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Edited Transcript of CUE.OQ earnings conference call or presentation 19-May-20 8:30pm GMT

Q1 2020 Cue Biopharma Inc Earnings Call

Jun 29, 2020 (Thomson StreetEvents) -- Edited Transcript of Cue Biopharma Inc earnings conference call or presentation Tuesday, May 19, 2020 at 8:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Anish Suri

Cue Biopharma, Inc. - President & Chief Scientific Officer

* Daniel R. Passeri

Cue Biopharma, Inc. - CEO & Director

* Kenneth J. Pienta

Cue Biopharma, Inc. - Acting Chief Medical Officer

* Kerri-Ann Millar

Cue Biopharma, Inc. - VP of Finance and Principal Accounting & Finance Officer

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Conference Call Participants

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* Boris Peaker

Cowen and Company, LLC, Research Division - MD & Senior Research Analyst

* Madhu Sudhan Kumar

Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst

* Mark Alan Breidenbach

Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst

* Reni John Benjamin

JMP Securities LLC, Research Division - MD & Equity Research Analyst

* Stephen Douglas Willey

Stifel, Nicolaus & Company, Incorporated, Research Division - Director

* Thomas Eugene Shrader

BTIG, LLC, Research Division - MD & Healthcare Analyst

* Ashley R. Robinson

LifeSci Advisors, LLC - MD

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Presentation

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Operator [1]

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Greetings and welcome to Cue Biopharma First Quarter 2020 Earnings Call. (Operator Instructions) As a reminder, this conference is being recorded.

It is now my pleasure to introduce your host Ashley Robinson, Investor Relations. Thank you. You may now begin.

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Ashley R. Robinson, LifeSci Advisors, LLC - MD [2]

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Thank you, Doug, and good afternoon, everyone. This is Ashley from LifeSci Advisors, and thank you 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, Vice President of Finance and Principal Financial and Accounting 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 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 12, 2020, and quarterly report on Form 10-Q filed with the SEC on May 7, 2020, 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, May '19, 2020, 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. I would like -- I would now like to turn the call over to Cue Biopharma's CEO, Dan Passeri. Dan?

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Daniel R. Passeri, Cue Biopharma, Inc. - CEO & Director [3]

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Yes. Thanks, Ashley, and good afternoon, everyone, and thank you for joining us today for a review of our ongoing progress and first quarter financial results, which are available in more detail in our Form 10-Q, which was filed with the SEC on May 7.

As a reminder, the slides we're presenting today as well as a recording of our call will be available on our website for the next 90 days. Also as a reminder, for those of you listening in, you can advance the slides from your computer, and we'll notify you what slide we're addressing at that time. We will also be available via the e-mail provided on our website for questions that may not be addressed during today's call and you may want to ask subsequently.

Beginning with Slide 3, which shows our agenda for today's call, I'll provide a brief overview and update of our pipeline with an emphasis on our lead program, CUE-101, and that will be followed by Dr. Ken Pienta, our acting Chief Medical Officer, who will provide further details on our most recent observations from our ongoing Phase I CUE-101 monotherapy dose escalation and expansion study. Following Dr. Pienta's update, Dr. Anish Suri, our President and Chief Scientific Officer, will further describe our continued innovation and additional progress that we've made in advancing our Immuno-STAT and Neo-STAT platforms. He'll underscore how our rationally engineered IL-2-based CUE-100 series is differentiated, and finally highlight the rest of our expanding pipeline that now includes CUE-102, KRAS, Neo-STAT as well as the CUE-200 and CUE-300 programs, the latter being in a collaborative partnership with Merck.

Our progress with all of these programs demonstrates focused execution towards platform validation, especially through the ongoing Phase I trial with CUE-101 and further pipeline and platform developments. Following Anish's update, Kerri-Ann Millar, Cue Biopharma's Principal Financial and Accounting Officer, will review our current financial status, and I'll then provide concluding remarks followed by a Q&A session.

To begin, I'd like to thank our dedicated employees for their focus and consummate professionalism in diligently working under these challenging and stressful conditions from the COVID-19 pandemic. Through their efforts, we have been able to keep our lead drug candidate, CUE-101, on track in our first in-human monotherapy dose escalation Phase I trial and HPV positive head and neck cancer.

Now moving on to Slide 4, which shows an overview of our core strategic objectives and progress in the first quarter. In summary, our core objectives have been to: one, validate our Immuno-STAT platform through the ongoing generation of data from our CUE-101 clinical dose escalation study; two, expand our pipeline by selecting additional epitopes with the CUE-100 series and developing other disease applications, including autoimmune diseases, that's for the CUE-300 series; and three, to accelerate and enhance our productivity through further development of our Neo-STAT platform. To date, we have dose escalated through the first 4 cohorts and continue to generate translational data and corresponding clinical data, essential in providing proof-of-concept of our IL-2-based CUE-100 series of Immuno-STATs. And as a reminder, CUE-101 represents the first of what we believe will become a broad set of biologic drug candidates from the CUE-100 series, targeting tumor-associated antigens linked to a variety of cancers.

To this point, our near-term goal is to de-risk 101 by demonstrating safety, tolerability and clinical activity which will thereby reduce the risk profile associated with the CUE-100 series per se as well as our follow-on CUE-200 and 300 series of biologics. As a reminder, we have also been developing our Neo-STAT platform to significantly enhance our productivities and provide cost efficiencies to fully exploit the potential derisking and validation of the immuno-STAT platform, which we are in the process of generating data to demonstrate that. Anish is going to elaborate upon Neo-STAT later on in the call.

Importantly, in the ongoing CUE-101 Phase I clinical dose escalation study, favorable characteristics in drug properties, including dose proportional PK, early signs of relevant PD activity and growing evidence supporting that the drug appears to be clinically active have emerged to date from our first 3 cohorts. I want to emphasize that we are conducting the dose escalation study of CUE-101 in a monotherapy trial in second line and beyond resistant metastatic HPV positive head and neck cancer patients. In this highly challenging setting, while still quite early in our clinical study of the drug, we have observed data supporting an apparent increase in the levels of HPV reactive effector T cells in the peripheral circulation in several patients. Moreover, we have observed preliminary evidence of single-agent clinical activity of CUE-101. As we continue to build data with the objective of demonstrating single-agent activity in this challenging patient population, it is our hope that we may be able to define a clinical and regulatory path forward for monotherapy providing benefit to patients who currently have no effective alternative.

