# Cue Biopharma, Inc.: Form 10-Q for the period ended Sep 30, 2024 - Company: [Cue Biopharma, Inc.](/companies/cue.md) (CIK 1645460) - Form: 10-Q - Filed: 2024-11-14 - Accepted by EDGAR: Nov 14, 2024, 21:00 ET - Period: 2024-09-30 - Accession: 0000950170-24-127005 - Inline XBRL: yes - Main document: https://www.sec.gov/Archives/edgar/data/1645460/000095017024127005/cue-20240930.htm - All documents and exhibits: https://www.sec.gov/Archives/edgar/data/1645460/000095017024127005/ ## Figures reported in this filing Standardized XBRL line items for the period ended 2024-09-30. | Line item | Period | Value | XBRL concept | | --- | --- | ---: | --- | | Revenue | 3 months, 2024-07-01 to 2024-09-30 | $3.3m | us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax | | Revenue | 9 months, 2024-01-01 to 2024-09-30 | $7.7m | us-gaap:RevenueFromContractWithCustomerExcludingAssessedTax | | Research and development | 3 months, 2024-07-01 to 2024-09-30 | $9.4m | us-gaap:ResearchAndDevelopmentExpense | | Research and development | 9 months, 2024-01-01 to 2024-09-30 | $29.1m | us-gaap:ResearchAndDevelopmentExpense | | Operating income | 3 months, 2024-07-01 to 2024-09-30 | −$8.8m | us-gaap:OperatingIncomeLoss | | Operating income | 9 months, 2024-01-01 to 2024-09-30 | −$31.9m | us-gaap:OperatingIncomeLoss | | Net income | 3 months, 2024-07-01 to 2024-09-30 | −$8.7m | us-gaap:NetIncomeLoss | | Net income | 9 months, 2024-01-01 to 2024-09-30 | −$31.2m | us-gaap:NetIncomeLoss | | Diluted EPS | 3 months, 2024-07-01 to 2024-09-30 | −$0.17 | us-gaap:EarningsPerShareDiluted | | Diluted EPS | 9 months, 2024-01-01 to 2024-09-30 | −$0.62 | us-gaap:EarningsPerShareDiluted | | Basic EPS | 3 months, 2024-07-01 to 2024-09-30 | −$0.17 | us-gaap:EarningsPerShareBasic | | Basic EPS | 9 months, 2024-01-01 to 2024-09-30 | −$0.62 | us-gaap:EarningsPerShareBasic | | Diluted shares (weighted) | 3 months, 2024-07-01 to 2024-09-30 | 51,229,701 shares | us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding | | Diluted shares (weighted) | 9 months, 2024-01-01 to 2024-09-30 | 50,292,983 shares | us-gaap:WeightedAverageNumberOfDilutedSharesOutstanding | | Operating cash flow | 9 months, 2024-01-01 to 2024-09-30 | −$27.3m | us-gaap:NetCashProvidedByUsedInOperatingActivities | | Capital expenditure | 9 months, 2024-01-01 to 2024-09-30 | $64.0k | us-gaap:PaymentsToAcquirePropertyPlantAndEquipment | | Cash and equivalents | at 2024-09-30 | $32.4m | us-gaap:CashAndCashEquivalentsAtCarryingValue | | Current assets | at 2024-09-30 | $37.3m | us-gaap:AssetsCurrent | | Total assets | at 2024-09-30 | $44.8m | us-gaap:Assets | | Current liabilities | at 2024-09-30 | $16.8m | us-gaap:LiabilitiesCurrent | | Total liabilities | at 2024-09-30 | $19.4m | us-gaap:Liabilities | | Long-term debt | at 2024-09-30 | $1.3m | us-gaap:LongTermDebtNoncurrent | | Current portion of debt | at 2024-09-30 | $4.0m | us-gaap:LongTermDebtCurrent | | Shareholders' equity | at 2024-09-30 | $25.4m | us-gaap:StockholdersEquity | ## Management's discussion and analysis As filed, 70,978 characters. *The following Management’s Discussion and Analysis of Financial Condition and Results of Operations of Cue Biopharma, Inc. and its subsidiary (“Cue Biopharma”, “we”, “us”, “our” or the “Company”) should be read in conjunction with our financial statements and accompanying notes included in this Quarterly Report on Form 10-Q and the financial statements and accompanying notes thereto for the fiscal year ended December 31, 2023 and the related Management’s Discussion and Analysis of Financial Condition and Results of Operations included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission, or SEC, on March 28, 2024, or the 2023 Annual Report.* ### Overview We are a clinical-stage biopharmaceutical company developing a novel class of therapeutic biologics to selectively modulate disease-specific T cells directly within the patient’s body. Our vision is to translate nature's signals, or "cues", into clinically active and well tolerated protein therapeutics by generating a new class of T cell engagers for selective modulation of disease specific T cells. We believe our proprietary Immuno-STAT™ (*Selective Targeting and Alteration of T Cells*) platform and derivative molecules, as described below, will enable us to enhance the potential of the patient’s own immune system to restore health while avoiding the deleterious side effects of broad immune activation, in the case of cancer, and broad immune suppression, in the case of autoimmune disease. Our selective immune modulation approach may be deployed for treating two of the major diseases causing debilitating human suffering and mortality, namely cancer and autoimmune disease. Cancer and autoimmune disease are major areas of disease affecting large populations across the globe, shortening the life expectancy of those afflicted, and significantly affecting quality of life. There are approximately 20 million new cancer diagnoses worldwide each year with approximately 2 million in the United States, or U.S., alone. Of these new cases, approximately 50% will progress to recurrent metastatic disease ultimately resulting in death. In addition, approximately 4% of the world’s population is diagnosed with an autoimmune disease resulting in approximately 24 million cases in the U.S. alone. Recognizing that T cells, as the heavy artillery of the immune system, are regulated with a highly selective “command and control” instruction process through interactions with the antigen-presenting cells, we have engineered the Immuno-STAT platform to emulate this “command and control” system. Specificity, or the "control" in the “command and control” system, is achieved through the T cell receptor, or TCR, binding to a specific, targeted epitope, depicted by the yellow circle in the figure on the right below, along with a “command” co-stimulatory signal, such as interleukin 2, or IL-2, depicted as the purple pentagon in the figure on the right below. These two “cues”, or signals, when