Cue Biopharma, Inc. (CUE) Q4 2020 Earnings Report, Transcript and Summary

Greetings. Welcome to Cue Biopharma Fourth Quarter and Full Year 2020 Earnings Call. [Operator Instructions]. I would now turn the conference over to Dr. George Zavoico, Vice President of IR and Corporate Development. Thank you. You may begin.

Thanks, Sherry, and good afternoon, everyone. Thank you for joining us. On today's call are Dan Passeri, Cue Biopharma's CEO; Dr. Anish Suri, President and Chief Scientific Officer; Dr. Ken Pienta, Chief Medical Officer; Dr. Matteo Levisetti, Senior Vice President of Clinical Development; and Kerri-Ann Millar, Chief Financial Officer. Before we begin, I would like to remind you that 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 these 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 9, 2021, as well as other filings made by the company with 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, March 16, 2021, 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. Please be advised that today's call is being recorded. Live and archived versions of the event can be accessed via the company's website for the next 30 days. I'd now like to turn the call over to Cue Biopharma CEO. Dan?

Okay. Thanks, George. Good afternoon, everyone, and thanks for joining us today for a review of our ongoing progress as well as our fourth quarter and full year financial results, which are available in more detail in our Form 10-K filed with the SEC on March 9. Our agenda for today's call is shown on the next slide here at Slide 3. I'll first be providing a brief overview of our corporate objectives and program progress, and we'll then turn the call over to Dr. Ken Pienta, to provide a status update and review of our current observations from the ongoing CUE-101 trial. Ken will be joined by Dr. Matteo Levisetti, who recently joined Cue Biopharma as Senior Vice President of Clinical Development. Matteo brings a great deal of clinical development experience with immunotherapies, and we're pleased to have him on our team. After Ken and Matteo speak, Dr. Anish Suri will provide a progress update on our IL-2-based CUE-100 series and its derivative programs, Neo-STAT and the recently introduced novel bispecific, RDI-STAT what to we refer to as RDI-STATs programs. Designed to address cancer heterogeneity and tumor escape mechanisms. Anish will also update the recent progress in our autoimmune disease programs and pipeline, including the addition of the CUE-400 series. A new series that differentiates and expands regulatory T cells for addressing diverse autoimmune indications with unknown or polycharacterized autoantigens. Kerri Millar will then summarize our financial status, after which I'll return for closing remarks. First, I'll begin with a brief overview of the progress we've made towards the achievement of our stated corporate objectives. As an overarching theme, as depicted on the next slide, #4, we aim to restore immune balance by modulating the activity of disease-relevant T cells directly in the patient's body. This is the central pillar upon which our entire pipeline of immune modulating programs is based. We believe our proprietary Immuno-STAT will allow us to harness the fullest potential of an individual's intrinsic immune cell repertoire for restoring immune balance and thereby health while avoiding the deleterious side effects of broad immune stimulation or suppression. In addition to the selective modulation of T cell activity, we believe Immuno-STATs offer several key points of differentiation over competing approaches, including modularity and versatility to provide broad disease coverage, standard manufacturability and convenient administration. An important foundational aspect of our development strategy is to utilize the ongoing clinical trial of CUE-101, not only to define a potential clinical registration path for the drug candidate per se, but also to generate a representative safety and efficacy data set potentially applicable in principle to the entire CUE-100 series. As the underlying framework for the IL-2-based CUE-100 series remains essentially the same across programs, with the primary difference being a 9 to 10 amino acid antigenic epitope in the MHC or HLA binding group. Then by implication, the clinical results for CUE-101 may provide mechanistic support for the entire series. To this point, we now turn to the next slide, Slide #5. As depicted, we have exploited the IL-2-based CUE-100 series to further design and develop additional drug candidates with variations of the epitope on the Immuno-STAT framework, such as WT1, which is Wilms' Tumor 1, designated as CUE-102, our KRAS G12V, to expand patient reach and potentially address resistance mechanisms, we've also derivatized the CUE-100 series, providing us with Neo-STATs to address tumor heterogeneity and redirected Immuno-STATs or RDI-STATs, to address resistance mechanisms of HLA loss or tumor immunogenicity. In addition and not shown on this slide, we've also utilized the framework's modularity to engineer Immuno-STATs for antigen-specific inhibition of autoreactive CD4 T cells via PD-L1 for treating autoimmune diseases, and this is the CUE-300 series with known autoantigens, such as the immunogenic proinsulin epitope for the treatment of type 1 diabetes. And this is currently being developed in our collaboration with Merck. We've also deployed the engineered IL-2 variant from the CUE-100 series to design a first-in-class bispecific molecule possessing both IL-2 and a TGF-beta portion. This is referred to as the CUE-400 series for pathway specific modulation, for stimulating-induced Tregs or iTregs to address chronic autoimmune diseases where the autoantigens are unknown or not well characterized. Anish will elaborate upon these various developments during his section of program review. Through our focused efforts throughout 2020, we believe we are well positioned to demonstrate the value proposition of Immuno-STATs as potential breakthrough immunotherapies in the coming months and throughout 2021. With that, I'd now like to turn the call over to Ken to provide a summary of our clinical observations with CUE-101. Ken?