Taken together, we interpret these highly encouraging, albeit early results as evidence supporting the prospects of CUE-101 single-agent activity that needs to be further confirmed in additional patients. We also recently announced the establishment of a clinical collaboration agreement with Merck for a combination study with KEYTRUDA, which is an anti-PD-1 biologic agent as a first-line therapy in patients with advanced HPV-16 positive head and neck cancer. And a planned dose escalation Phase I study to be called KEYNOTE-A78. This collaboration allows us to expand our patient coverage by moving CUE-101 upstream into the first-line therapy, where KEYTRUDA is approved as a standard of care. The rationale to combine CUE-101 with an anti-PD-1 agent is based on our robust preclinical data which demonstrated that our promising monotherapy activity with CUE-101 was further enhanced when combined with an anti-PD-1 agent. The progress we've made in the clinic to date with CUE-101 with early emerging monotherapy data gives us bolstered confidence in moving forward with our current ongoing monotherapy trial as well as the planned Phase I trial in combination with KEYTRUDA, that has the potential of expanding the application of CUE-101 into the frontline therapy setting for recurrent or metastatic HPV-16 positive head and neck cancer patients.

Additionally, we continue to make solid progress on the development of our pipeline of drug candidates, advancing through the modularity of the platform with CUE-102, targeting WT1, our Wilms' Tumor 1 and CUE-103, which is presently being reviewed with our Asia partner, LG Chem. We also have generated supportive preclinical data for our KRAS CUE-100 drug candidate, and Anish will follow Ken's 101 update with a review of the progress made in these various programs as well as an overview of the core competitive features of our platform to remind everyone and for those of you who are first listening in.

Ken will now provide further details regarding the progress of our clinical development for CUE-101, which is our first clinical drug candidate. I'll now turn the call over to Ken. Ken?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [4]

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Thanks, Dan, and good afternoon, everyone. I'd like to first remind you about the tremendous commitment we have from the participating clinical centers and associated oncologists shown here on Slide 5. 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 study. Our investigators' enthusiasm for the CUE-101 program reflected that -- in the fact that today, we have been very successful in our prescreening process to determine eligibility for the trial, recognizing that current therapies are not or rarely curative, we put into place a system whereby patients on first-line or second-line therapy for HPV head and neck cancer are prescreened by HLA type and confirmatory HPV status to determine eligibility for future CUE-101 therapy.

The demonstrated demand of patients for prescreening underscores the significant unmet medical need in this indication.

Next, on Slide 6, we show a high-level summary of the design for our ongoing Phase I trial of CUE-101. As Dan mentioned, we are very pleased with our progress of dosing patients in this trial and are highly encouraged by observations to date. As a reminder, we are enrolling post first-line 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.

This Phase I trial has defined molecular inclusion criteria to include head and neck cancer patients that are HLA-A(*)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, really a translational precision medicine approach whereby each of our Immuno-STAT drug candidate is intended for patients with a specific molecular fingerprint. This trial is designed to provide insights into safety, mechanistic activity and potential antitumor efficacy. The trial is a standard 2-part study with the first Part A designed as a typical 3 plus 3 monotherapy dose escalation trial. Patients receive CUE-101 in once every 3 weeks via IV infusion. However, we have also provided the opportunity to dose up to 9 patients in any given cohort where we see evidence of clinical activity or PD effect. This strategy allows us to further explore PK/PD effects as well as build supporting data for determining the most appropriate dose for the Part B expansion.

Based on the safety PD and efficacy data from the dose escalation part, we will secure additional patients at that dose level during the Part B expansion phase to confirm the recommended Phase II dose for -- in a total of 20 patients. Therefore, in summary, both Parts A and B of the trial will evaluate the safety and tolerability of CUE-101 with biologic activity in antitumor responses also being followed. The expansion cohort is designed to confirm the safety, biologic activity and antitumor activity at the effective dose in additional patients to provide further support and confidence as we move into the later phases with more patients.

To evaluate on target activity, we're measuring several translational biomarkers, including T cell expansion in peripheral blood and measuring cytokine production by antigen-specific T cells. For antitumor activity, we're looking for objective responses by resist criteria at 6-week intervals or after every 2 cycles of CUE-101. I'm very pleased to report that after initiating dosing of cohort 1 in late September last year, we successfully moved forward to cohort 2 in December and cohort 3 in March. And we've now enrolled 3 patients in cohort 4 during the first 2 weeks of May. Again, to reiterate on earlier comments, the fact that we continue on schedule and made such good progress despite the COVID-19 pandemic, which has shut down multiple clinical trials that are now close to accrual, we view this as an important metric of the commitment of our clinical collaborators and the enthusiasm they have for our approach to potentially provide clinical benefit to their patients in need.

As a reminder, our preclinical modeling led us to initiate dosing with cohort 1 and what we believe is a low biologically active dose. And that a biologically and clinically active dose may be achieved starting in cohorts 3 or 4.

Shown in Slide 7 are the dosing groups for our patient cohorts. We initiated the trial at 0.06 mg/kg with a threefold expansion up to cohort 3 and then a twofold increase for subsequent cohorts. As noted on this slide, we compared the absolute dose by mass as well as molar content of IL-2 to the approved dose of Proleukin, which is 0.037 mg/kg. Proleukin is the wild-type IL-2 molecule, generally known as Aldesleukin. In the second cohort on a molar basis, we were already above the approved dose of Proleukin. And by the 34th cohort, we are approximately four to eightfold in molar excess. To date, the 12 patients in cohort 1 through 4 have received a total of 31 infusions of CUE-101, 3 weeks apart with what appears to be an attractive safety profile with limited toxicity. 1 patient in cohort 4 at the 1 mg/kg dose, having infusion reaction that resolved quickly. And recall that we've shown that this dose is about eightfold higher in terms of administered IL-2 than the IL-2 delivered by an approved dose of Proleukin.

With this data, we are confident that we can deliver high doses of IL-2 on target safely. We continue to be highly encouraged by our early progress and observations, including early evidence suggesting biologic activity. We have observed preliminary signs of T cell expansion and activation in our initial PK/PD results that we plan on confirming and extending in future analyses, coupled with clinical evaluations. Importantly, we have now observed early signs of biologic and clinical activity. In cohort 1, a patient inadvertently received 5x the prescribed dose of our CUE-101 dose between the doses intended for cohort 2 and 3. This patient demonstrated early signs of T cell expansion as well as tumor regression on skin after receiving this dose, but also developed worsening of a preexisting bullous pemphigoid rash. CUE-101 was discontinued, but the patient remained with stable disease, off therapy for several months before eventually progressing. 1 patient in cohort 2 demonstrated early signs of T cell expansion and had stable disease at first scan but did not sustain a continued response. Another patient from cohort 2 has confirmed stable disease with tumor regression of the target lesion. This heavily pretreated patient who progressed well on therapy with a checkpoint inhibitor continues on study. Also, a patient in cohort 3 has demonstrated activation and expansion of T cells and remains on study. We note that we are still in the dose escalation stage of our Phase I trial and continue to monitor the 5 patients we are continuing to treat. We will provide further details as they become available over the course of the study.