engaged concurrently, as is the case with our Immuno-STATs, are able to “dial-in” selective activation of targeted tumor-specific T cells to attack cancer while avoiding potentially harmful broad immune activation of T cells. Conversely, in autoimmunity, our autoimmune drug product candidates are designed to deploy inhibitory signals to selectively dampen autoreactive T cells while avoiding broad immune suppression that can increase susceptibility to other diseases. The figure to the left below depicts the interaction of the antigen presenting cell, or APC, with a specific T-cell as seen in nature. #### Immuno-STAT Platform: Emulating Nature’s Selectivity Our first two oncology drug product candidates, currently in clinical development, CUE-101 and CUE-102, are exemplary programs from the IL-2 based CUE-100 series, and are representative of the HLA-A02 allele, which is the predominant human leukocyte antigen, or HLA, allele in the U.S. and western European territories, i.e., approximately 50% of the patient population, and also prevalent, albeit at lower frequencies, in other global populations. We have preclinically validated the targeting of T cells with additional HLA alleles, which could enable expansion of patient coverage globally for future drug product candidates. CUE-101 is engineered for the treatment of human papillomavirus positive, or HPV+, head and neck squamous cell carcinoma, or HNSCC. By changing the epitope 9-amino acid sequence depicted as the yellow circle in the above illustration, we developed CUE-102, targeting Wilms’ tumor 1 protein, or WT1, an oncofetal antigen known to be over-expressed in more than 20 different cancers. Based upon the clinical observations to date, we believe we have demonstrated that our Immuno-STAT platform can be deployed across a wide spectrum of cancers by selectively activating the patient’s own immune system to combat cancer. Furthermore, we believe that the data generated to date, and continuing to mature, underscores what appears to be a substantial extension of survival, evidenced by the median overall survival, or mOS, of multiple patient cohorts receiving CUE-101 as a monotherapy, as well as in combination with the standard of care for HPV+ HNSCC, which we discuss in greater detail below under the heading “CUE-101”. We have also developed drug product candidates designed to address a broad spectrum of autoimmune disease by dampening or turning off self-reactive T cells that attack a patient’s body. We have a strategic collaboration with Ono Pharmaceutical Co., Ltd., or Ono, focused on the development of CUE-401 for the potential treatment of a wide spectrum of autoimmune disease through the induction and expansion of regulatory T cells, or Tregs. Furthermore, we have also developed a drug product candidate, CUE-501, for targeting B cell mediated autoimmune diseases, such as systemic lupus erythematosus, which would potentially enable autoreactive B cell ablation followed by natural repopulation thus restoring immune balance. Our drug product candidates are in various stages of clinical and preclinical development. The ongoing generation of clinical data for CUE-101 and CUE-102, as well as the emerging preclinical data for CUE-401 and CUE-501 continues to bolster our belief that we have developed a modular and versatile approach for “restoring immune balance” representing a potential breakthrough for enhancing clinical outcomes for patients suffering from cancer and autoimmune disease. ### Current Programs Historically, we have focused the majority of our resources on our CUE-101 and CUE-102 programs for oncology, representative of our approach for selective T cell activation against cancer. These programs have demonstrated evidence of selective T cell activation, proliferation and antitumor activity and continue to yield maturing clinical data, for what we believe may be a significant differentiation that supports further development towards potential registration with third-party support. Furthermore, we believe the maturing data has the potential to further validate the CUE-100 series, enabling the Immuno-STAT platform’s modularity and versatility to foster potential development of future drug candidates addressing a broad range of cancers. As the CUE-101 and CUE-102 programs continue to be monitored and provide maturing data, our primary current emphasis and resource deployment has been focused on our autoimmune disease programs, which we believe represent large market opportunities by addressing significant unmet medical needs. In July 2024, we announced a strategic prioritization of our autoimmune programs along with organizational restructuring to strengthen operational efficiencies and enable the already encouraging clinical data from our oncology programs to continue to mature and potentially further differentiate our competitive advantage, particularly pertaining to patient survival. As we shift our focus towards the development of our autoimmune programs, we continue to actively pursue third party support through partnerships and collaborations to further develop the CUE-100 series programs, including CUE-101 and CUE-102. As such, we have continued to progress forward in our strategic collaboration with Ono to develop CUE-401, a preclinical IL-2/transforming growth factor beta, or TGF -beta, bispecific based drug product candidate for autoimmune disease. Based on its unique mechanism of action, we believe CUE-401 has the potential to be a highly differentiated molecule for the induction and expansion of Tregs in a manner distinct from other IL-2 muteins that are being pursued in this space. In addition, we have advanced CUE-501, which targets autoimmune diseases caused by autoreactive, or self-reactive, B cells, into preclinical development. ### Oncology Programs ### CUE-101 CUE-101 is our most advanced clinical stage asset and is being investigated for the treatment of HPV+ HNSCC in patients with the HLA allele, HLA-A02. Our Phase 1 clinical trial is investigating CUE-101 