] cytokine in this case IL-2, specifically and selectively to selectively activate or to safely activate only disease relevant T cells directly in a patient, to elicit a clinically meaningful response without dose limiting off-target adverse events. I’ll be followed by Dr. Ken Pienta who will provide further details on our most recent observations from our on-going Phase 1 CUE-101 monotherapy dose escalation and expansion trial in HPV positive head and neck cancer patients. Then Dr. Anish Suri will describe our continued innovation and additional progress that we’ve made in advancing our differentiated Immuno-STAT and associated Neo-STAT platforms. Anish will also highlight our expanding Immuno-oncology pipeline including the continuing progress with our CUE-300 program in collaboration with Merck. The progress we've made with our on-going Phase 1 trial with CUE-101 and additional programs, particularly throughout the challenges of the on-going COVID-19…

Thanks Dan. And I'm excited to be talking to everyone this afternoon. I’d like to again remind everyone about the tremendous commitment we have from the participating clinical centers, and associated oncologists shown here on slide five. Throughout the COVID-19 pandemic, this group of highly respected and dedicated oncologists have remained focused upon screening and enrolling HPV-16 positive head and neck cancer patients to participate in our trial, as evidenced by the full enrolments of Cohort 4 and Cohort 5 since our last earnings call in May of this year. Through our pre-screening process, we continue to identify patients for our trial for future cohorts. Slide six shows a high level summary of the design for on-going Phase 1 trial CUE-101. As a reminder, we are enrolling second line and beyond patients with recurrent or metastatic head and neck squamous cell carcinoma driven by HPV, specifically HPV-16. This represents approximately 70% of all head and neck cancers occurring in the oropharyngeal region, accounting for an estimated 13,500 patients annually in the U.S. alone. With our precision medicine approach, this Phase 1 trial to find molecular inclusion criteria to include head and neck cancer, cancer patients that HLA-0201 positive, and whose tumors are confirmed to be driven by HPV-16. Through these specific inclusion criteria, we are ensuring that only patients with the potential for clinical benefit are enrolled and treated This trial was designed with the primary endpoints of safety and tolerability, while concurrently defining the PK parameters of CUE-101, the secondary endpoints of PD evidencing the drugs mechanistic activity and T cell activation and proliferation, as well as assessing signs of clinical activity, activity via periodic patient scans. The trial is a standard two-part trial with the first Part A designed as a typical 3+3 monotherapy dose escalation, patients who…

Thanks, Ken. And thank you to everyone listening in, and I hope all of you and your families continue to be safe and well. I'd like to underscore on slide 11, our scientific vision to fully exploit the exquisite selectivity and specificity of the immune system while not compromising patient safety. We believe this approach for selective modulation of T cells directly in the patient is distinct and differentiated from other approaches where in broad immune modulation or global systemic activation often present with significant challenges associated with compromise safety, compromised efficacy and tolerability. The Immuno-STAT framework as exemplified by the CUE-100 series, as shown in slide 11 contains the two key signals. Signal 1 and signal 2 for tumor specific T cell activation. CUE-101, our lead clinical candidate is our first drug from the CUE-100series. Signal 1 here on the CUE-100 series consists of stabilized peptide MHC molecules to engage tumor specific T cells via the T cell receptor or TCR, thereby locking in the specificity combined with rationally engineered IL-2 molecules serving as a cause to military signal 2 that selectively act upon those T cells to control their activation directly in the patient. There are two modifications to our IL-2 variant molecule that are important for its specificity and selectivity. The first is abrogation of binding to IL-2 receptor alpha subunit in order to avoid Treg engagement, which labels it as a non-alpha IL-2 variant, the second is attenuated binding to the IL-2 receptor beta sub-unit such that the IL-2 activities biased to those T cells that are docked to the specific peptide HLA complex via their T cell receptors as perhaps best shown at the top down view of the CUE-100 series framework here. Now, we've invested considerable time and effort to define this molecular framework…