Based on the totality of these metrics, we will continue to evaluate and report on the emerging data as we prepare to advance to the dose expansion Part B of the current study.

In addition to the ongoing immunotherapy trial of CUE-101 and HPV positive head and neck cancer, we show in Slide 8, our collaboration with Merck to initiate and have submitted to the FDA, a concurrent study to evaluate CUE-101 in combination with pembrolizumab or KEYTRUDA as frontline therapy for the same indication in patients who are also HLA-A(*)0201 positive, our intention is to continue moving forward with the monotherapy trial for second-line or later HBV positive refractory and metastatic head and neck cancer patients and enhance our patient reach by moving into frontline patients in combination with KEYTRUDA, which is the current standard of care.

In this trial, referred to as KEYNOTE-A78, we intend to translate our preclinical findings, demonstrating a highly significant synergistic antitumor activity with CUE-101 combined with an anti PD-L1 antibody. These data, along with the CUE-101 monotherapy activity in the preclinical tumor model were recently published in a manuscript in Clinical Cancer Research last month. We intend to commence this trial in the second half of this year, once we've confirm the safety of CUE-101 in the Phase I trial. Furthermore, Slide 8 also shows that we have the option of evaluating CUE-101 in the neoadjuvant setting in patients newly diagnosed with localized head and neck cancer. And finally, once we have established clinical proof-of-concept for CUE-101 in head next squamous cell carcinoma, we may expand opportunistically into other HPV-driven cancers, for example, cervical and anal cancers.

I will now hand the call over to Anish to discuss other advances in our pipeline and platform. Anish?

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [5]

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Thanks, Ken, and thank you to everyone listening in. I hope all of you and your families are safe and well through these times.

I'd like to remind everyone of the scientific vision that has underscored our focus and efforts from the very start, a vision that was centered on a singular all-important question, which is how does one take advantage of the selectivity and specificity of the immune response while not breaching patient safety? We believe our Immuno-STAT, as exemplified by the CUE-100 series as shown on Slide 9, of which CUE-101 is representative as a rational solution, anchored in sophisticated protein engineering.

From an elegant perspective, the best map of the landscape is the landscape itself. To that end, the landscape of T cell modulation in cancer immunotherapy can involve many elements, however, the key fundamental signals for specificity, coupled with controlled activation are what ultimately govern the outcome of the immune reaction. These very core elements are incorporated into the molecular framework of the CUE-100 series. The 2 key signals on the 100 series as shown in Slide 9, consists of stabilized peptide HLA molecules to engage the tumor-specific T cells via the T cell receptor, thereby locking in the specificity combined with rationally engineered IL-2 molecules that selectively act upon those T cells to control their activation.

We believe this controlled mechanism is an obligatory prerequisite for T cells in cancer immunity. In other words, in absence of the appropriate antitumor T cell repertoire, the application of a T cell modulating approach, be it singular cytokine therapy like IL-2 or its variants or antibodies targeting checkpoint molecules, is likely going to be suboptimal or futile endeavor.

From the earliest approval of Proleukin, IL 2 has been a validated target for T cell activation. The challenge for broad application of IL-2 has pertained to safety liabilities due to cytokine release and vascular leakage and indiscriminate activation of immune cells and broad T cell subsets, including regulatory T cells or Tregs. We evaluated the incorporation of IL-2 in the CUE-100 series guided by structure based rational protein Engineering solutions.

From the very beginning, we sought to achieve 2 key objectives: one was to generate an IL-2 that avoids the safety liabilities and Treg engagement properties of wild-type IL-2. And two, ensuring that the IL-2 was selectively delivered to tumor relevant T cells. The output of these efforts resulted in the generation of the CUE-100 series framework, as you see here in Slide 9. The top-down view of the ribbon diagram of the CUE-100 series, as shown here, provides a good contextual perspective for the spatial engagement of these molecules by tumors specific T cells. Note, there are 2 modifications to the IL-2 molecule that are important for its specificity and selectivity. The first is application of binding to IL-2 receptor alpha subunit in order to avoid Treg engagement. The second modification is the attenuated binding to the IL-2 receptor beta subunit, such that the IL-2 activity is biased to those T cells that are docked to the specific peptide HLA complex via their T cell receptors or TCRs. We believe this engineered biologic framework allows us to maintain specificity and selectivity while avoiding the systemic toxicities associated with indiscriminate IL-2 dependent activation of many different cell types. And indeed, as you've heard from Ken and as you've seen the dose cohorts, the initial clinical data sets certainly appear to support this thesis.

Several key points should be emphasized. First, we have a novel biologic scaffold that demonstrates exposure and dose proportionality in line with projections, which is highly encouraging. Furthermore, we have not seen major safety liabilities at doses where in a molar content comparison of IL-2, we are significantly higher than the approved dose of Proleukin. For example, at the dose level in the fourth cohort, CUE-101 has approximately 8x the molar content of IL-2 compared to Proleukin. In addition, the early PD data seems to suggest that we have activity in engaging and expanding the targeted T cells based on tetramer and ELISpot analysis. These are early data at early time points that will be confirmed and extended as we obtain additional patient samples.

But perhaps most encouraging is the composite view from the clinical experience thus far. We designed a novel biologics platform that appears to possess favorable properties pertaining to drug exposure in PD and also appears to be demonstrating monotherapy clinical activity. As we continue to obtain further supporting data from CUE-101, we are highly enthusiastic about the broad possible applications of the CUE-100 series. The data generated from CUE-101 clinical experience has the potential to derisk the entire CUE-100 series since the core IL-2 elements, coupled to the peptide HLA framework, remain constant.

Okay. I'd like to now move on to Slide 10 to remind you of the key features that we believe underscore the superior differentiation of the IL-2 based CUE-100 series over other IL-2 modalities that are out there. This slide has been presented before as a part of our corporate deck and highlights the important fact that the CUE-100 series can selectively deliver IL-2 to the relevant T cells, that is the tumor-specific T cells while minimizing the safety liabilities and broad effects of other T cell subsets, both the Tregs and the vast majority of the nontumor reactive effector T cell repertoire that all of us harbor.

This is in stark contrast to the not-alpha IL-2 variants that minimize the activity in Tregs but still act with equal opportunity on all other T cells, the vast majority of them have no relevance to tumor specificity. Furthermore, the core framework of the CUE-100 series can prime and expand T cells from a naive T cell repertoire, as also reported in our recent publication in Clinical Cancer Research last month. While the not-alpha IL-2 variants rely upon a preexisting antitumor T cell repertoire that must be present within the patient to derive benefit.