Thanks, Dan, and good afternoon, everyone. As always, I'd like to say thank you to all of the participating principal investigators. Their names are shown on the next slide, Slide 6. Throughout the COVID-19 pandemic, we have continued to screen and enroll HPV 16 positive head and neck cancer patients to participate in our trial. We have fully enrolled cohort 7 and are currently expanding up to 9 patients in each of cohorts 5 and 6 as we focus in on the selection of our expansion cohort dose. The next slide, Slide 7, shows a high-level summary of the clinical design and dosing cohorts for our ongoing Phase I trial of CUE-101, enrolling second line and beyond patients that are HLA-0201 positive with recurrent or metastatic head and neck squamous cell carcinoma, driven by HPV 16. To date, 33 patients have been enrolled with 31 of 33, having previously failed both platinum-based chemotherapy and checkpoint blockade and therefore, entering the trial receiving CUE-101 as third, fourth or beyond lines of treatment for their metastatic disease. As I've noted in previous earnings calls, the second part of the trial protocol provides the opportunity to dose up to 9 patients in any given cohort where we see evidence of clinical activity or PD effect in order to enhance our ability to choose an appropriate dose for the Part B expansion in the presumed recommended Phase II dose if we had no evidence of dose-limiting toxicity while simultaneously seeing evidence of dose-dependent PK plus evidence of agent specific PD plus evidence of clinical effect. And this is exactly what we have observed to date. Since the last earnings call, we completed enrollment of Cohort 7 at 8 milligrams per kilogram of CUE-101 without reaching a maximally tolerated dose or MTD. We are now expanding Cohorts 5 and 6 with the expectation that we will choose the expansion dose in the next quarter. Several observations give us confidence that our data is maturing to allow us to make an informed decision to choose our expansion dose. First, 33 patients in Cohorts 1 through 7 have received over 100 infusions of CUE-101, 3 weeks apart without reaching an MTD. Even though we are still in the dose escalation phase of the trial, we've already had 5 heavily pretreated patients demonstrating confirmed stable disease after receiving CUE-101. All of these patients who received CUE-101 as third, fourth or fifth line therapy. We also continue to monitor progression-free survival and overall survival closely and continue to observe what appears to be an enhancement of survival of patients in the CUE-101 dose escalation trial. While still early and part of the dose escalation study, the overall survival of these patients is encouraging and continues to be monitored closely. Because as a reminder, overall survival is the primary endpoint for FDA approval in oncology. Second, as reported in the previous earnings call, our pharmakinetics data reveals dose-dependent exposure without any evidence or effect of antidrug antibodies on PK and exposure in patients that have received multiple doses of CUE-101. And third, the sustained increase in exposure with increasing doses of CUE-101 has led to observed pharmacodynamic effects, including early evidence of proliferation of tumor-specific CD8 T cells versus the broader CD8-positive T cell compartment and an increase in natural killer cells or NK cells. We have previously shared early data on the increase of E7 specific CD8-positive T cells and patient blood samples at various time points dosing of -- after dosing with CUE-101. The next slide, Slide 8 shows additional PD data that point to a dose-dependent notable increase of NK cells in circulation 8 and 15 days post the first dose of CUE-101. The increase of NK cells is evidenced starting at around Cohort 3 and becomes more pronounced in the higher dose cohorts, especially Cohorts 5 and 6. In addition, we also see a transient increase in CD4 positive T cells, presumably Tregs. However, in contrast to NK cells that continue to demonstrate an increase at day 15, the Treg population returns back to baseline levels. We believe the notable increase in NK cells and the transient effects on Tregs are both likely in response to the IL-2 component of CUE-101. Let me now show you a representative example of a patient that summarizes these observations. The next slide, Slide 9, shows a patient that had failed local therapy and then failed therapies with chemotherapy plus cetuximab as well as pembrolizumab for recurrent disease. Notably, the patient had progressive disease within 9.4 weeks on the prior regimen of pembro. The patient was then treated with CUE-101 as third line therapy for their metastatic disease and remained on study with stable disease for over 18 weeks. The next slide, Slide 10, shows the PK exposure for the -- data for this patient, which was dose proportional across all cohorts as well as the observed increase in E7-specific T cells in their cycle 5, day 1 blood sample. Slide 10 also shows that the patient had stable disease for 18 weeks or nearly doubled their time on a checkpoint inhibitor. Furthermore, it is important to note that this patient did not have progressive disease and came off study for off-protocol reasons. Anecdotally, as shown on the next slide, Slide 11, the characteristic of additional recent data is a biopsy of the lesion from this patient taken shortly after the end of treatment when the patient was off protocol. This biopsy revealed evidence of antitumor activity, including necrosis and T cell infiltration, as well as evidence of PD-L1 expression on the tumor cells, as you can see on the slide. Of note, this is a cohort 4 patient treated at 1 milligram per kilogram CUE-101, which is the starting dose for the combination study with pembrolizumab in the first-line recurrent or metastatic head and neck cancer study. The next slide, Slide 12, shows another representative example of a patient that we believe demonstrates an effect of CUE-101 on tumor lesions and tumor lesion size. This Cohort 5 patient had most recently failed nivolumab, another checkpoint inhibitor after 28 weeks on therapy. The patient required COVID-19 in came off study while still with stable disease after 28 weeks of therapy with CUE-101. The next slide, Slide 13, shows that this patient had 3 target lesions we were monitoring radiographically. On the first scan after 7.5 weeks and after receiving 2 cycles of CUE-101, there were variable observations with 1 lesion remaining unchanged from baseline, 1 lesion growing modestly by about 8% and a third lesion growing to 18%, just under the 20% allowed prior to designation of progressive disease. It's important to note regarding this patient that went with the next scan 6 weeks later, it was observed that the lesion, which had shown the largest degree of growth on that first scan, had a significant reduction on the second scan and was back to baseline on the third. Our data showing initial tumor growth and then reduction is similar to observations by others in the evolving I/O field, supporting the premise that it may take more time to see responses with immunotherapy, such as CUE-101 as compared to classic cytotoxic therapies. So the totality of our findings to date, including the representative data just presented, has led us to draft a clinical trial protocol amendment that will allow patients to remain on study at investigator discretion if they demonstrate radiographic progression, but are clinically stable. This will provide the physician investigators the opportunity to give patients who may be responding clinically that is feeling better, but whose scans do not yet show radiographic response, the further opportunity to assess potential benefit from CUE-101. We are also amending the protocol to add measuring response by iRECIST criteria to the exploratory endpoints, reflecting the evolving nature of activity and responses in the I/O field overall. Furthermore, as CUE-101 is an activator of the immune system, its clinical beneficial effects may still be observed in patients even after they have ended their participation in our clinical trial. As such, we are also amending the protocol to allow collection of data regarding follow-on anticancer treatments that patients may receive to gain further insights into our survival observations. The next slide, Slide 14, shows our collaboration with Merck for KEYNOTE-A78, our frontline therapy Phase I trial to evaluate CUE-101 in combination with pembrolizumab or KEYTRUDA for patients with HPV-positive head and neck cancer, who are also HLA-0201 positive. The first patient at the cohort 4 CUE-101 dose of 1 mg per kg and KEYTRUDA dose of 200 milligrams per kilogram every 3 weeks has been successfully dosed on this trial and several more patients have been and are being actively screened for enrollment. The next slide, Slide 15, reviews and reminds us of our preclinical published results showing that the combination of CUE-101 and an anti-PD-1 antibody resulted in significant antitumor activity, as noted by the purple line on the left as compared to either agent alone. This activity was accompanied by significant increases in E7-positive T cells in the blood as well as the tumors of mice shown in the right panels. Our enthusiasm for our findings to date have bolstered our confidence in the promise of CUE-101 as a monotherapy as well as in combination with pembro. The recent recruitment of Dr. Matteo Levisetti as Senior Vice President of Clinical Development, underscores our confidence of the recent progress in our ongoing clinical trial. Dr. Levisetti brings a wealth of experience in the development of I/O agents from Phase I to registrational Phase III clinical trials. Over the next quarter, Matteo plans to expand the clinical operations team to support the Phase Ib expansion, the combination Phase Ia/Ib trial and the neoadjuvant studies we have described in previous earnings calls. I am personally excited about our progress and pleased to welcome Matteo on board as our partner in developing CUE-101 as well as in shepherding our next agent, CUE-102 through the IND process. I will now hand over the call to Matteo to say a few things.