Thank you, Anish. Turning now to slide 18. I'd like to provide a brief update on our financial results for the second quarter, ending June 30, 2020. We finished the quarter with approximately $84.9 million in cash and cash equivalents and working capital of approximately $73.5 million. During the second quarter of 2020, we extended our cash runway with $42.4 million of our aftermarket equity offering with Stifel Nicolaus & Company, who acted as sales agents. Cash received from the ATM equity offerings with Stifel put us in a solid financial position to support the development of our Immuno-STAT platform, including the clinical development of CUE-101 into 2022. We recorded collaboration revenue of $1.1 million from collaboration with Merck and LG Chem during the second quarter of 2020, which is consistent with the $1.1 million we recorded for the same period in 2019. Research and Development expenses were $8.1 million for the quarter ended June 30 2020, as compared to $6.9 million for the same period in 2019. This increase in R&D expenses was due primarily to an increase in laboratory and drug manufacturing costs, but stock based compensation and clinical expenses. These increases were offset in part by a decrease in travel expenses due to the COVID-19 pandemic which hampered travel throughout the second quarter. General administrative expenses were $3.9 million for the quarter ended June 30 2020, as compared to $3.4 million so the same period in 2019. This increase in general and administrative expenses was primarily due to an increase in stock-based compensation expenses, and legal and accounting fees incurred in the second quarter of 2020. I'm pleased to say that despite the challenges presented from the COVID-19 pandemic, we've been able to maintain momentum in the -- and development of our pipeline while strengthening our financial position through a combination of aftermarket equity offerings, and disciplined spending. We continue to be well positioned to execute against our 2020 objectives. I'll now turn the call back over to Dan for closing remarks. Dan?

Thanks, Kerri. Since our last update call, and despite these on-going challenges, that we're all confronting due to the COVID-19 pandemic, we've continued to make significant progress across our platform and associated programs as I'm showing here in slide 19. Our key accomplishments include the on-going timely enrollment through cohorts, 1 to 5 and now into cohort 6, which is at 4 milligrams per kilogram, and our CUE-101 monotherapy trial and the demonstration of favorable safety and tolerability through cohort 5 at 2 milligrams per kilogram dose proportional exposure, which is -- has been in line with our preclinical projections, and emerging evidence of PD activity and early signs of monotherapy clinical activity. Having raised additional capital this past quarter, and having enrolled and treated patients into cohort 5 and our Phase 1 trial of 101, our lead program, we're very well positioned to continue building a meaningful body of data including safety, tolerability, PK and PD biomarkers activity, as well as on-going scans from patients to assess clinical activity. We're also advancing closer to determining a recommended Phase 2 dose for CUE-101 as a monotherapy and to initiate a combination trial, with KEYTRUDA in October, and a neoadjuvant trial, beginning end of year or Q1 of 2021, both and newly diagnosed and previously untreated patients in head and neck cancer. These data would significantly de risk and validate our approach, allowing us to then further build our pipeline based on the same foundational principles upon which we brought CUE-101 forward and to establish Cue Biopharma as a differentiated leader in the immunotherapy space with a potentially transformative and disruptive breakthrough therapeutic platform. Our guidance for the second half of 2020 milestones is shown in slide 19. And they are largely unchanged from our last call are reporting PK/PD results…

Absolutely. [Operator Instructions] The first question comes from Stephen Willey from Stifel. Please go ahead.

Yes, good afternoon. Thanks for taking the questions and congratulations on the progress. Of the six patients that you talked about remaining on therapy, I think three cycle four, three cycle five, are you able to say, I guess how many cycles on average those patients have seen? Are they beyond cycle two? Are they in cycle three? I guess any color on that front with respect to just kind of treatment intensity would be helpful?

Yes, and so the patients are still relatively early there. You know, past the cycles of cohort four folks are beyond cycle two, and just in one of our cohort five patients is beyond the cycle beyond -- cycle two at this point. So it's still relatively early in the process for these guys, for these patients.