in the treatment of HPV+ recurrent metastatic, or HPV+ R/M HNSCC as a monotherapy and in combination with KEYTRUDA. We received Fast Track Designation of CUE-101 for the treatment of HPV+ R/M HNSCC, as both a monotherapy in second line or higher, or 2L+, patients and in combination with KEYTRUDA, the current standard of care, or SoC, for first line, or 1L, HPV+ R/M HNSCC patients. We also have an ongoing investigator sponsored clinical trial in the neoadjuvant setting where tumor tissue is being analyzed before and after treatment with CUE-101. The preliminary data from pre- and post- CUE-101 treatment biopsies in this study demonstrated changes in the tumor microenvironment that are consistent with CUE-101’s proposed mechanism of action. This series of trials enables CUE-101 to be investigated in multiple patient populations with the objective of developing a deeper understanding of the drug candidate’s activity as well as enhancement of competitive positioning for establishing broad market opportunities. Both the CUE-101 monotherapy trial in 2L+ HPV+ R/M HNSCC and CUE-101 trial in 1L in combination with KEYTRUDA have completed patient enrollment and have demonstrated evidence of meaningful clinical activity. Most notably in our ongoing Phase 1b trial of CUE-101 in combination with current SoC, KEYTRUDA, as described in more detail in our 2023 Annual Report, we have observed one confirmed complete response and ten confirmed partial responses, as well as seven patients with durable stable disease (greater than 12 weeks) resulting in an objective response rate, or ORR, of 46% and a disease control rate of 75% as of the September 11, 2024 data cut-off date. This ORR represents a greater than doubling of the historical ORR of 19% that was observed with KEYTRUDA alone, as reported in the KEYNOTE 048 study. Importantly, these responses include multiple patients with low PD-L1 expression (combined positive score, or CPS, of less than 20), a patient population known to be less likely to respond to KEYTRUDA. Notably, low CPS has been documented in approximately 50% of all HPV+ R/M HNSCC patients eligible for KEYTRUDA in the 1L setting. Significantly, the observed mOS for all patients with CPS ≥1 treated with CUE-101 and pembrolizumab of 21.8 months, depicted by the blue line in the graph below, compares favorably to the historical mOS of 12.3 months observed with KEYTRUDA alone. #### Overall Survival of Patients Treated with 4 mg/kg of CUE-101 in Combination with KEYTRUDA In addition to the increased ORR observed in low CPS tumors, we have also observed an enhancement in survival in this population. The 12-month OS rates of 83.9% in patients with low CPS and 100% of patients with high CPS compares favorably with the historical rates observed in the KEYNOTE-048 study, as shown in the table below. #### Overall Survival of CPS High and Low Patients Treated with 4 mg/kg of CUE-101 in Combination with KEYTRUDA #### Data extract:11-Sep-2024 In addition to a significant increase in mOS observed with CUE-101 in combination with KEYTRUDA, we have also observed a mOS of 20.8 months, as depicted by the blue line in the graph below, in the 20 2L+ patients treated with CUE-101 monotherapy at 4 mg/kg as of the September 11, 2024 data cut-off date, which compares favorably to historical third-party mOS data of 8.4 months with KEYTRUDA and 7.5 months with OPDIVO in the 2L setting. #### Data extract:11-Sep-2024 We continue to follow the patients treated in both the CUE-101 Phase 1 monotherapy and combination settings and anticipate providing further updates on the maturing data in the first half of 2025. In January 2024, we met with the Food and Drug Administration, or FDA, in a Type B meeting, which provided clarification and alignment for potential paths forward to registrational trials in both the 2L+ monotherapy and 1L combination settings. In the proposed trial, treatment naïve, front-line patients with HPV+ R/M HNSCC will be randomized to one of three treatment arms: two CUE-101 doses in combination with 200 mg of pembrolizumab or 200mg of pembrolizumab alone, in each case, with dosing to occur every three weeks. ORR will be the primary endpoint with progression free survival, or PFS, and overall survival, or OS, as secondary endpoints. The interim analysis of ORR is anticipated to occur approximately 14 months after the first patient is dosed in this proposed Phase 2 trial, and the primary analysis of ORR is anticipated to occur approximately 22-24 months after the first patient is dosed in this proposed Phase 2 trial. We believe the data resulting from this Phase 2 trial design will provide a robust characterization of treatment effect, confirm the dose to be tested in Phase 3, and increase the overall probability of success for a potential registrational trial of CUE-101, while also providing further risk reduction of the CUE-100 series. Due to the resource requirements of the planned Phase 2 trial, combined with our current prioritization of our autoimmune programs, we are in the process of identifying alternative paths to enable the potential initiation and completion of a Phase 2 trial of CUE-101. ### CUE-102 CUE-102, the second HLA-A02 drug product candidate in clinical development from our CUE-100 series, targets Wilms' tumor 1 protein, or WT1, an oncofetal antigen known to be over-expressed in more than 20 different cancers, including both solid tumors (such as colorectal, gastric, ovarian, pancreatic and lung) and hematologic malignancies (such as acute myeloid leukemia, multiple myeloma and myelodysplastic syndromes). We are currently conducting a Phase 1 monotherapy clinical trial of CUE-102 in late line R/M WT1+ colorectal, gastric, ovarian, and pancreatic cancer. In preclinical experiments in HLA-A2 transgenic mice, we observed that treatment with CUE-102 selectively expanded WT1 specific CD8 T cells within five days post dose, while total CD8 T cell frequencies remained unchanged as seen in panel A below. Treatment with CUE-102 in the HLA-A2 