Thanks, Ken. I'm delighted to join the Cue team at this exciting juncture of the company's continued corporate evolution. My own background and training in clinical medicine and immunology, coupled with immunotherapy drug development experience at Merck, Roche, Pfizer and several biotech companies have provided me I believe with a solid foundation and breadth of experience that I'm excited to deploy to lead Cue's clinical development pipeline and to help map the future vision and strategy. From a personal immunological perspective, I think the science that you and Dan outlined exemplify the potential for broad utility and application of the core technology platform, both in immuno-oncology and autoimmune diseases. I think the data emerging with clinical observations of the IL-2-based CUE-100 series via CUE-101 has the potential to open up many untapped opportunities in immuno-oncology. In addition, the progress in autoimmunity, both with the antigen-specific approaches, but also with the more recent development of pathway specific therapeutic strategies to induce and expand regulatory T cells, are exciting possibilities for patients suffering from chronic autoimmune and inflammatory diseases. These opportunities of selectively modulating the immune repertoire, be it in immuno-oncology or autoimmune disease, are really exciting from a physician's perspective. And that's what essentially brings me here. I am delighted to be with this team and with this company. I will now hand the call over to Anish to discuss other advances in our pipeline and platform.

Thanks, Matteo. Thanks, Ken. And I'd like to emphasize the key observations that Ken presented in the previous section, that have a significant impact on the evolution of the broader pipeline of assets in immuno-oncology. Most importantly, the safety, tolerability and the observed clinical activity of CUE-101 gives us bolstered confidence with the continued build-out of the IL-2-based CUE-100 series. As shown on Slide 16, the core framework, as you appreciate of the 100 series is conserved with respect to the IL-2 composition. The primary difference really swapping of the T cell epitope to change the target indication. To this end, we've continued to make very good progress with the Immuno-STAT pipeline assets that target antigens like Wilms' Tumor 1, WT1 and the mutated KRAS G12 to valine peptide that has been well-characterized by prior studies. We've recently presented these data, including most recently at the IO360 meeting last month. CUE-102, which is our next clinical candidate, targeting Wilms' Tumor 1 is slated for an IND filing in the first half of 2022. All IND-enabling activities are currently in progress and on track to meet this time line. I'd like to now focus on Slide 17. As shown here to address tumor heterogeneity, we've been developing the Neo-STAT platform to target multiple antigens or even personalized neoantigens. And to remind you, the Neo-STAT platform allows us to generate the core generic scaffold of the IL-2-based 100 series without a tumor peptide. In other words, this is an empty stabilized HLA molecule to which a desirable tumor epitope can be efficiently conjugated. This is in contrast to the classical Immuno-STATs where in each tumor epitope is a part of the fusion protein. Hence, each therapeutic molecule requires a separate cell line for generation of the clinical-grade material. So from a functional biology perspective, the Neo-STAT and Immuno-StAT molecules are very comparable as shown in the graphs on the right, with examples of T cell expansions from human blood involving 2 different antigens, CMV and MART-1. In either case, the degree of T cell expansion was very similar between the Immuno-StAT or the Neo-STAT. From a clinical application perspective, the current clinical data sets with 101 provides strong support for Neo-STATs, since again, the core IL-2 and HLA scaffold remain the same. The next slide, Slide 18, highlights an equally important derivative of the Immuno-STAT platform, which is aimed at addressing tumor escape mechanisms involving loss of tumor antigen processing and presentation components, including the loss of HLA molecules. A notable fraction of human cancers, upwards of 30%, in some cases, will undergo loss of HLA molecules, which makes them essentially invisible to tumor-specific T cells. This escape mechanism presents a significant challenge for therapeutic approaches focused on enhancing anti-tumor T cell immunity. These include checkpoint inhibitors, TCRT cell therapy approaches, tumor vaccines or even classical Immuno-STATs. Our approach to addressing this escape mechanism takes advantage of related observations from cellular analysis of human cancer tissues, revealing the significant presence of CD8 T cells that are specific for viral antigens. Such as EBV flu or CMV. In other words, a fraction of the protective memory antiviral T cell repertoire localizes to the tumor tissue likely in response to chemotactic signals that are agnostic of the specificity of the T cells. A couple of the seminal papers highlighting these findings are actually noted on the slide. These observations actually present an attractive opportunity for us to leverage the 100 series to generate a novel class of bispecific therapeutic molecules as shown in this slide, to redirect or trick the viral T cell repertoire to kill the cancer cells, including those that have lost the expression of HLA molecules. We call these new class of bispecific molecules, redirected Immuno-STATs or RDI-STATs. The RDI-STATs are essentially virus specific Immuno-STATs but contain a tumor targeting arm that allows for binding to a tumor cell surface antigen, such as a Trop2 or HER2 mesothelin, et cetera. Thus, in this manner, the tumor cell coated with a RDI-STAT molecule appears like a virally infected cancer cell, which can then be recognized and killed by the antiviral T cells that populate the host and the tumor tissue. We believe this approach has several unique advantages. It circumvents the tumors lack of HLA or antigen presentation. It harnesses a pre-existing robust antiviral T cell repertoire within the host. It's an opportunity to alter the tumor microenvironment via localizing an active immune response. From a safety perspective, this approach is very distinct from other bispecific molecules that indiscriminately activate every T cell and also result in systemic