Got it. Got it. And then just with respect on or, or with respect to the expansion of the peripheral T cells that you're seeing. I know it's maybe not the best of surrogates and it sounds like you may have some data coming out to suggest that perhaps the real impact is happening within the tumor microenvironment itself with respect to direct engagement of TILs. But is, is that day 42 metric of T cell expansion that is being shown? Is that a pre dose? Or is that a post dose level? And I guess if it's the latter, is there any interest in trying to do a little bit more refined peripheral blood draws between doses just in an effort to maybe better understand what the persistency about expansion in the periphery might look like?

Yes, that's, that's great.

No, I was just gonna, I'm just gonna jump in here.

Go ahead Anish.

Sorry. Just Steve, just to clarify that was post those analysis. And rightfully, and I think this is what Ken was getting to as well that one of the sample time points is the challenge here because these are all 21 days apart. So what happens after you give the drug in the interim time and if there is extravasation to the peripheral lesion tumor tissues is exactly what's not measurable here? And to what Ken alluded to, the neoadjuvant study becomes very important to study that mechanistically. So one of the limitations of course, here is that limited availability of tumor tissue to be able to quantitate that. I think the paper that we presented from our clinical cancer research and this publication, that's impressive. I'm making a very important point, which is that what ultimately matters in immunotherapy is what happens locally. The peripheral is a good surrogate for the mechanism, as you will alluded to Steve, but ultimately what we're missing here is that final piece in the puzzle, which I think the neoadjuvant gets us there. I’d let Ken comment on the sampling frequency and again, in the current times to help us we'd navigate to that.

Yes, I was just going to add that, we will, as we learn more and more about, you know, the PD and sampling, we have thought about expanding quite to be quite honest. Right now, we're limited by COVID in that most of the sites and hospitals don't even want the patients coming in for any extra blood draws. But we're constantly monitoring how to, potentially get more data. For example, we're exploring using mobile phlebotomy to try and fill in some of those future data points. Especially we're thinking hard about that and as we start the combo trial in October, you know that if COVID is still going to be a problem, which is likely that it is going to be we really feel that, we need to be able to have be as nimble as possible in collecting samples. I think you all have noticed that we have done what I've continued to be as a medical oncologist amazed by is our ability to accrue patients on time through this COVID crisis. And I'm humbled by the fact that my medical oncology colleagues have considered it's so important to that, to administer CUE-101 to these patients that they've managed to keep our trial open and accruing. It is a challenge, though, once we get them into to get those extra blood draws that we'd all like to see, again, to decrease exposure of the patients to the risk of COVID. And that's why we're, exploring other options to help us fill in those data points in the future. So that was a bit of a long winded answer, but I hope that helped.

Yes, that was very helpful commentary. Thank you. And I guess just lastly for me, you talked about now being able to start at a higher dose of CUE-101 and the KEYTRUDA combo study. Are you able to say what that target starting dose will be?

Well, what I can say is, it's on -- we're on-going to and analyze where we'd actually like to start initially. For example, we were thinking we'd have to start a cohort 3 at 0.54 mg/kg. But really, what we're planning on doing is starting at a safe dose minus one. So currently, that are you know, we'll start at a mg/kg. And we may or may not go to 2 mg/kg depending on where we are with accrual in cohort 6 at that time. So right now we're at a mg/kg.

Right. Thanks for taking the questions.

Thanks, Steve.

Thanks. My next question comes from Madhu Kumar from Baird. Please go ahead.

Hey, so first questions on…

Madhu, you’re breaking up a bit difficult to understand. Operator may be getting worse. Yeah, we're not able to catch you. Operator, maybe we can take another question in sequence and then put Madhu back in.

Our next question comes from Tom Shrader from BTIG. Please go ahead.

Good afternoon. Not surprisingly, I think I have almost the same questions as Steve. Can you let us know your longest stable diseases so far? I guess these are from cohort 3. But what are the longest couple you've seen?

Ken, you want to take that?