transgenic mice also increased the frequency of WT1 specific CD8 T cells expressing the proliferation marker Ki67 over that observed in total CD8 T cells. Differences in the percentage of Ki67 between WT1 specific CD8 T cells and total CD8 T cells are shown pre- and post-dosing of CUE-102 in panel B below. #### Preclinical Studies of CUE-102 Demonstrated Selective Activation of WT1 Specific CD8 T Cells Selective and robust expansion of WT1 specific T cells has been observed in patients treated in our ongoing CUE-102 monotherapy trial. Consistent with preclinical findings, among the 22 patients tested to date, a trend of increased frequency of WT1 specific T cells is apparent post-dosing with CUE-102, while the frequency of all T cells appears to be unchanged. Expansion of these WT1 tumor specific T cells is expected to enhance anti-tumor immunity with the potential to control disease, drive tumor reductions, and enhance patient survival. The graphs below show reductions in tumor burden that have been observed in two patients treated in the dose-escalation portion of the Phase 1 CUE-102 monotherapy clinical trial. As shown in the graph on the left, a patient with gastric cancer that progressed on three prior lines of therapy, including a checkpoint inhibitor, experienced a decrease in the sum of three target lesions of 34% at week 36, as depicted by the blue line crossing the -30% hash line in green. The graph on the right shows a reduction in tumor burden observed in an ovarian cancer patient as depicted by the blue line intersecting the -30% hash line in green. These patients subsequently experienced progressive disease due to the emergence of new lesions, but importantly, we believe to have provided evidence of the antitumor activity of CUE-102 in the dose escalation portion of the study. #### Reduction of Target Lesions in Patients Treated with CUE-102 Based on these data, we selected CUE-102 4 mg/kg as the expansion dose for Part B, with patients enrolled in all four indications. Patients in all four indications have been treated at the expansion dose and several remain on treatment or in active follow-up. Recently, a pancreatic cancer patient treated with CUE-102 experienced a 40% reduction of tumor burden as shown in the graph below, resulting in an unconfirmed partial response. This patient is currently scheduled for a follow-up scan. #### Pancreatic Cancer Patient Importantly, we have observed a disease control rate of 41% across all late-stage pancreatic cancer patients in the expansion phase of the trial. In addition, pancreatic cancer patients treated with CUE-102 at 2mg/kg and 4mg/kg exhibited a disease control rate of 67%, with two patients surviving for 11 months or greater as of the data cut-off date of September 11, 2024. These pancreatic cancer patients treated with CUE-102 continue to be followed for survival. While we are currently strategically prioritizing our autoimmune programs, we plan to continue to follow the patients treated in the CUE-102 Phase 1 monotherapy setting and anticipate providing further updates on the maturing data in the fourth quarter of 2024. ### Autoimmune Programs In addition to the CUE-100 series, we have leveraged the modularity and versatility of the Immuno-STAT platform to develop additional biologic series outside of oncology, including the CUE-400 and CUE-500 series, which are specifically designed through rational protein engineering to address distinct therapeutic approaches for treating autoimmune disease. The CUE-400 series represents a novel class of bispecific molecules designed to selectively induce and expand regulatory T cells, or Tregs, for chronic autoimmune diseases. The CUE-500 series represents a novel approach to develop selective T cell engagers that can selectively redirect specific memory T cells to deplete autoreactive B cells, which is recognized as an important axis for treatment of autoimmune and inflammatory diseases. We believe preclinical data generated from our evaluation of CUE-401 and the CUE-500 series demonstrates evidence of the desired mechanistic effect of these novel approaches for the treatment of autoimmune disease. ### CUE-401 CUE-401 is a bispecific molecule which has the two key signals, IL-2 and TGF beta, for selective induction of Tregs. The structure of CUE-401 incorporates the same IL-2 variant that is present in CUE-101 and CUE-102. The TGF beta variant was designed to improve the safety profile, enhance manufacturability, and mechanistically align with IL-2 signaling for effective Treg induction and expansion. Co-delivery of IL-2 and TGF beta signals in naïve CD4+ T cells results in the induction of FOX P3 which is the master gene transcription factor for Tregs. The panels below demonstrate Treg induction in human peripheral blood mononuclear cells and exemplify the need for both the IL-2 and TGF beta signals to induce Tregs as neither IL-2 nor TGF beta alone can generate substantial numbers of new Tregs. In contrast, CUE-401, which has both IL-2 and TGF beta, demonstrated the ability to generate a robust population of FOX P3+ Tregs by delivering both required signals as shown below in two different preclinical studies. #### CUE-401 Harnessed Multiple Signals to Induce Tregs in Preclinical Studies We have generated preclinical data in our labs and in collaboration with Dr. Richard DiPaolo of St. Louis University supporting the premise that CUE-401 can potentially expand and induce Tregs. The resulting Tregs are functionally suppressive and maintain a stable phenotype, whereby CUE-401 treatment suppressed the proliferation of self-reactive T cells in a mouse model of autoimmune gastritis. The therapeutic potential of CUE-401 has also been observed in a T cell transfer model of autoimmune gastritis, wherein treatment with CUE-401 led to a prolonged suppression of self-reactive T cells and significantly reduced pathological evidence of disease in the stomachs of treated mice. As shown in the figure below, short-term treatment with CUE-401 resulted