cytokine release and toxicities. And most importantly, it leverages the clinical observations provided by CUE-101, especially as it relates to the IL-2 molecules. I'd like to now move to Slide 19 to provide you an update on the autoimmune front. Our core strategy here has centered on 2 key approaches, antigen-specific and pathway-specific. The antigen-specific approach deploys Immuno-STATs to modulate autoreactive T cells and diseases with well-characterized antigens such as type 1 diabetes. In contrast, the pathway-specific approach is focused on induction and expansion of regulatory T cells for broad applications in numerous autoimmune diseases with diverse antigens or unknown antigens. As reported previously, we've been collaborating with Merck on the antigen-specific approach focused on 2 autoimmune diseases, 1 of which is type 1 diabetes, and the other is undisclosed. We've made significant progress in this collaboration, which underscore the extension of our relationship with Merck late last year to focus on optimizing potential lead clinical candidate molecules. We recently presented a progress update on these efforts via a talk at the antigen-specific tolerance meeting in January of this year. Those data slides, by the way, are available on our website. So please feel free to review those. Today, however, we would like to focus on the significant progress with the pathway-specific approach, wherein we've generated a first-in-class fusion protein containing the 2 key obligatory signals of IL-2 and TGF-beta for generation of induced regulatory T cells or Tregs. We believe this molecule also referred to as CUE-401 provides an unprecedented opportunity to reset immune balance for numerous autoimmune diseases, graft-versus-host disease and even transplant rejection. The next slide, Slide 20, provides additional insights into our focus on iTregs over the natural Tregs or also known as nTregs. The nTregs construably express the high-affinity IL-2 receptor alpha subunit, hence, many current approaches have focused on generating IL-2 variants that are biased towards the IL-2 receptor alpha, also known as CD25, to enable expansion of nTregs. In contrast, and as listed on this slide, we believe that targeting the iTregs via our approach provides a much broader opportunity and also several advantages over in nTregs. Most importantly, from a disease perspective, conversion of the pathogenic rogue repertoire of autoreactive T cells towards a regulatory phenotype as iTregs is an attractive strategy for restoration of immune balance. On the right side, you can see the design of CUE-401, which contains the 2 key signals for ITreg differentiation, an IL-2 variant and a TGF-beta variant. Importantly and in contrast to other approaches focused on nTregs, the IL-2 variant is not biased towards IL-2 receptor alpha. In fact, this is the same IL-2 that is derived from the CUE-100 series for oncology, which has been dosed successfully in human subjects and has substantive data related to the IL-2 moiety from a safety and tolerability perspective. To remind you, CUE-101, our lead clinical candidate in oncology from the 100 series has the same IL-2 except in a higher valency or 4 IL-2 molecules with an each molecule of 101 and in a different framework that targets tumor-specific T cells in that context. In contrast, CUE-401 has a single molecule of IL-2 and the end terminus of the Fc, along with the TGF-beta variant present on the C terminal are shown here for induction and expansion of induced regulatory T cells. The following Slide 21 demonstrates promising early data for CUE-401, dependent induction of iTregs from CD4 positive T cells from healthy human donors and from patients suffering from inflammatory bowel diseases, IBD, and rheumatoid arthritis, RA. note that the level of Treg induction with CUE-401 is comparable to or better than what is seen with the recombinant wild-type IL-2 and TGF-beta, as shown in the open symbols here. Furthermore, as shown in the next slide, Slide 22, iTregs induced by CUE-401 demonstrate functional suppression of polyclonal effector T cells. In these studies that were conducted with several human donors, CUE-401-induced iTregs were incubated in varying ratios with the responder effector T cells, shown as the T responder here. As you can see, iTregs induced by CUE-401, depicted by the blue symbols potently inhibit activation and polyclonal T cell proliferation stimulated with anti CD3, CD28 antibodies. In contrast, little to no suppression is noted with the non-iTreg-controlled CD4 T cells shown in red. Based on what we've accomplished so far, we remain highly committed to continue to develop this program forward towards the clinic. We believe CUE-401 could have the transformational potential for addressing the unmet medical needs for many autoimmune and inflammatory diseases. Lastly, Slide 23 connects the different pipeline vignettes and opportunities that are enabled by the CUE-101 clinical experience. The encouraging metrics with CUE-101 with respect to safety and tolerability, favorable PK and exposure, emerging PD and clinical data support multiple therapeutic opportunities as shown here. First off, it's our belief that the Immuno-StAT pipeline assets, including CUE-102, which targets Wilms' Tumor 1 and the KRAS G12 valine molecules have a reduced risk profile due to the clinical observations of CUE-101. Secondly, we also believe that the Neo-STAT platform, which is a derivative of the IL-2-based 100 series and is designed to address tumor heterogeneity also directly benefits from the CUE-101 clinical data. Third, we also believe that the development of the bispecific RDI-STATs, as I just showed you, designed to address tumor escape mechanisms of HLA loss or antigen presentation defects also derive benefit from CUE-101 since the core IL-2 framework is essentially the same. And lastly, as discussed, our novel fusion protein CUE-401 that induces regulatory T cells for autoimmune and inflammatory diseases contains a single molecule of the same IL-2 variant as incorporated into CUE-101. To summarize, we believe that the depth and richness of our growing pipeline of programs is supported by the CUE-101 clinical experience, and we very much look forward to further developments as we move these various programs towards clinical testing. With that, I'll now pass the call along to Kerri to review the financial details. Kerri?