Yes. So our longest couple have been 19 weeks, and we had one patient that had a break in therapy with the BP and that was about a total of 12 weeks.

And are they both still on therapy?

No.

Okay. And then kind of question for Anish. This patient 10, I assume that's a pretty good response. Is that consistent with a memory response to you, the time course? Can you dig any quantitative data out of there between what happens between day 21 and day 42? Or is this somebody building kind of a response from naive T cells? Is that something you can dig out a data like this?

Yes, I think Tom look, firstly, these are early metrics. So the data looks promising, we need to build this out a bit more. If you were to compare this to an established chronic, sort of a memory repertoire against viral determinants like CMV or EBV. This would not be as robust as that. And the fact is, even with, if you look at the staining pre dose, you don't really see much of a population. So you could say maybe there was something there but at really rare frequency and it took a couple of cycles of treatment for it to present itself, or the likelihood is that it's being primed from a naive baseline repertoire. Hence, you need the additional sort of time on therapy for it to manifest and present itself. I think that's how we interpret it as this being either a rare or from a non-prime simply because of the fact that as baseline, you don't see that population if you -- control view. In contrast, if you look at, for example the data with CUE-102 in that example, that we presented Tom, I mean, there you could see a little bit of a pre dose, pre population that's present at baseline in blood, which then further expanded out. So this is, these are rare T cell frequencies, we know that. They are usually not easily detectable in patients and the fact that we start to see them is what's very encouraging and promising and that's exactly the building out on the going up and the dose and escalation and exposure to see if we can further solidify these metrics.

And then maybe if Ken could just comment on, does that change the way you think about a trial like this, if you are really going to need eight weeks to see a response?

Yes. So, I think we're we all recognize that these patients are sick, right? I mean, they've got rapidly progressive disease; they've had multiple lines of therapy. And ideally, we will move to earlier treatments. I think that's what makes the combo study, so important. Because those patients will have be first line therapy patients and that gives, makes me optimistic that we'll see even better responses and they have more time to see those responses. It also makes me think about whether, in the future as we think about other diseases, certainly, again, the less heavily pre-treated patients, the better. And so I really am optimistic and continue to be optimistic about the first line therapy patients and as well as even the neoadjuvant. So, as you well know, in these Phase 1 studies, first in human studies, first and foremost, it's safety, safety, safety, and anything we can see clinically is a huge is a huge win.

Got it. Thank you for the details.

Hey, Tom, just to clarify, just an add on again. I wouldn't look at it that it takes eight weeks for response because one of the things coming back to the point we discussed with Steve was the fact that in the tumor lesion is something that has not been quantitative. So while these are peripheral signals, if you've got a presence that is extravasated, low close to the tumor, the drug is getting there, which is why there's important paper coming out, it's very important. Then that effect may well be very central to the response but not being fully appreciated by just a blood analysis. I always want to put that caveat, which is why I come back and what Ken articulated very nicely is the importance of the neoadjuvant study to get this to really delve deep into that mechanistically.

Yes, got it. Thank you.

Our next question comes from Reni Benjamin from JMP Security. Please go ahead.

Hey, good afternoon, guys. Thanks for taking the questions and congrats on all the progress. I guess some, maybe just to start off with a question for Anish. Hopefully you can hear me okay. Selective, we keep focusing on the selective population of T cells expanding out. And I'm kind of curious, what other metrics outside of the selective T cells should we be looking at or, be measuring? For example, maybe cytokine levels, or CDA and CD4 T cell ratios. What all are you -- are you gathering that might be able to help kind of complete the picture of what's happening here?