in long-term protection from autoimmune gastritis and tissue destruction in a preclinical animal model. The representative histopathology, as shown on the left side, and the compiled gastritis scores, as shown on the right side, demonstrated significant protection from tissue destruction in animals treated with CUE-401. #### Short-term Treatment with CUE-401 Resulted in Significant Long-Term Protection from Gastritis and Tissue Destruction CUE-401 is being developed in strategic collaboration with Ono wherein Ono is supporting all of our ongoing preclinical work to identify a lead clinical candidate. We anticipate selecting a clinical candidate and initiating IND-enabling studies for CUE-401 in the first half of 2025. ### CUE-500 Series The CUE-500 series focuses on autoimmune diseases that are mediated by autoreactive or pathogenic immune cells. CUE-500 series Immuno-STATs are designed to selectively harness our existing protective anti-viral T cell repertoire (virus-specific T cells, or VSTs) and re-direct them to target and deplete pathogenic immune cells, such as B cells. We believe that our approach to deploy a biologic to selectively re-direct “killer” T cells, while avoiding the systemic activation of all T cells, will stimulate T cell-mediated B cell depletion with similarities to what has been exemplified with CD19-CAR-T cell therapy approaches in autoimmunity. We believe that addressing this important mechanism of autoimmune diseases with off-the-shelf biologics will offer significant advantages over cell therapy-based approaches, as well as non-selective pan T cell engagers. The CUE-500 series builds upon the de-risking accomplished with the CUE-100 series and leverages the same molecular scaffold, further supporting the premise that each CUE-100 series Immuno-STAT molecule further de-risks and potentially accelerates subsequent drug product candidates. Our lead CUE-500 series candidate, CUE-501, is a bispecific engineered to selectively redirect existing memory T cells to deplete B cells to address autoimmune and inflammatory diseases. As shown in the left figure below, CUE-501 consists of a bivalent peptide-HLA complex on an Fc backbone, just as utilized in CUE-101 and CUE-102. CUE-501 also contains a single chain variable fragment, or scFv, that binds to the B cell surface antigen CD19 and does not require the presence of the IL-2 variant, due to protective anti-viral T cells being in an activated state. As shown in the graph on the right below, CUE-501 is designed to selectively redirect cytomegalovirus-specific, or CMV-specific, memory T cells to deplete B cells to the same extent achieved with an anti-CD3/CD19 bispecific pan T cell engager. Importantly in this preclinical study, a control CUE-500 molecule that instead targets HIV-specific T cells was unable to mediate B cell killing in this assay, confirming the antigen-specific nature of this mechanism whereby CUE-501 only stimulated a subset of all T cells. #### CUE-501 Selectively redirects CMV-specific memory CD8+ T cells to kill human B cells The selective T cell activation mediated by CUE-501 in preclinical studies is further demonstrated by the graphs below. Pan T cell engagers, such as an anti-CD3/CD19 bispecific, stimulate all T cells and result in significant production of inflammatory cytokines, which leads to the common toxicity of cytokine release syndrome observed in oncology patients treated with these drugs. In contrast, since CUE-501 only activates a subset of all T cells, far lower production of inflammatory cytokines occurs despite the comparable levels of B cell killing shown above. We believe this result supports the potential for CUE-501 to have an improved safety and tolerability profile in patients relative to pan T cell engagers, while also maintaining the benefits of an off-the-shelf biologic relative to the manufacturing challenges and costs associated with cell therapy approaches. We anticipate providing a CUE-501 program update in the fourth quarter of 2024, with lead candidate selection anticipated to occur in the first quarter of 2025. While CUE-501 is being developed to selectively deplete B cells in autoimmune diseases, we believe the modularity of the Immuno-STAT platform also enables the potential generation of additional molecules in the CUE-500 series in the future that could drive selective depletion of other pathogenic immune cell types. #### CUE-501 redirects CMV specific memory CD8+ T cells to kill human B cells with reduced cytokine production relative to anti-CD3/CD19 bispecific ### Plan of Operation Our protein engineering platform has generated a series of precision biologic candidates that are in the clinical development phase for oncology and preclinical development phase for autoimmune disease. Due to its modularity and versatility, we believe our platform has the potential for delivering a diverse and expanding pipeline of promising drug product candidates addressing multiple medical indications. We intend to optimize the value and probability of commercialization of our Immuno-STAT drug product candidates by utilizing a diverse, strategic approach of partnering certain programs, while retaining control and upside potential of others. Through this balanced approach, we aim to provide our stockholders with near, mid and long-term value creation opportunities protected by our portfolio of patents and intellectual property. Since we are a development-stage company, the majority of our business activities to date have been, and our planned future activities will be, devoted to furthering research and development, as well as business development to foster strategically important alliances for resource enhancement. A fundamental part of our corporate development strategy is to establish strategic partnerships with leading pharmaceutical or biotechnology organizations that will allow us to more fully exploit the potential of our technology platform in the areas of oncology and autoimmune disease such as our collaborations