Thank you, Anish. Turning now to Slide 24, I'd like to provide a brief update on our financial results for the 3 months and year ended December 31, 2020. The company reported collaboration revenue of approximately $0.5 million and $1 million for the 3 months ended December 31, 2020 and 2019, respectively. The decrease was primarily due to adjustments in the LG Chem and Merck collaboration budgets and full-time employee allocations. In the case of Merck, the adjustments were made to reflect the additional financial report that we will receive to further develop the preclinical drug product candidates under our research collaboration. Research and development expenses were $8 million and $7 million for the 3 months ended December 31, 2020 and 2019, respectively. This increase was due to the clinical trial activity for the CUE-101 monotherapy and combination clinical trials hiring of research and development personnel in the first quarter of 2020, manufacturing costs for CUE-102 clinical material as well as development on the Neo-STAT cell line. General and administrative expenses were $3.4 million and $3.1 million for the 3 months ended December 31, 2020 and 2019, respectively. The increase was due primarily to stock-based compensation and legal fees incurred during the fourth quarter of 2020. We recorded collaboration revenue of approximately $3.2 million from our collaboration with Merck and LG Chem for the year ended December 31, 2020, a decrease of approximately $300,000 from the same period in 2019. This decrease was primarily due to adjustments in the LG Chem and Merck collaboration budget. Research and development expenses were $33.5 million for the year ended December 31, 2020, as compared to $27.5 million for the same period in 2019. This increase in R&D expenses were due primarily to an increase in the clinical trial activity for the monotherapy and combination trials of CUE-101, hiring of research and development personnel throughout the year to support our growing pipeline and drug manufacturing costs for CUE-101 and CUE-102 clinical trial material as well as the development of the Neo-STAT cell line. General and administrative expenses were $14.7 million for the year ended December 31, 2020, as compared to $12.7 million for the same period in 2019. This increase in G&A expenses was primarily due to increases in stock-based compensation expense and legal fees, which were partially offset by a decrease in travel expense as the COVID-19 pandemic continue to hamper our business travel throughout 2020. We finished the year with approximately $84.9 million in cash, cash equivalents and marketable securities and working capital of approximately $71.2 million. During the year ended December 31, 2020, we extended our cash runway with $56.7 million from the sale of our [indiscernible] of common stock under our at the market equity offering through Stifel Nicolaus & Company who acted as sales agent. We believe our cash, cash equivalents and marketable securities as of December 31, 2020, will allow us to support the development of our Immuno-STAT platform, including the clinical development of CUE-101 into the third quarter of 2022. I'll now turn the call back over to Dan for closing remarks. Dan?

Thanks, Kerri. As outlined on this call, our primary objective is to develop novel drugs based on the Immuno-STAT platform to provide meaningful therapeutic benefit for patients suffering from debilitating diseases by restoring immune balance. The next slide, Slide 25, depicts our growing pipeline of candidates through which we believe we are well positioned for creating substantial value and growth potential for our shareholders throughout 2021 and beyond. By continued execution of our corporate strategy, we aim to demonstrate our competitive advantages and market positioning of the Immuno-STAT platform and associated programs. Specifically, we believe the CUE-101 monotherapy trial provides a potential registration path forward as a single agent therapeutic and the combination trial with KEYTRUDA provides the prospects to enhance patient reach and market size by moving upstream to first line patients, where we anticipate the potential for significant mechanistic synergies as demonstrated in our preclinical studies. We're continuing to develop a robust and growing pipeline of additional targets from the CUE-100 series and its derivative programs, Neo-STAT, in the bispecific RDI-STAT as well as progressing our Q3 hundred series under our Merck partnership and defined indications where the autoantigens are well-known and characterized. Furthermore, as described by Anish, we have also recently developed a bispecific drug candidate, CUE-401, indicated for autoimmune diseases with unknown or multiple autoantigens. We believe that through the ongoing development of CUE-101 and our other CUE-100 series Immuno-STATs and our CUE-300 and now 400 series, we have the potential to be positioned as a pioneering breakthrough biopharmaceutical company that can transform immunotherapy through targeted immuno modulation of disease-relevant immune cells directly in the patient's body. All right. Now moving on now to our expectations for milestones and achievements during 2021 as shown on the next Slide 26. We anticipate continuing observations pertaining to CUE-101's clinical activity and expect to select the monotherapy patient expansion dose in the monotherapy trial, continued dose escalation in our combination trial and commencing the neoadjuvant trial by the second half of this year. Additionally, we anticipate filing of an IND for our second drug candidate, CUE-102, in the first half of 2022. We're also planning to initiate and expand CMC activities for cell line production of Neo-STAT and KRAS G12v, respectively, in the second half of the year in preparation for IND-enabling studies. Also, we plan to achieve optimization towards completing proof of mechanism for CUE-301 by year-end, which would enable Merck to determine to proceed with further development for indications where the autoantigen is known and well characterized, such as type 1 diabetes. Furthermore, we plan to establish foundational preclinical data for CUE-401 for addressing autoimmune indications. Finally, we'd like to thank our dedicated employees whose commitment and professionalism throughout the challenges of the past year have allowed us to remain focused on execution of our ongoing corporate development. We would also like to thank our Board of Directors for their support and guidance. I want to thank our shareholders who provide us with the essential resources to continue our important work, developing promising therapeutic candidates for patients in need. And most importantly, we want to thank the patients and their families involved in the clinical trials, allowing our clinical investigators to study and assess the potential therapeutic benefit of our promising drug candidates. Thank you very much for your attention on today's call and your ongoing interest. And I'd like to now turn the call back over to the operator for questions.

[Operator Instructions]. Our first question is from Stephen Willey with Stifel.

So I wonder if you can maybe speak a little bit to the kinetics of response that you're now characterizing. I understand that you kind of get this delayed response, which is, I guess, somewhat characteristic of immunotherapy. But how does that interplay with some of the kinetics that you're seeing with respect to increases in antigen-specific T cells. I think in that 1 patient that -- in the 1 mg per kg cohort, you had highlighted that they had seen a sevenfold increase in E7-specific T cells, I think, at cycle 5, day 1. Are you seeing, I guess, kind of a graduated increase in those E7-specific T cells that kind of mimic what you're seeing in terms of lesion responses? And then how do you think the interplay of this transient increase in key Tregs is contributing to these response kinetics as well?

Okay. I have Anish answer the first part of that, and then Ken can elaborate further as the clinical implications.