Yes, Ren the intentions are, you know, in parallel to look at Immunophenotyping for other subsets, like you pointed to. One of the cell types from our preclinical models is the activation and possible effects on encase, which could be something that could be favorable, they are highly sensitive to IL-2 even attenuated versions. We've not seen any consistent movement on Tregs, with sort of consistent data and that's in line. Other global up regulation of T cell subsets should not really happen by the molecular design. So, and that is, at least in these early data sets, that seems to be consistent. But I think, I think overall Immunophenotyping, and understanding other IL-2 from the periphery, is something we will continue to look at, and that data and will continue to be strengthened. We haven't looked at cytokines, we've, of course, -- samples, we'll come back to that as we sort of accumulate enough sampling and decide on time points. The other than being from a metrics of just immune recognition and effector mechanism. Again, coming back the tumor tissue becomes a very important composite of really what I referred to earlier. So the gold standard metrics and that in the monotherapy, where the biopsies have been optional is going to be limited, and again, if we can garner some of that through the neoadjuvant study that can describe I think that will further add on and in that modality, one could focus not only on the antigen specific, localized, but also repertoire, diversity, including effects and other immune subsets, which would be very telling to the mechanism of action.

Got it. And then when we think about, the kind of cohort 6 that we're going to be starting to enroll, or have started to enroll there's a significant amounts of dose kind of relative to the Proleukin dose, right. And of course he's continued to have a really good side effect profile. And I'm trying to maybe you can help me reconcile, is this a, is this a true reflection of the side effect profile of the drug or, or are the patient's immune status, and that weakened immune cell status and so I think Ken mentioned had four prior lines of therapy. Does that potentially impact what the side effect profile, is actually looking like? And in effect, are we masking the side effect profile, the true side effect profile given the patient's immune system status?

Yeah. Ken you want to take that one?

Yes, thanks. So that's a really interesting question. I think the best way to think about answering that and thinking it through is that, if you look at the IL-2 data of the Proleukin data in similarly, ill [ph] groups of patients. You saw, you didn't see an attenuation of the side effect profile of the toxicities at all of IL-2 of Proleukin. I mean, even in heavily pre-treated sick patients like, we're dealing with. The toxicity profile of Proleukin was very evident. So I don't personally believe that that's the core. The reason why we're, not seeing, a lot of grade three and grade four toxicities. I think it's because we really do have selective on target. We have a selective on target treatment. And so I would have, again Pro, the Proleukin patients really did have, a lot of side effects. You also saw that in the checkpoint inhibitors, when they -- when they, in the early trials, again, in the very advanced patients, you saw them have tremendous toxicities. So I don't think that, that idea holds up.

Got it. And I guess one final one from me. All this data that that you know, is being accumulated when do you think we might be able to see this in a scientific or publication form?

So when we have the clinical… Go ahead; go ahead, Ken, if you want to comment on the clinical data presentations later in the year.

Yes, well, I think we would typically not publish certainly a manuscript on this until we got through the Phase 1A and 1B, where we had total data, clinical PK/PD data on, all the patients that went forward to establishing the RP2D. I think we'll start putting out some abstracts and things, for example, at Citi and ASCO, next year, in between. But that, but the totality of the data we'll wait till the trials complete. And – but and we do have an abstract will be presenting it at Citi.

Great. Thanks guys for taking the questions.

Thanks, Ren.

Thank you Ren.

Our next question comes from Mark Breidenbach from Oppenheimer. Please go ahead.

Hey, good afternoon and congrats on all the progress with this escalation and also Kerrie congrats on the promotion. Two quick ones for me. Maybe, revisiting one of the questions from Tom, on the kinetics of T cell expansion you're seeing in patient 10. Obviously, probably two days seems maybe a bit longer than I would have expected based on what we saw in some of the preclinical models and I just want to be absolutely clear, Anish or Ken, if you're attributing the discrepancy in kinetics between preclinical and clinical data to the fact that we're looking at peripheral T cells only. And maybe in the preclinical models you were looking at tumor biopsies. Is that is that the right way of thinking about it?