described below under the headings “Collaboration Agreement with LG Chem" and "Collaboration and Option Agreement with Ono." ### Critical Accounting Estimates and Significant Judgments Our management’s discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with generally accepted accounting principles in the United States, or U.S. GAAP. The preparation of our financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of our financial statements, and the reported revenue and expenses during the reported periods. We evaluate these estimates and judgments, including those described below, on an ongoing basis. We base our estimates on historical experience, known trends and events, contractual milestones and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. While our significant accounting policies are more fully described in Note 2 to our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q, we believe that the estimates, assumptions and judgments involved in the accounting policies described in Management’s Discussion and Analysis of Financial Condition and Results of Operations in Item 7 of our 2023 Annual Report have the greatest potential impact on our financial statements, so we consider those estimates, assumptions and judgments to be our critical accounting policies and estimates. There were no material changes to our critical accounting policies and estimates during the nine months ended September 30, 2024. ### Recent Accounting Pronouncements and Adopted Standards A discussion of recent accounting pronouncements is included in Note 2 to our condensed consolidated financial statements in this Quarterly Report on Form 10-Q. ### Significant Contracts and Agreements Related to Research and Development Activities ### Einstein License Agreement On January 14, 2015, we entered into a license agreement, as amended and restated on July 31, 2017, and as amended on October 30, 2018, or the Einstein License, with Albert Einstein College of Medicine, or Einstein, for certain patent rights, or the Patents, relating to our core technology platform for the engineering of biologics to control T cell activity, precision, immune-modulatory drug product candidates, and two supporting technologies that enable the discovery of costimulatory signaling molecules (ligands) and T cell targeting peptides. We hold an exclusive worldwide license, with the right to sublicense, import, make, have made, use, provide, offer to sell, and sell all products, processes and services that use the Patents, including certain technology received from Einstein related thereto, which we refer to as the Licensed Products. Under the Einstein License, we are required to: - Pay royalties and amounts based on a certain percentage of proceeds, as defined in the Einstein License, from sales of Licensed Products and sublicense agreements. - Pay escalating annual maintenance fees, which are non-refundable, but are creditable against the amount due to Einstein for royalties. - Make significant payments based upon the achievement of certain milestones, as defined in the Einstein License. As of September 30, 2024, two of these milestones had been achieved, as we had filed an investigational new drug application, or IND, in 2019, and initiated the investigator sponsored Phase 1b neoadjuvant clinical trial for CUE-101 in 2021. - Incur minimum product development costs per year and meet certain diligence obligations until the first commercial sale of the first Licensed Product. As of September 30, 2024, we were in compliance with our obligations under the Einstein License. The Einstein License expires upon the expiration of the last obligation to make royalty payments to Einstein which may be due with respect to certain Licensed Products, unless terminated earlier under the provisions thereof. The Einstein License includes certain termination provisions that will be triggered if we fail to meet our obligations thereunder. We account for the costs incurred in connection with the Einstein License in accordance with Accounting Standards Codification, or ASC, 730, *Research and Development*. For the three and nine months ended September 30, 2024, we incurred $0.03 million and $0.08 million, respectively, in fees payable to Einstein in relation to this license. For the three and nine months ended September 30, 2023, we did not incur any fees payable to Einstein in relation to this license. Such costs are included in research and development costs in our condensed consolidated statements of operations and comprehensive loss. Pursuant to the Einstein License, we issued to Einstein 671,572 shares of our common stock in connection with the consummation of the initial public offering of our common stock on December 27, 2017. ### Collaboration Agreement with LG Chem Effective November 6, 2018, we entered into a Collaboration, License and Option Agreement, or the LG Chem Collaboration Agreement, with LG Chem Ltd., or LG Chem, related to the development of Immuno-STATs focused in the field of oncology. Pursuant to the LG Chem Collaboration Agreement, we granted LG Chem an exclusive license to develop, manufacture and commercialize our lead product, CUE-101, as well as Immuno-STATs that target T cells against two additional cancer antigens, or the Drug Product Candidates, in Australia, Japan, Republic of Korea, Singapore, Malaysia, Vietnam, Thailand, Philippines, Indonesia, China (including Macau and Hong Kong) and Taiwan, which we refer to collectively as the LG Chem Territory. We retain rights to develop and commercialize all assets included in the LG Chem Collaboration Agreement in the United States and in global markets outside of the LG Chem Territory. Under the LG Chem Collaboration Agreement, we will engineer the selected Immuno-STATs for up to three alleles, which are expected to include the predominant alleles in the LG Chem Territory, thereby enhancing our market reach by providing for greater patient coverage of populations in global markets, while LG Chem will establish a chemistry, manufacturing