The next slide, Slide 11, highlights our immuno-oncology development strategy to exploit the fullest potential of the CUE-100 framework. The present clinical trial with CUE-101 provides us with a foundational proof-of-concept in an indication of unmet medical need. And as mentioned previously, 101 is positioned to potentially derisk the entire 100 series. We have thus positioned ourselves to maximize success for the CUE-100 series by exploiting the key strength of the immuno-STAT platform, which is modularity and flexibility that allows us to target different tumor antigens along with distinct HLA alleles for global patient populations. This strategic growth opportunity is exemplified from our current ongoing work with CUE-102 and beyond, where we have focused on tumor antigens like Wilms' tumor 1, or WT1, and KRAS and have initiated programs with additional alleles besides HLA-A*02. These include HLA-A24 and A11, both being dominant in Asia, which was the primary reason for our LG Chem partnership for our first 3 programs. We have made strong progress with our CUE-102 programs and have generated pilot data, demonstrating ex-vivo expansion of human T cells, polyfunctionality and their killing of target cells. These data were recently presented at an invited talk at the Frontiers in Cancer Immunotherapy meeting organized by the New York Academy of Sciences on May 12. We would also look forward to other avenues and forums to disclose these promising data sets, including the upcoming AACR virtual conference on June 22, where we will be presenting a poster.

Okay. So based upon the foundational work of our immuno-STAT platform, we have further developed our next-generation platform referred to as Neo-STAT, which greatly accelerates our scalability in generating new clinical candidates. The Neo-STAT framework specifically enhances our productivities and efficiencies, both from a time and cost perspective and builds upon our versatility to target multiple tumor antigens, including post translational modifications and personalized neoantigens in the future.

The next slide, Slide 12 focuses a bit more on the Neo-STAT platform. A key intellectual leap here was to design a platform enhancement that significantly expanded our reach into diverse tumor antigens. To remind you, the current immuno-STAT platform incorporates singular primary tumor driver antigens. This is great, for examples, like the HPV-16, E7 protein as in our lead molecule, CUE-101 or targets like WT1 or KRAS and such. In these cases, the immune assault to a dominant tumor driver antigen is likely to provide meaningful clinical benefit. Indeed, with all of the examples mentioned about data from cell therapy-based clinical studies, utilizing either TCR T cell therapy or TIL-based adoptive cell therapy have demonstrated clinical responses. However, looking into the future, we want to be positioned to capture the vast landscape of available tumor antigens. Tumor sequencing and profiling data emerging in real-time is providing us a continual source of new antigens that can be effectively deployed using our CUE-100 series. This is the thinking there is -- what propelled the Neo-STAT platform, wherein we can generate the entire CUE-100 series scaffold, without any specific peptide attached to the HLA molecule. And again, this is in stark contrast to the current Immuno-STAT platform, wherein each T cell epitope is an integral part of the Immuno-STAT, meaning it's incorporated into the molecule as a fusion protein at the time of synthesis. Neo-STATs are synthesized without a peptide epitope. Instead, the peptide epitope is actually attached subsequently using sophisticated attachment chemistry as shown in the current figure with the examples of 3 different peptides bound to the Neo-STATs' scaffold. This advance allows us to generate the core generic scaffold for any HLA allele via a single cell line and then use the same product to conjugate the different tumor antigens to expand our reach. The fact that only a single scaffold needs to be generated will save us significant resources in both time and cost for generation of clinical-grade material. And in doing so, provides us essentially with an off-the-shelf biologic to target T cells directly in the patient.

We have generated early proof-of-concept data supporting the biological activity of molecules generated via the Neo-STAT platform, and an example of one such dataset is shown in the following Slide 13. Additional data underscoring the protein engineering efforts were disclosed at a talk at the World Vaccine and Immunotherapy Congress meeting about 6 months ago, in December 2019 in San Francisco.

So moving on to Slide 13. The top panel here shows expansion of CMV specific T cells from 3 human donors. The bottom panel shows expansion of MART-1 specific T cells from additional 3 human donors. MART-1 is a known antigen in melanoma. In each case, the PBMCs from human donors were expanded with Immuno-STATs wherein the CMV or MART-1 T cell epitope is made as a fusion protein or with Neo-STATs wherein the respective T cell antigen is chemically conjugated to the scaffold.

As you can know, the expansion of relevant T cells specific for CMV or MART-1 was very comparable. The Immuno-STAT expanded T cells are shown in solid lines, while the Neo-STAT expanded T cells for each specificity are shown in dotted lines. These data provide enormous confidence that the Neo-STAT platform can be developed for future therapeutic applications and will complement and extend the current application of the Immuno-STAT platform. Note that the scaffold of the Neo-STAT described in the current slide is essentially the CUE-100 series without an antigenic peptide, but the same core configuration and valency of IL-2 molecules.

The next slide, Slide 14, highlights our pipeline progress. We've made significant progress with CUE-101 in the monotherapy trial, as discussed by Ken and Dan, and are positioned well for the combination study with pembrolizumab for later this year. CUE-102 with WT1 continues to make strong progress. To remind you, this program is being prosecuted with 2 different HLA alleles, HLA-A*02 and HLA-A24, which is a dominant allele in Asian populations. CUE-103 is being vetted currently with LG Chem, our Asia partner, and will be disclosed in the near future. And as listed here, we've also made meaningful progress with our KRAS program with the CUE-100 series. We will hopefully find an appropriate forum to share those data in the near future.

We continue to extend the application of our platform with the CUE-200 series, wherein we have early data sets with -- cell surface receptors like CD80, which is B71 that binds to CD28 in T cells and 4-1BB ligand. And finally, as disclosed recently, we continue to make strong progress in autoimmunity in our alliance with Merck using the CUE-300 series, wherein we have successfully generated Immuno-STATs incorporating class II HLA molecules to selectively target or to react to CD4-positive T cells in human patients. Selective modulation of an aberrant immune response in autoimmune diseases without broad immunosuppression, as is the case with current therapies, is likely to bring superior clinical benefit to patients. We believe this goal can be achieved with a platform like ours.

In conclusion, and as I've stated in prior presentations, the Immuno-STAT and by extension the Neo-STAT platform, address a fundamental immunological challenge, which is how does one maintain selectivity and specificity of a desirable immune response without breaching patient safety or creating toxicities. We believe our approach that is built upon rational protein engineering and is bolstered by supporting data set may offer a unique solution to patients suffering from cancers, autoimmune diseases and threats from chronic pathogenic infections.