Yes, I think Mark, there's a couple of things. In the preclinical models, you're not facing the headwinds of a compromised immune performance status. So these are extremely sick patients, as you realize. And so your starting baseline is a healthy, diverse repertoire, you can tap into whether whereas here, you know, obviously have the spectrum of patients that have been to multiple lines, and that's hard to decipher. I think in our own instances, there have been cases where we've seen it after the first cycle. And then in cases like this, where you know, it needs a bit more and that comes back to the question well, did the patient really didn't have enough that you had to prime and boost and that's what you're seeing here, that's what it's indicative. Or that they have something in a peripheral lesional site that you're not able to quantify? And I just put that out there as a variable, because we through much of the work in cancer immunotherapy reading things out in the blood. That's the one variable that is very hard to pinpoint when, again, coming back to the preclinical model that, the reason I showed you the data is if you look at it in blood in the preclinical models, is again fraction of a percent in the same animals where you had the response. And when you looked at the tumor lesions, that relative presence of a T cell repertoire that was enriched enormously. That we are obviously blind to hear in this scenario, we're always -- we've got a peripheral presence that we're using again and in fractions of a percent without knowing what's happening centrally. And that's again comes back to the importance of a study like a neoadjuvant where you have the pre and post mass with you to be able to really quantify and establish that relationship once for all.

Okay, fair enough. And I guess my second question is in relation to how you'll know when to stop -- escalation. So you go through cohort 7, it makes -- and you still are not seeing the DLTs? How do you really decide when to declare a recommended Phase 2 dose? You know what, why not consider going higher than it makes per [Indiscernible]?

Ken, you want to take that one?

Yes, thanks. So I think that we built this trial, and again, put on the Bayesian and approach over the top of the three by three design, specifically so that we could expand dose cohorts, up to nine patients so that we could explore clinical response as well as PD. Because if we don't hit a maximally tolerated dose, we have to choose the what are biologically effective doses. There's, there's no reason why we can't go to higher cohorts at all into higher doses. And we may consider that as we move forward. But again, that whole approach to really see if we can define a biologically effective dose by not just relying on three patients per dose level, and actually going up to nine will give us confidence that potentially that we are going to define a BDD when we don't see an MTD. So we really, I'm just so thrilled with this design, because it gives us this opportunity to find that effective dose, as we anticipated that we may be so safe that we can’t find an MTD. But that's the longer answer. The shorter answer is, we may decide to go to higher doses. We just -- we'll just see what happens.

Okay, got it. Thanks for clarifying. And congrats again. Thanks for taking questions.

Thanks, Mark.

Our next question comes from Madhu Kumar from Baird. Please go ahead.

Yes, hopefully this is better in terms of being able to hear me.

Yes.

Very good. Okay, great. So I'm really kind of coming back to a lot of questions that have been coming up during this call. If you put it all together, and think about the absence so far of RECIST responses with one-on-one monotherapy. To what extent do you all believe that's due to intervention dose of the drug to kind of refractory nature of the patient population or the absence of PD -- PD-1 PDL-1 blockade, or any kind of mixture of the three. How would you kind of rank those three in terms of and unlikely reasons why you haven't seen [research] responses so far?

Yes. So this is Dan, probably the least qualified to answer that kind of question. I'll give it sort of a broad overview and then I’m going to turn it over to Ken and Anish. So Madhu, a good question, great question. And it's probably all of the above in various aspects. This is a heterogeneous patient population. Very poor health condition, compromised immune system. Immune system has been basically circumvented by the tumor in various ways. So I think all of the above is probably at play in various degrees with this patient population. So the objective with the monotherapy is obviously primarily to show that the drug is well tolerated and safe, showing the drug like properties pertaining to its dose proportional exposure with PK, the PD effect. And as this conversation is obviously focusing on in the series of questions is tying all that into what's going on at the tumor level. We appear to be seeing metrics of clinical benefit. So the monotherapy, it's really dose escalating to the point where we see in a subset of patient’s clinical activity. And just to remind everyone in this patient population, if we see one patient out of 10, on average, with a RECIST criteria, partial response, that's extremely encouraging just based on historic performance with this patient population. So, we're going to be following this data clearly going into upstream into the front line with Pembro, I think bodes very well for the compilation of data we've already seen. But even with the monotherapy, we just continue to move forward with optimism based on the metrics that we've seen emerge today. So with that, I'll turn it over to the clinician who obviously oncologist knows a lot more about this than I do. Ken, do you want to elaborate?