and controls, or CMC, process for the development and commercialization of selected Drug Product Candidates. In addition, LG Chem has the option to select one additional Immuno-STAT for an oncology target, or an Additional Immuno-STAT, for an exclusive worldwide development and commercialization license. On December 18, 2019, we and LG Chem entered into a global license and collaboration agreement, which was amended on November 5, 2020. We refer to such agreement, as amended, as the Global License and Collaboration Agreement. The Global License and Collaboration Agreement supersedes the provisions of the LG Chem Collaboration Agreement related to LG Chem’s option for an Additional Immuno-STAT, which agreement provided for effectiveness if and when LG Chem exercised its option, other than certain select provisions including the length of the option period and representations, warranties and covenants of the parties. On April 30, 2021, LG Chem’s option pursuant to the Global License and Collaboration Agreement expired. Under the terms of the LG Chem Collaboration Agreement, LG Chem paid us a $5.0 million non-refundable, non-creditable upfront payment and purchased $5.0 million of shares of our common stock at a price per share equal to a 20% premium to the volume weighted-average closing price per share over the 30 trading day period immediately prior to the effective date of the LG Chem Collaboration Agreement. We are also eligible to receive additional aggregate payments of up to $400 million if certain research, development, regulatory and commercial milestones are successfully achieved. On May 16, 2019, we earned a $2.5 million milestone payment for the FDA’s acceptance of the IND for our lead drug product candidate, CUE-101, pursuant to the LG Chem Collaboration Agreement. On December 7, 2020, we earned a $1.25 million milestone payment on the selection of a preclinical candidate pursuant to the LG Chem Collaboration Agreement. On November 23, 2021, we earned a $3.0 million milestone payment for the selection of a Drug Product Candidate. In addition, the LG Chem Collaboration Agreement also provides that LG Chem will pay us tiered single-digit royalties on net sales of commercialized Drug Product Candidates, or Collaboration Products, in the LG Chem Territory on a product-by-product and country-by-country basis, until the later of expiration of patent rights in a country, the expiration of regulatory exclusivity in such country, or ten years after the first commercial sale of a Collaboration Product in such country, subject to certain royalty step-down provisions set forth in the LG Chem Collaboration Agreement. Pursuant to the LG Chem Collaboration Agreement, the parties will share research costs related to Collaboration Products, and LG Chem will provide CMC process development for selected Drug Product Candidates and potentially additional downstream manufacturing capabilities, including clinical and commercial supply for Collaboration Products. In return for performing CMC process development, LG Chem is eligible to receive low-single digit percentage royalty payments on the sales of Collaboration Products sold in all countries outside the LG Chem Territory. For the nine months ended September 30, 2024, we recognized revenue of $0.05 million related to the LG Chem Collaboration Agreement. There was no revenue recognized for the three months ended September 30, 2024 related to the LG Chem Collaboration Agreement. For both the three and nine months ended September 30, 2023 we recognized revenue of $0.2 million. As of September 30, 2024, we had recorded $19.9 million in collaboration revenue related to this agreement since the agreement was entered into. The majority of the research phase of the LG Chem Collaboration Agreement was substantially completed by March 31, 2022. The LG Chem Collaboration Agreement includes various representations, warranties, covenants, indemnities and other customary provisions. LG Chem may terminate the LG Chem Collaboration Agreement for convenience or change of control of us on a program-by-program, product-by-product or country-by-country basis, or in its entirety, at any time following the notice period set forth in the LG Chem Collaboration Agreement. Either party may terminate the LG Chem Collaboration Agreement, in its entirety or on a program-by-program, product-by-product or country-by-country basis, in the event of an uncured material breach. The LG Chem Collaboration Agreement is also terminable by either party (i) upon the bankruptcy, insolvency or liquidation of the other party or (ii) for certain activities involving the challenge of certain patents controlled by the other party. Unless earlier terminated, the LG Chem Collaboration Agreement will expire on a product-by-product and country-by-country basis upon the expiration of the applicable royalty term. To date, LG Chem has selected one additional cancer antigen, WT1, which is the focus of the CUE-102 research program. We are currently developing two Collaboration Products with LG Chem pursuant to this agreement. ### Collaboration and Option Agreement with Ono On February 22, 2023, we entered into a strategic collaboration agreement, or the Ono Collaboration and Option Agreement, with Ono Pharmaceutical Co., Ltd., or Ono, to further develop CUE-401 and provide dedicated resources and capabilities to help advance CUE-401 toward the clinic. Under the terms of the Ono Collaboration and Option Agreement, Ono paid us an upfront payment and agreed to fully fund all research activities related to CUE-401 through a specified option period. During this option period, we will be responsible for the research and development of CUE-401. Upon Ono’s exercise of its option to license CUE-401, we will receive an option exercise payment and be eligible for development and commercial milestone payments up to an aggregate of $220 million, as well as tiered royalties on sales. Upon any such exercise, Ono will receive worldwide rights to develop