Yes. Steve, this is Anish. So good question around T cells. We have noticed T cells, as you pointed out, in several subjects, including the patient with obviously the biopsy sampling. One of the things, Steve, that is difficult to assess simply because of timing, is to understand the kinetics of T cells in terms of evolution and the migration. So we have our sampling for this has been every 21 days. There's obviously a lot happens between engagement when T cells are activated, that extravasate to the tissue. That's the part where we need to get a bit more insights. In other words, the blood is a good surrogate for mechanistic biomarker. But ultimately, what's happening in the tissue becomes very relevant. And then maybe a vignette of that was provided by the pathology slide that Ken shared. It's essentially also the reason, Steve, why we've focused and really prioritized the neoadjuvant study that Ken has been driving and along with Matteo now, which is to have access to the tumor tissue to be able to make those frank assessments. In our own situation with preclinical assessments, we saw an enormous disconnect between what we see in blood and then tumor tissue almost 2 orders of magnitude in some cases. Where the richness was more evident in the tumor tissue. So that's an aspect we continue to remain focused on to better understand the evolution of the response, and ultimately, where it's homing to in context of the drug design. The other thing I'd like to point out, Steve and remind everybody is of a key paper that was published by Hidde Ploegh and our founder, Steve Almo late last year, I believe, in the October, November time frame in Nature Methods. That made the point that the core scaffold of Immuno-STAT, in that case, they used the peptide part with immuno-PET imaging to make the point that, that could penetrate, extravasate and directly engage TILs in the tumor lesion. So there is the potential for CUE-101 to directly engage resident TILs, which, again, any of that activity is not quantifiable by blood. So we very much appreciate the limitations with blood. But having said that, I think the emerging aspects of seeing this is particularly encouraging. These are late-stage cancer patients, as Ken pointed out, with a compromised immune status. So we've got to take that into consideration. I think what would be interesting is to see in the first-line setting with pembro, which is a different quality of patients, whether that signature seems different. So we are eager to understand that. As for the Treg, look, these were FOXP3 positive, these are transient. This is definitely -- we -- not definitely, but it likely points to the IL-2 pharmacology that 2 come back to baseline. We have to track them out to see any evidence in sort of downstream in terms of the tumor recognition reaction. I'll tell you from a preclinical studies in -- with a murine surrogate of CUE-101 that wasn't any noticeably evident to us in those sorts of analysis. So again, we keep an eye out on these things, obviously, and try to understand. But so far, it seems to be trending with what we've sort of noticed previously.

And Ken, do you want to add-on on the clinical side?

Yes. I would just add really quickly because you covered it. One of the questions that folks have been worried about, I think, is are we delivering IL-2 to these patients because the drug has been so safe. And these PD markers, the bump in Tregs the NK cells going up, the stimulate Ki67 stimulate -- reflecting stimulation of the general CD8 population and then even more in the E7-specific T cell population, all reflect that we're delivering IL-2 in effective doses. So I think that's what I read when I see that Treg bump is IL-2 is going to stimulate cell -- T cells, all kinds of T cells. And that's what we're seeing along with the NK cells. So it actually gives us comfort that we are delivering IL-2.

Okay. That's helpful. And then just real quickly, I know the intention here is to expand out Cohorts 4, 5 and 6. I know that you have not yet reached the maximum tolerated dose. So maybe you can just kind of speak a little bit to the decision not to expand out Cohort 7.

Yes. So I think all the data that we're seeing suggests that we're seeing activity in that -- in the space of 1 mg and 2 and 4 mgs per kg. We did not hit an MTD in Cohort 7, but we did see SAEs that are suggestive to us that if we don't need to go to that high of a dose, we shouldn't -- we won't need to fill that out because I think we're going to find our active dose in the lower cohort doses, which will save on the amount of drug we need to use as well as potential toxicities down the line. We can always choose to expand later, but we are really confident that we're going to see -- we're going to find our dose somewhere between 4 and 6.

Our next question is from Ren Benjamin with JMP Securities.

Congrats on the progress. I guess just dovetailing off a couple of Steve's questions. The -- when I look at the induced changes of the NK cells and Tregs, unless I'm kind of reading it wrong, the NK cells seem to come back down a little bit by day 15. The Tregs seem to be maintaining and then coming down. It doesn't look as transient. So maybe just help me understand kind of what you guys are seeing here and whether or not it makes sense to start thinking about changing the dosing schedule as you evaluate these other cohorts because maybe something a little bit more frequent could help with the increase of the NK cells or the CD8-specific cells. And related to that, any thoughts about combining this with something like an ipilimumab or sorry, CTLA-4 inhibitor.

Yes. Ren, I'll take the NK and Tregs. So Ren, I just want to clarify in that graph that was shown the NKs are in the black symbols, the Tregs were in the red dotted lines. And for most of the patients, which we've seen and what's actually quite nice here and evident, particularly as you see cohorts 5 and 6 is a very nice expansion of NKs that through 15 sort of sustains. There's a slight -- that's maintaining at an elevated level. If you see with the TRegs in the most of the subjects, there's a transient uptick at about the day 8. But by day 15, all of them have trended down. So we -- actually, that is a positive differential between those 2 populations. And as I mentioned, what Steve asked and Ren you're asking in a sort of a related sense, the effect and outcomes of this ultimately matters at the level of the tumor reaction. So as we start obtaining more biopsies as we start to understand mechanistically at the level of even the neoadjuvant setting and hopefully even try to get -- do that in our expansion phase, I think it will be important to understand what is the representation of these populations as possible composition of the tumor infiltrates. That ultimately becomes very important for us. So that is how we are thinking about these observations, Ren. And so far as your second question for combination, I think -- as we think about the PD-1 checkpoint, that, of course, mechanistically makes very good sense to us. It's also backed by our preclinical data. And if there's data emerging from there that tells us that we should consider other checkpoints for mechanistic signatures, then we've always sort of hold those opportunities and look at them with an open mind.

Got it. Okay. And then maybe just as a second one. The Neo-STAT and the RDI-STAT platforms, I mean, all look really exciting. Especially the RDI-STAT. I guess I'd love to get a little bit more clarity as to when do you see those ultimately advancing to the clinic? Is it kind of full steam ahead for each of those programs do you think by 2022? Or is this something that ultimately gets to the clinic a couple of years from now?

No. Ren, so we've been working on RDI-STATs in the background. For quite some time. We had these, as I told you, this really came about from these fundamental observations of looking at the literature merging, which we thought was really interesting, different groups making the same observations that a significant part of the tumor infiltrate in solid cancers, ovarian, colorectal, lung, at the antiviral protective repertoire. So we've got a lot of data, which we haven't shown here, which we will be hopefully discussing in some future meetings. For example, we have data with our tool molecule, where we've made this with a -- the tumor targeting arm is an anti-CD19 and compare that to the sort of the anti-CD3 BiTE format and shown very comparable killing that's achieved at an optimal dose. And at those doses where you see optimal killing of the target cell, which express a CD19, we've not seen any nonspecific proliferation. In that case, the virus epitope, as a human CMV epitope only activation of the CME T cells. And we've not seen any production of inflammatory cytokines, whereas with the tool molecule of the BiTE, there were nonspecific activation of T cells and systemic cytokines, which is why I made the point that this could be a really important way of looking at the immune reaction. And harnessing what is a very robust repertoire that most of us have halved for decades and to repurpose that repertoire. So we are fully committed. When you say full steam ahead, that's how we are looking at this. The choice right now is really looking at a variety of solid tumor antigens to make a choice of what a first candidate may look like. But again, coming back and linking this to CUE-101, the co-framework insofar as even the HLA component in the first iteration is AO2, the epitope is a virus epitope in the IL-2 is exactly the same IL-2. So we stand to gain a fair bit from those learnings, which hopefully, as we sort of move this along the preclinical development should aid in a significant manner.