Well, you did a great job of answering that. I think, I would turn it around and go. I'm amazed we've seen the amount of activity we've already seen. In fact, I think we've already as I mentioned, is on the call. We've already seen enough data to be confident to move forward into the combo study, because of the amount of activity we've seen. And I think it's just too early to expect more. It's just amazing to me that we've seen as much as we have already. And I'm so highly encouraged by that, we've got to pull the trigger on the combo, and as well as the neoadjuvant to get us even more, more data. I mean those are things we do unless we're really confident we have an active drug. So I'm not at all discouraged or somehow surprised that we haven't seen more. I'm actually surprised we've seen as much as we have.

Okay, so following from that if you see kind of better than PD-1 efficacy when you combine 101 with PD-1 and frontline, HPV16, positive head and neck cancer, would you revisit 101 monotherapy and they are kind of more early line proximal kind of right after PD-1 line of therapy to kind of address this issue of these sort of super late line patients not really being immunologically up for a new experimental agent. Like would we possibly revisit kind of a second or second third line therapy post PD-1 rather than you could have really lateline patients?

So yes, absolutely. I would point out by the FDA that we were constrained that albeit the patients in the monotherapy trial also had to see Platinum based chemo. And that's why, we have an average of four lines of previous therapy on all of these patients. I also think we'll be seeing the -- we'll be see what effects we have as a single agent, in there -- in the neoadjuvant study. So, I think we'll get started to get more hints about that as we move forward. But absolutely, again, short answer, absolutely yes.

Hey great. Thanks for taking our questions.

Thank you.

Our next question comes from Geo [Indiscernible] from Needham and Company. Please go ahead.

Hello everyone and thanks for squeezing me in there at the end. Congratulations on all the progress. So just a couple of questions. First on CUE-101the combo study, is this maybe you can clarify something, just think that pembro combination chemo had a higher response rate than just pembro by itself. Is there a reason to go with just pembro by itself or maybe due to the immunosuppressive effects of the chemo?

Ken, you want to take that?

Yes, so there is some – there is some data the data with chemo plus pembro. We wanted to again, as we move forward in trying to understand how our drug that works best. We thought it would be better and cleaner to and we're expecting great activity. So, we thought it would be cleaner and as did Merck, together with us think it would be cleaner and made the most sense just to do the dual agent combo, and that mix in with the chemo.

Alright. That next makes sense. And maybe a bit of a different question on the CUE-200 series. So these are some tumor necrosis factor, agonist. Is there any challenges associated with the structures and the trimerization that's required from these types of signals?

Yes, so we do a systematic sort of derivatization where we look at the sort of spacial relationship of the molecule, how it’s all sort of tethered together. And then we do a systematic extension, contraction of the various link or lengths, etcetera and we try to optimize the valences of where these receptors are on the T cell. So, we're not just putting these molecules together and seeing what happens. It's a very systematic study trying to sort of optimize the combination in terms of spacial relationship and how they engage with these, this sort of collection of receptors so that we don't have steric hindrance, and we have the optimal sort of resonance of valence -- of the valences, so that the signals are able to sort of align with each other based on that combination of factors. And all of that obviously plays into our intellectual property.

Alright, that makes sense, I mean, you definitely have the potential of using more than one by again on each antibody. So that might be some credibility there.

Yes.

All right. That's it for me. Everyone else got all the juicier questions early on.

Alright, well thanks. We really appreciate it.

This concludes the question-and-answer session. I would like to turn the conference back over to Dan Passeri for any closing remark.

Okay, thank you, operator. I again want to thank everyone for your on-going interest listening in. We look forward to providing continual updates. We're obviously entering a very exciting period for the company going forward. And everyone stay safe, and stay well. Thank you very much.

This concludes today's conference call. You may disconnect your lines. Thank you for participating and have a pleasant day.