Okay. With that, I'll now turn the call over to Kerri to review our financial results. Kerri?

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Kerri-Ann Millar, Cue Biopharma, Inc. - VP of Finance and Principal Accounting & Finance Officer [6]

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Thank you, Anish. Turning now to Slide 15. I'd like to provide a brief update on our financial results for the first quarter ending March 31, 2020.

We finished the quarter with approximately $48.7 million in cash and cash equivalents, $60.6 million in total assets and working capital of approximately $39.1 million.

Revenue generated from our collaboration with Merck and LG Chem in the first quarter of 2020 are at $0.9 million as compared to $0.4 million for the same period in 2019.

For the quarter ended March 31, 2020, research and development expenses were $9.9 million as compared to $8.4 million for the same period in 2019. The increase in research and development expenses was primarily due to clinical trial costs related to our ongoing CUE-101 monotherapy trial that was initiated in the latter part of the third quarter of 2019, and as well as manufacturing costs for CUE-101 to supply our recently announced combination trial of CUE-101 with Merck's KEYTRUDA.

General and administrative expenses were $3.9 million for the quarter ended March 31, 2020 as compared to $3.4 million for 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 first quarter of 2020. In April 2020, we extended our cash runway through the -- an at-the-market equity offering sales agreement for aggregate proceeds of $34.3 million, net of commissions paid to Stifel, who acted as sales agent. The successful deployment of the ATM facility in April has enabled us to strengthen our cash position to further support the development of our Immuno-STAT platform and associated pipeline, including the clinical development of CUE-101 as both in mono and combination therapy.

Based upon our current forecast, which includes the further build-out of our ongoing clinical studies, our current cash position is estimated to take us into the fourth quarter of 2021.

With that, I'll turn the call back over to Dan for closing remarks. Dan?

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Daniel R. Passeri, Cue Biopharma, Inc. - CEO & Director [7]

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Yes. Thanks, Kerri. Yes, since our last call, and despite the challenges we continue to face by the COVID-19 pandemic, we've made significant progress across our platform and associated programs, as I'm shown here in Slide 16. Having raised additional capital in April and having enrolled in treated patients through cohort 3 and now into cohort 4 in our CUE-101 Phase I trial, we're now better positioned strategically to continue advancing CUE-101 for determining a recommended Phase II dose as a monotherapy and into a combination trial with KEYTRUDA and as well as further advancing our platform and the associated programs.

As just described above, our lead program, CUE-101 is well positioned to generate a body of data, including PD biomarker activity and patient scans that demonstrate biologic and clinical activity. In this patient setting, these data would significantly derisk and validate our approach. Allowing us to further build our pipeline based upon the same foundational principles upon which we bought CUE-101 forward. With CUE-101 now being dosed at what could be biologically active and clinically relevant levels, we believe we are very well positioned to establish Cue Biopharma as a differentiated leader in immunotherapy with a potentially disruptive breakthrough therapeutic platform. A couple of our key accomplishments in Q1 include continued and timely enrollment of cohorts 1 through 4 in the CUE-101 monotherapy trial, along with demonstration of favorable safety and tolerability, dose proportional exposure in line with preclinical projections and early signs of PD activity in emerging clinical activity.

Our guidance for 2020 milestones, as shown on Slide 16, are unchanged from our last call. And principally, they are PK and PD results from the Phase I CUE-101 clinical trial in the second quarter of 2020, and we've demonstrated that is on track today. Clinical responses in Phase I for CUE-101 via resist criteria in the second half of this year, we're already beginning to see what appears to be emerging data supporting that. Initiate a combination trial with KEYTRUDA in first-line, head and neck squamous cell carcinoma patients in the second half of this year, and we're on track with that with the announcement of the consummation of the partnership with KEYTRUDA. Initiate and extend IND-enabling activities for CUE-102 in the second half of this year, we're on track. And selecting a defined target for CUE-103 in the second quarter of this year, and we are on track for that in discussions with our partner, LG Chem. Demonstrate Neo-STAT manufacturability and efficiencies in the second half of 2020, and as you heard from Anish, we've made quite significant progress towards that objective. And then finally, identify potential clinical candidates in our autoimmune collaboration with Merck in the second half of this year.

So with that, I'd like to, once again, thank our employees for their hard work and commitment to advancing our science forward during these challenging times. And finally, I'd like to thank our shareholders, and our Board of Directors for continued support, enabling us to advance Cue Biopharma's platforms towards validation in the clinic while also moving our preclinical assets closer to IND-enabling studies. We look forward to providing further updates on the validation, growth and expansion of our pipeline, including our CUE-101 Phase I trial. And most importantly, we're grateful to all who enable us to pursue this noble mission to serve patients in need.

I'd like to now open the line for questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Boris Peaker with Cowen.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [2]

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So my first question is, so in the party of the study, the design allows you to expand doses out to 9 patients if you see activities. Just curious if you've expanded any or if you plan to expand any doses by -- based on the initial activity that you're observing?

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Daniel R. Passeri, Cue Biopharma, Inc. - CEO & Director [3]

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Sure. Ken, why don't you take that?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [4]

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Yes. Thanks for the question, Boris. So yes, we are planning to expand. Based on our Bayesian approach, we have not yet started to expand because we've been focusing on escalation. Since we have not reached a DLT, we've made the conscious decision to continue to dose escalate prior to expanding at any given dose level but we're constantly evaluating that. But the short answer is we have not started to expand any of the lower cohorts as of yet.

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Boris Peaker, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [5]

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Got you. And my second question, in terms of the dose escalation, I mean, your plan has 7 cohorts right now kind of estimated or, I guess, per protocol. I'm just curious, at some point, if you get to the seventh cohort and the drug is still tolerated, is there thoughts of going higher? Or how do you kind of think about the highest dose level or testing and dose range, considering you have an agonist versus most of the time we're used to thinking of antagonist?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [6]

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Yes. So that's a great question. And that's why we really built in this Bayesian approach to look -- to really evaluate what types of responses we're having, both clinically as well as by PD biomarkers and we fully expect that by dose 7, we're going to be seeing those types of biologic and clinical markers that would allow us, even if we haven't seen toxicity to expand out at these lower cohorts. I seriously doubt we'll have to go higher than dose 7, but we're prepared to. But the reason we built in this overlying Bayesian approach over the 3x3 design was really to -- because we were concerned that we would not see a dose-limiting toxicity, and we want to be able to pick a rational dose for the Part D dose expansion. So I think before -- as long as we're seeing PD and clinical effects, we're likely to use our expansion of these lower cohorts to allow us to pick a Phase II, what we think is going to be the recommended Phase II dose without going necessarily higher.