Do you think that we could see this in the client by 2022?

I'd say end of 2022 late, early 2023, Ren, I mean that would be a reasonable time frame. Of course, as you can imagine, in contrast to Neo-STAT where we've initiated CMC activities, is the cell line development for these constructs that takes most of the time for the clinical gate material.

Our next question is from Mark Breidenbach with Oppenheimer & Co.

This is Kalpit on for Mark. Maybe a couple quick ones for Anish. In the ongoing study for CUE-101, are you seeing any direct evidence of HLA on regulation in the enrolled patients for which you may see RDI-STAT as a better fit as an Immuno-STAT for these patients? And then do you anticipate presenting any preclinical data on this RDI-STAT platform at an upcoming medical conference this year?

Yes. Kalpit, very good for the first point. We've actually not probed ourselves in these late-stage patients. What we do know is actually a very nice report that was published, I believe, from Foundation Medicine a few months back that characterized loss of HLA across and in the head and neck cancer, it's 30% or high, I believe, if I'm not mistaken. So we know that there's a significant loss in particularly these late-stage patients, which actually -- when you're doing a 3x3, if you just take that statistic, 1 out of 3 patients may not have the substrate for which the immune system is dependent upon. So we've not yet fully characterizing our own because you need, obviously, biopsies to be able to quantitate HLA expression and understand if it's an allelic law sort of its component loss. We also know in the accompanying separate situation in the same disease, but in the cell therapy report published by Kite, for example, they have noticed in broad HPV-driven cancer, not just head and neck, that they see again about 1/3 of patients that have lost either the HLA or components with antigen processing and presentation, again, bringing into focus that this is a very important tumor escape mechanism that a lot of us regardless of the platform or the approach may be susceptible to ultimately. Insofar as the preclinical data, we certainly are building out those packages, and I would imagine, in the second half of this year, we'll start releasing some of that data.

Okay. And then a follow-up, I guess, I'm curious if it makes sense to use a PD-L1 version of your RDI-STAT that could be applied universally across different tumor types?

It's a very good idea. And trust me, this is something the team internally continues, and we've thought of this as well as even other modalities help within the tumor microenvironment, if you think about sopping up immunosuppressive soluble modulators and cytokines. And one of the strengths we have is the modularity of the platform allows us to do that, which is to bring in a different module to be able to look at poly specificity or polypharmacology, if you want to call it that. So we certainly thought about it Kalpit. It's, an excellent idea. It's something we continue to internally vet and keep on the forefront.

Your next question is from Ted Tenthoff with Piper Sandler.

Great. And I can tell you, you've been very busy with all of the work on the pipeline, really exciting. Also understand and appreciate the time you spent laying out the differences with respect to analyzing patients. So looking forward to more data on that. A lot of my questions were asked. I guess the 1 that I primarily have is with this 401 series, really, really cool concept here. Because this is outside of oncology, is this ultimately a program or an effort that you would envision partnering? Or is this an indication that you may ultimately be moving beyond oncology with its own efforts.

Yes. Thanks, Ted. Obviously, an important strategic decision for the company and it's one that we've been evaluating in coordination with our Board of Directors because it has significant implications in terms of the trajectory of the company. We're principally focused on oncology presently in terms of our core competencies and capacity, albeit it's an immunotherapy-centric organization focused on protein engineering. The 1 thing we don't envisage is that we're going to be partnering assets early on just to partner them to divest. So we intend to build a data set, one, from our observations in oncology, where the IL-2 moiety has already been in the clinic. I think that bodes well for at least derisking the IL-2 side of the calculus. We didn't see immunogenicity on the 100 framework. So what we want to do is make sure that we're building as much supportive data to enhance the value proposition and then look at, let's say, collaboration, partnering alliance strategies that maximize the value potential for shareholders, i.e., we're creating enough of an impact with the data set that we can retain upside potential and possibly even some co-development in the early clinical going.

Yes. And not like you need to make any decisions on that now. But really highlights the modularity of the platform. So great update.

Our next question is from Brian Skorney with Baird.

Looking at the patient in Cohort 4 with the necrosis 1 biopsy, and kind of extrapolating that a little bit to the patient Cohort 5, which seems to have tumor increase followed by regression. I mean for this patient in Cohort 5, do you guys think this is pseudoprogression that's occurring in the second patient? And have you looked at any markers, specific to the tumor at all that might be indicative of that? I know circulating tumor DNA is sort of correlated with pseudoprogression. And I think some data showing that you can delineate sort of progression on with the radiotracer uptake. Just wondering if you've looked into that at all or any of the other patients and if they share sort of characteristics of pseudoprogression?

Sure. Appreciate the question, Brian. Ken, do you want to take that?

Yes. So it's a super question. And as you probably know, except for melanoma, many immuno-oncologists consider pseudoprogression, "a dirty word". And it's really hard to characterize it. What we do see and what you're seeing in multiple clinical trials around the world as well as in everybody's clinics is that you do see these -- that it takes a while for these lesions to shrink and that as you follow these patients, you do see some increases in tumor size. And whether you call that pseudoprogression or whether you call that tumor inflammation, I think the patient, certainly, that we had the biopsy on that had a lesion that was a bit larger, but also showed this idea of necrosis as well as sarcoid-like reaction showing inflammation, lots of T cells suggests pseudoprogression. So we don't -- we, like the rest of the I/O field are evolving our thoughts about how to follow these people and that's one of the reasons why we're adding the RECIST criteria to our exploratory end points. The field is, in general, is not ready to replace RECIST with iRECIST is still the gold standard, but more and more investigators are using iRECIST to help guide their thinking. We don't have -- to be blunt, we don't have PET scan data on these patients. And we've -- we are collecting -- circulating tumor DNA, but we're still going to be evaluating that as the trial progresses. So it's too early, but it certainly has that flavor of -- and we're seeing these in large lesions because of some inflammation. So I think I answered your question. I'm really happy to expound if you need more.