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Operator [7]

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Our next question comes from the line of Stephen Willey with Stifel.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [8]

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Maybe a couple of questions for Ken. So you mentioned, I guess, an infusion reaction is happening. I think it was maybe cohort 3. Has --

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [9]

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No, it was cohort 4.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [10]

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It was cohort 4. So can you maybe just talk about the severity of the AE that was observed there? And do you think you might have to premedicate as you move higher?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [11]

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Yes. So it was an SAE and not an -- not a DLT. And the patient -- it was rapidly resolved over the space of an hour basically. And it required -- the patient did get some ibuprofen but there was -- we -- the investigators have discussed it, we've discussed it. At this point, we don't believe -- we're not planning on premedicating at the next dose level. And I have no indication right now that we would have to do that. Again, this is not a sustained SAE that leads -- would lead us to change what we're doing at this point.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [12]

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Okay. No, that's helpful. And then just curious as to when in the time course of treatment are you evaluating T cell expansion and activation in these patients? How soon after administration?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [13]

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So we're looking at -- we look at -- I'm not quite sure I understood the question. I'm sorry.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [14]

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So just curious as to when you're assessing these patients for peripheral T-cell expansion and activation. How soon after administration are you looking at?

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [15]

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Right. So maybe I can comment on that. This is a Anish, Steve. So the first, as you will remember, the cycle is a 3-week cycle. So the drug is given, And the first analysis are over the first couple of weeks, then at each of the cycles, before the drug is given, we're able to look at the T cells. So there's a couple of weeks time lag between the dose of the drug and the time we get the blood for the analysis. And again, as Ken pointed out and as I stressed, these are early time points. So we need to build this out with additional time points and additional doses and additional patients. So these are early signals that we've started to measure at this point.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [16]

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Okay. And then you mentioned that you're continuing to treat 5 patients, I think I heard. So it sounds like that might be the 1 cohort, 2-patient that's had a confirmed stable disease. Can you maybe just kind of directionally point us to where those other patients are in terms of cohorts?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [17]

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Sure. Sure. So we have the 1 patient from cohort 2. We have another patient from cohort 3 and then the 3 patients from cohort 4.

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Stephen Douglas Willey, Stifel, Nicolaus & Company, Incorporated, Research Division - Director [18]

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Okay. And then maybe just lastly, do you kind of feel like you have enough information at this point just based on where you are in dose escalation to initiate the PD-1 combo dose escalation in parallel? Or do you want to push dose a little bit higher before you get that going?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [19]

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Well, we really want to push the doses a little higher before we get that going. We wanted to be sure that we have enough information in the monotherapy arm to be able to pick a dose because we would like to pick a dose that's high enough that we can start to see early and immediate effects in the combo. And so we did offset the combo to start in the second half of this year rather than right away and we did suggest that we would start at least at a minimum of cohort 3 with the combo, but it may -- we're hoping that we can potentially even go higher. So in our submission to the FDA, we said at least that we put in cohort three, but we also have the option of changing that.

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Operator [20]

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Our next question comes from the line of Mark Breidenbach with Oppenheimer.

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Mark Alan Breidenbach, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [21]

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And congrats on the forward progress with dose escalation and especially on the early signs of tumor regression, in sounds like some, of the patients. Let me ask, for the patients who have shown some early indications of tumor regression, have they all progressed on prior PD-1 therapy? Or were any of them only previously treated with chemo?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [22]

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Yes, Mark, thanks for the question. This is Ken. All of the patients have been heavily pretreated, including with checkpoint inhibitors. So they've all progressed on checkpoints.

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Mark Alan Breidenbach, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [23]

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Okay. And so can you comment, is there a protocol mandated PD-1 washout period? And maybe can you just give us some color on the interval between the last PD-1 dose and the start of CUE-101 for these patients?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [24]

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Yes. So that's a really great question. And there is no mandated washout period per se. All we are requiring is that patients are progressing. The different -- so every patient has a different length of time that they've been off PD-1 checkpoint type therapy. The -- in general, that's at least 2 to 4 months of -- from their last dose.

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Mark Alan Breidenbach, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [25]

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Okay. Okay. That's helpful. Maybe a quick one for Dan. I'm just wondering if we can expect the more fleshed out PK/PD data to make an appearance at a medical meeting in the second quarter? Or are you thinking this will be delivered via press release once you have enough follow-up on these patients?

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Daniel R. Passeri, Cue Biopharma, Inc. - CEO & Director [26]

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Sure. I'll answer that sort of as an overview, and I'll ask Anish to elaborate. But look, we're going to be opportunistic about it. We're not going to hold on data, waiting for a conference unless we already have it lined up and the timing aligns. So -- and we won't put out a press release unless we think it's substantively warrants that type of release. So our intention is to compile data as we've been doing. Obviously, we're using the quarterly calls as a venue. But at various conferences, and also we have investor conferences that we have the opportunity to update on an intermittent basis. So in this sort of COVID-19, new normal that we're dealing with, we'll use virtual venues where applicable, our web page and press releases as appropriate. I don't know if you want to...

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [27]

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Yes. I think that's right, Mark. I mean, we ourselves getting acquainted to the new normal. As I mentioned, even with the WT1, for example, we have that at AACR that's now going to happen in June. But we will certainly be looking for appropriate forums where we can thoughtfully compile the data and share at these meetings. And of course, later in the year, we've got opportunities with SITC and such, but we look at ones before that too, and that's something that we continue to sort of discuss amongst ourselves that can -- we'll find those opportunities.

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Mark Alan Breidenbach, Oppenheimer & Co. Inc., Research Division - Executive Director & Senior Analyst [28]

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Okay. And just a quick follow-up on the AACR presentation on, I guess, CUE-102, are we going to see any data in that presentation that might give us more of an indication on which types of tumors you initially intend to focus clinical development on for CUE-102?

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [29]

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So the AACR presentation, Mark, where WT1 is focused on characterization of the molecules and the early data that we've seen with primary human T cell and the downstreaming factor responses, which are very encouraging. As for the indications, this is something that Ken and the team are -- we -- this is sort of one of our core priorities this year, is to align and define those. And as you well know, in contrast to HPV-driven head and neck cancer where E7 stratified nicely, WT1 has a spectra of hematological and solid cancers, and there's a few of them that stand out. And the team is continuing to sort of flesh that out. And we'll be able to hopefully share with that -- those sort of thoughts in the later half of this year is what I'd imagine. We'd have that plan sorted out for a clinical -- for clinical development strategy in how we apply this molecule.

Also in contrast to 101 where the allelic variant is A*02, the WT1 program is being developed with A*02 for this part of the world with A24 for the Asian territories, as I mentioned, with obviously different T cell epitopes, that also provides a breadth of opportunity in different geographies.

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Operator [30]

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Our next question comes from the line of Madhu Kumar with Robert W. Baird.

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Madhu Sudhan Kumar, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [31]

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So I think our first one is kind of maybe scientific and philosophical. It's really for Ken and Anish. So how long do you think it practically takes to educate T cells activated against HPV-E7 from CUE-101? And then kind of following from that, do you think the time line for T cell activation that you're observing so far, is consistent with kind of naturally already present HPV directed T cells kind of emerging out of the milieu or representative of kind of people that really have to be kind of trained de novo to engage with in going after HPV-E7?

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [32]

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Yes. I'll take a crack at it, Madhu. That's an excellent point, which is the kinetics of the evolution of a T cell response as a function of the pre-existing repertoire. So the point that you brought up is a very important one and it entirely depends on what the baseline composition is. If you haven't sensitized and you're going from a naive virgin repertoire, then obviously, the time to effect is going to be longer than if you are going to be expanding from a pre-primed repertoire. And that was the case. We also stressed in the paper that we published last month, where you could see nuances in intensity and presence, depending on whether you had a pre prime repertoire or not. My bias as an immunologist is these first signals that we've seen from the patients after the first few doses are likely from ones that have some presence in the periphery. And I think that goes to say that in the longer run, there may be patients that may need a little bit more time on drug to perhaps exhibit similar peripheral signals. That's just the periphery. And again, I come back to the central question that this is -- we look at the peripheral blood as a surrogate for the lesional tissue. In case there are scenarios, where you have resident populations that have honed into the tumor, not so much present in the periphery, one may expect to disconnect but you may not see much in the periphery, but you may start to see certain tumor lesion-specific activities. And that's something we've got to just keep an open mind because ultimately, what the effector site is harboring is still an open question. And you could have resident cells against the very dominant antigen that are parked there, that are held back for whatever local resistant mechanisms are there. That could be engaged by the drug. We know that the molecule can get to the tumor effector site in our preclinical models, the degree of tumor resident expansion was significantly higher when we measured the tumor-specific T cells as opposed to the periphery. But all those which you bring up are excellent nuances of experimental immunotherapy that we're aware of. And as the data emerges, we'll be able to sort of hopefully put some solid cohesive structures around these thinking.

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Madhu Sudhan Kumar, Robert W. Baird & Co. Incorporated, Research Division - Senior Research Analyst [33]

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Okay. Also following from that question, to think about the kind of molar equivalent descriptions you just -- have given, have you done kind of exposure equivalent, given if the your drug is much more persistent than Proleukin is kind of in circulations?

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [34]

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So as -- we just -- we need to get some more exposure data. These are early points, Madhu, and we'll be able to put that in perspective. And that is the intention. We were very encouraged to see that the early exposure looks in line with what was projected, but the Proleukin exposure is very different than ours. And that's a factor that needs to be further fleshed out as we get additional exposure data from the higher dose groups, but that's a very good point.

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [35]

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Yes. And we also recognize that these doses that we are showing are based on a single dose of Proleukin and of course, how much of the toxicity of Proleukin is due to the multiple doses that you need to give to get exposure.

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [36]

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So that's a very good point that Ken just made. Yes.

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Operator [37]

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Our next question comes from the line of Ren Benjamin with JMP Securities.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Equity Research Analyst [38]

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Maybe just starting off, a question for Ken. If I just look at cohorts like 1 through 3, 9 patients. If I heard you right, there were 2 SDs and 2 patients with T cell expansions or activations. And I'm -- and if that's right, I'm kind of curious, why wouldn't the 2 patients with the T cell expansions also be the ones who are getting the SDs? Just kind of your thoughts on that. And what's the longest SD that you've recorded to date?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [39]

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So I think that some of these patients, what we've seen is that these patients are all rapidly progressing. And the fact that we've seen anything at all at these low doses is pretty tantalizing to me personally and to all of us. And I think what we've seen is that we've started to see some TV effects and what looks to be early expansion activation, but that -- it's just not been enough to overcome patients with basically exponentially growing tumor and at these low doses, we just haven't been able to see a sustained response even in the patients who are starting to show us some biologic activity. So the -- if you look at our longest stable disease patient, what we've had is exactly -- or we have one patient who is through cycle -- is cycle 5, and we have to get to at least -- to confirm a response, we have to get at least through 4 -- cycle 4. So we've had 2 patients that have made it through to cycle 5 dosing.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Equity Research Analyst [40]

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Got it. And just -- I know it's early days, but I'm kind of curious, when you look at the other patients, are there any negative selection metrics or biomarkers that maybe are starting to pop out? Or you guys are starting to evaluate maybe even something like T cell exhaustion markets, right, that you might be able to utilize moving forward? Or do you kind of feel that, you know what, once we start moving into less heavily pretreated patients, we think that the repertoire is going to be healthy enough that it's not really going to be an issue in terms of patient selection?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [41]

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Yes, that's a great question. I think we just -- we don't have enough data yet on exhaustion, and we're certainly looking into and have plans in the protocol to evaluate those types of biomarkers to try to understand who is not responding. I do think moving into earlier groups, like we are with the combo study, which will be also a dose escalation study, by the way, we'll be able to see patients who don't have exponentially growing tumor and we'll have a little bit more time with those patients to have an effect, and I think that's going to be critical. But I also think that, again, choosing -- why do -- trying to understand why the checkpoints fail. And in combination, if we're not having a good response. I think we are going to see some -- using TPS scores, et cetera, we're going to be able to start to get a feel for why CUE-101 might not be working. So we're thinking hard about that. We've got some biomarkers built in. And we're looking forward to treating earlier patients.

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [42]

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Yes. Ren, just to add on to what Ken said, I think one of the parameters of immune fitness in terms of looking at the repertoire, the induction part of our biomarker panel that we'll get to evaluate, it's just a point of collecting and having more data. I think fundamentally, what's quite remarkable is you've got a novel protein framework going for the first time in man and the fact that it is inducing the appropriate, what we think is the right repertoire to us is very encouraging, obviously. The fact that the IL-2 at these high doses is being sustained and tolerated with the appropriate safety parameters, again, becomes very important. And as you well pointed out, whether that also then co-emerges with other metrics, that we've started to see is a component that we are very much -- we're looking forward to studying. The relationship between the PD metric and clinical response, in terms of absolute numbers, I mean, I just want to be very careful there because ultimately, what's going to matter is what is the infiltrator at a tumor lesional site, what is the phenotype of the infiltrating repertoire, what may be local resistant mechanisms we may need to consider. To that end, the combination with pembro makes very good sense. But I think as we gather more data in all of these wonderfully relevant immunological parameters, I think we'll hopefully get addressed.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Equity Research Analyst [43]

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Got it. And just regarding the PK/PD results that we're still expecting this quarter, I know originally, correct me if I'm wrong, I thought originally, we were thinking about cohorts 1 and 2, but enrollment seems to be going so well. Is it fair to say that when we're looking at these PK/PD results, it will likely be cohorts 1, 2 and 3? Or, no be expecting on...