And our final question is from Zhiqiang Shu with Berenberg.

A few ones on CUE-101. So for CUE-101, I think this is your first time showing the NK cell expansion data, very encouraging. I guess how do you think -- how do you put this data with the T cell expansion data, specifically only E7-specific T cells are get expanded. I guess that -- I guess, what type of cells, do you think really do heavy lifting antitumor activity there?

Yes. Look, those are the two very related but too very distinct because the NK effects of IL-2 are a lineage effect, as you can imagine. So you see this movement across patients, which is great. And as Ken mentioned, it's one of the most clear metrics of an active IL-2 compound. So we are actually delighted to see that. It's also good to have a component of polyactivity with different cell types that hold antitumor potential. On the T cell side, we have noticed this in the periphery. We've reported examples in early evidence of E7 expansions, of course, that's a rarer frequency, particularly as you're talking about even late-stage patients. But even in healthies, as you well know, the antigen-specific repertoire to characterize on a dominant specificity is it's not at the same degree as when you have a lineage specific effect. Ultimately, at the level of the tumor reaction, I think if you look at mechanistically, they both have an opportunity, and they both could be active. We from some of the biopsy, and again, this is early days that Ken presented, you could clearly see the CD8s that were juxtaposed next to cancer cells that expressing -- that were also expressing PD ligand, which furthermore sort of also validates and supports the mechanistic combination with PD-1, but this has to be -- obviously looked at now in a more deeper sense as we continue to hopefully access tissues. And again, keep on coming back to the neoadjuvant not to belabor the point, but that provides us with clear access in terms of making those comparisons. And ultimately, as this all sort of ties together and patients derive benefit, hopefully, even at the level of survival benefit, these things become apparent in the longer term as these follow-ups happen. So we think, again, not to exclude, we've kept our eyes very mind open, but it's good to see in fact that we started to notice at the level of tumor-specific T cells. It's good to see this now with NK cells. We know by preclinical data that we presented and say with the WT1 compound, and this is with all ex vivo human T cells, that are expanded with CUE-102, for example, which is a derivative of the same framework and same was notice with 101, that these T cells are polyfunctional. They produce pro-inflammatory cytokines. They are positive and they kill target cells. So I think we'll have a lot here. We'll learn a lot as we sort of continue to gather these data, but the early metrics are certainly supportive to see these impacts. And what we believe are obviously very relevant populations for an anti-tumor T cell response or an antitumor immune response, rather.

Got it. And then for the first-line combination treatment, I think that holds probably the most interesting potential there. How do you think about going into a registration trial? And what kind of data are you looking at in this initial data to read out in the second half?

Sure. Let me -- Ken, let me just take that generically, then I'll turn it over to you.

Sure.

It's an important question. And look, we made a very deliberate decision to go into this with second-line and beyond as a single agent to clearly demonstrate sort of the mechanistic underpinnings of 101 and the 100 series. So we're actually really impressed and pleased with the data we're generating to date, both from the standpoint of the tolerability, but the fact that we're seeing T cell increases, NK cell increases. We're seeing antitumor effect as evidenced on scans. We're seeing some tumor shrinkage, tumor stabilization. But most importantly, that's translating qualitatively into data as we look downstream, where we're seeing evidence of tumor necrosis. Ultimately, what matters is the survival of those patients. So we still are very confident and bullish on the prospects of monotherapy where these patients, let's not forget, these are very compromised and poor state patients who don't have a standard of care. So we're still optimistic and positive about the monotherapy prospects for a registration path. And then the combination, the rationale there is mechanistically, we're expecting to see some synergistic effects because of the fact that pembro or other checkpoint blockade approaches, in essence, require an endogenous population of activated T cells to have therapeutic effect. And that's what our platform is, in essence, driving to achieve, which is increasing that endogenous T cell repertoire. So we think it bodes well for both the monotherapy and the combination. Ken, I'll turn it to you to elaborate.

Yes. I would just say, when you think about the combination and you think about pembro being approved in that first-line setting, you're talking about response rates around 18% overall as well as a survival benefit of a couple of months compared to chemotherapy. So we recognize that if you look at our data from the mouse models that the combination of CUE-101 plus an anti-PD-L1 antibody was much better. There was more -- clearly synergistic activity. So we believe that there -- the combination study will lead to a registration path because we believe we will -- the 2 drugs together will have a much better ORR and a much better overall survival advantage than pembro alone.

Got it. And a final question on CUE-401. Since you are using the same IL-2 variant as CUE-101, I guess, how do you think about the potential dosing here? Would you use even lower dose IL-2 for this to induce iTregs? Is that the rationale that?

\ Yes. I think, look, from a biology, it's obviously very different. And it's very different than low dose IL-2 of Proleukin that has been tested in graft-versus-host disease in human subjects or in patients with autoimmune diseases, including IBD and vasculitis. These papers are out there. And that's different from the high-dose IL-2 that's used for conventional cancer immunotherapy. I think the fundamental difference here, Zhi, is the fact that it's just not the IL-2, but also a TGF-beta component that's delivering an active signal. So while we take, obviously, a lot of comfort and confidence from the established safety and tolerability of 101, we actually don't anticipate going to these sorts of levels. We have just started our early investigations into in vivo motor systems to better understand that relationship. And again, that pharmacology is slightly different than what has been done in the field or what is still being done in the field even with the IL-2 variants, where the biology is a singular access of IL-2 that is not the play. The play here is actually differentiating into a lineage phenotype for the CD4, taking advantage of 2 key signals, IL-2 and TGF-beta. So we've got a -- we've obviously got to understand this in a different manner than what has been conventionally done. But we know from some of the early data that is emerging, that this is a very sensitive pathway that can be triggered effectively, and that gives us confidence that we will have an enormous safety window compared to where what we've already learned with 101.

Ladies and gentlemen, at this time, I'm showing no further questions. I would like to end the question-and-answer session and turn the conference back over to management for any closing remarks.

All right. Thank you. Thanks, everyone, on today's call, and for those that will be listening on our archival recording for your ongoing interest in Cue Biopharma. And we look forward to providing updates on a continual basis as we continue to make progress during the upcoming quarters. So thank you very much, and everyone, take care of yourselves.

Thank you. This does conclude today's conference. You may disconnect your lines at this time, and thank you for your participation.