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [44]

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Yes. I think -- so I think our expectations and the way this is something that's ongoing, when we can share that our exposure data, the early exposure data from cohort 3, we anticipate to have it by the end of this month. So our hope is -- and as you pointed out, the fact that we've continued to see enrollment, and we will continue to sort of dose escalate, that as we start to gather more of these data and put it out that it should have a composite body that goes beyond 1 and 2. We're very excited about that.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Equity Research Analyst [45]

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Got it. And I guess, what...

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [46]

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I would just like to -- I was just going to add in here that we are so grateful. Again, as I mentioned in the call, that we're so grateful that we've been able to continue to enroll. We are hyper aware that 90% of all cancer trials are not enrolling right now across these academic institutions. And again, the fact that we've been able to -- our investigators having convinced their institutions that we are a critical drug that should be allowed to enroll, it was a real testament to how important they think this is. And I'm just -- as an academic investigator myself, I am thrilled that we've be able to enroll through this. So thanks.

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Reni John Benjamin, JMP Securities LLC, Research Division - MD & Equity Research Analyst [47]

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No, that makes sense. I guess, one last question, I don't want to leave Dan out of the discussion here, but you've got a really nice significant cash position now. And you can -- I guess, I can sort of think about it in 2 ways. One is it could result in an acceleration of the pipeline and things that we were expecting, might take a year or 2 coming in a little bit earlier? Or that at this stage in the game, there are enough kind of rate limiting steps, like maybe manufacturing or no matter how much cash you throw at it, it's not necessarily going to speed up the time lines. How should we be thinking about kind of the usage of cash and the acceleration of the pipeline?

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Daniel R. Passeri, Cue Biopharma, Inc. - CEO & Director [48]

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Yes. It's a really important question, Ren. And by the way, I appreciate your perspective on no matter how much you throw at it, because a lot of companies think by just hiring more people, they can increase output. Scale requires rigor, right? And that's what we've been putting in play, laying the foundation over the past year plus, and we look at the data emerging from 101 as a validator of what the 100 series could represent. So as we continue to data -- generate more data such as what you've heard today but on a going-forward basis with more patients, our intention is to then, we can expand out with 101, we have to advance 102. And as Anish described earlier, Neo-STAT is meant to be a platform advancement. To be able to exploit these observations in a, let's say, more productive, cost-efficient manner. So it's a hybrid between what you articulated. We're not going to be conservative and just continue systematically building data on 101 and wait on everything else. But we're also not just going to start increasing our burn rate. We're going to do this in a very deliberate, purposeful trajectory. The first thing is to generate derisking, validating data with 101 which can then justify increasing expenditure on other assets that benefit from that derisking. So that's the way we're basically approaching this.

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Operator [49]

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Our next question comes from the line of Tom Shrader with BTIG.

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Thomas Eugene Shrader, BTIG, LLC, Research Division - MD & Healthcare Analyst [50]

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So going back to what was a very interesting line of discussion about, the T cells may actually need to be in the periphery for you to have time to work. Do you measure that? Can you get an accurate read on the T equals 0 T cells that might respond to your antigen?

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [51]

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Yes. Tom, so whenever these analyses are done, they're always compared to the baseline from the blood pre-dose. So you have a sense of what that snapshot looks like. You're using that as the baseline to judge an uptick and that's how you're going to be quantifying it, just to get a sense that have you induced the rights to the kind of repertoire or not.

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Thomas Eugene Shrader, BTIG, LLC, Research Division - MD & Healthcare Analyst [52]

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But can you sort of back extrapolate now that it has to start here to have a chance of being an anti-T cell response given the common...

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [53]

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No. That actually is -- that -- those sorts of hard numbers can be put in inbred species in experimental animals but when you get to the population at the level of the species of human, those numbers all over the place, simply because you have different levels of sensitizations, you have different diversity of the repertoire, and don't forget, through the treatment regimens that these patients have been through, the immune competence and fitness criterias are -- may be quite variable. So that -- you can do it on a per individual basis, but it's -- I think it'd be very difficult to bracket it as a group basis.

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Thomas Eugene Shrader, BTIG, LLC, Research Division - MD & Healthcare Analyst [54]

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And then maybe the same question. Were your people -- that you treated all over the place in terms of their prior PD-1 response? And is there anything interesting to think about between what they got out of PD-1 and what they got out of your approach?

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Anish Suri, Cue Biopharma, Inc. - President & Chief Scientific Officer [55]

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So I think Ken mentioned that almost -- I think Ken mentioned this just a few moments ago that almost all of them are prior checkpoint failures. And again, that comes back to the central point, Tom, which is if you fundamentally don't have the right effect on repertoire or the appropriate specificity locked in, the application of a checkpoint is not very relevant. I mean, the checkpoint is working with the assumption that you've got the repertoire in there. So 1 of the questions for us as we gather more data is to understand those very relationships. And hopefully, as some of these clinical responses solidify, one can perhaps establish those relationships. And if that's true, then the combination with KEYTRUDA should further build upon that and should have what we think could be quite a remarkable outcome in the sense that you've got an agent that's inducing the right repertoire in a very selective, stable manner, coupled with if they should upregulate PD-1, they should gain benefit from that angle. But having just a PD-1 blocker in absence of the repertoire doesn't do much.

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [56]

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It's Ken, I would just note that none of the patients had a sustained checkpoint response before going on study.

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Thomas Eugene Shrader, BTIG, LLC, Research Division - MD & Healthcare Analyst [57]

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Okay. So they were like primary failures, they just blew right through PD-1?

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Kenneth J. Pienta, Cue Biopharma, Inc. - Acting Chief Medical Officer [58]

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Pretty much blew right through, yes.

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Operator [59]

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There are no further questions in the queue. I'd like to hand the call back to management for closing remarks.

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Daniel R. Passeri, Cue Biopharma, Inc. - CEO & Director [60]

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Okay. Thank you very much. Also, I want to thank everyone for your time and attention. And for your interest and support of Cue Biopharma. We look forward to giving you continual updates as they become available. And most importantly, we hope everyone stays safe and healthy during these challenging times. So thank you very much, and take care, everyone.

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Operator [61]

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Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation. You may disconnect your lines at this time, and have a wonderful day.