and commercialize CUE-401, with us retaining a 50% co-development and co-commercialization right in the United States. Our decision to elect the co-development and co-commercialization option may be made within 30 days of Ono’s option exercise to license CUE-401. The amount paid by Ono to us for the option exercise and future milestone payments will vary based upon our decision to exercise the co-development and co-commercialization option. Under the terms of the Ono Collaboration and Option Agreement, we will perform research activities related to CUE-401 through a specified option period of 24 months, or the Research Term. During this Research Term, we will be responsible for the execution of scientific investigation, nonclinical, preclinical, and clinical drug research and development activities designed to progress CUE-401 toward a potential IND and regulatory approval, collectively referred to as R&D. Ono is responsible for the funding of R&D activities performed by us. Per the Ono Collaboration and Option Agreement, as consideration for the R&D activities performed by us, Ono (i) has made a one-time, non-refundable, non-creditable upfront payment of $3.0 million to us in March 2023, and (ii) will reimburse us for all costs incurred in conducting research, including (a) pass through costs from third party contractors and (b) full time employee salaries capped at $2.1 million in the first 18 months of the Research Term. Subsequently, the Company and Ono agreed to increase this cap for full time employee salaries to $2.8 million. The term of the Ono Collaboration and Option Agreement extends until the expiration of the Research Term which cannot exceed a 24-month period. We have forecasted that we will be able to complete the R&D activities within this time period. Aside from the $3.0 million upfront payment and funding related to pass through costs, we do not believe that any variable consideration should be included in the transaction price as of September 30, 2024. Such assessment considered the application of the constraint to ensure that estimates of variable consideration would be included in the transaction price only to the extent we have a high degree of confidence that revenue would not be reversed in a subsequent reporting period. We will re-evaluate the transaction price, including the estimated variable consideration included in the transaction price and all constrained amounts, in each reporting period and as other changes in circumstances occur. For the three months ended September 30, 2024 and 2023, we recognized revenue of $3.4 million and $1.9 million, respectively, related to the Ono Collaboration and Option Agreement. For the nine months ended September 30, 2024 and 2023, we recognized revenue of $7.7 million and $3.4 million, respectively, related to the Ono Collaboration and Option Agreement. We recorded short-term research and development liabilities on our balance sheet dated September 30, 2024 of $0.3 million. We also reduced our accounts receivable by $0.5 million for amounts billed to Ono in excess of amounts incurred. As of December 31, 2023, we recorded short-term research and development liabilities of $2.1 million on our consolidated balance sheet. ### Components of Results of Operations ### Collaboration Revenue We have not yet generated commercial revenue from product sales. To date, we have generated revenue from collaboration agreements with Merck Sharp & Dohme Corp. (which terminated in December 2022), LG Chem, and Ono. Collaboration revenue may vary from period to period depending on the progress of our work in connection with our collaboration agreements. ### Operating Expenses We generally recognize operating expenses as they are incurred in two general categories, general and administrative expenses and research and development expenses. Our operating expenses also include non-cash components related to depreciation and amortization of property and equipment and stock-based compensation, which are allocated, as appropriate, to general and administrative expenses and research and development expenses. General and administrative expenses consist of salaries and related expenses for executive, legal, finance, human resources, information technology and administrative personnel, as well as professional fees, insurance costs, and other general corporate expenses. We expect general and administrative expenses to remain consistent in future periods as we continue to incur expenses related to our operation as a public company which requires our compliance with certain regulatory and legal procedures. Research and development expenses consist primarily of compensation expenses, fees paid to consultants, outside service providers and organizations (including research institutes at universities), facility expenses, and development and clinical trial expenses with respect to our drug product candidates. We charge research and development expenses to operations as they are incurred. We expect that our research and development expenses will remain consistent in future periods based on our strategic re-prioritization of our autoimmune programs and organizational restructuring which was announced in July 2024. ### Interest Income We earn interest income from cash invested in money market funds. ### Results of Operations ### Three and Nine Months Ended September 30, 2024 and 2023 Our condensed consolidated statements of operations and comprehensive loss for the three and nine months ended September 30, 2024 and 2023, as discussed herein, are presented below in thousands. | | Three Months Ended September 30, 2024 | 2023 | Nine Months Ended September 30, 2024 | 2023 | | --- | ---: | ---: | ---: | ---: | | **Collaboration revenue** | $3,336 | $2,100 | $7,711 | $3,669 | | **Operating expenses:** | | | | | | General and administrative | 2,867 | 3,645 | 10,564 | 12,071 | | Research and development | 9,381 | 9,874 | 29,111 | 29,915 | | Gain on fixed asset disposal | (97) | — | (97) | — | | Total operating expenses | 12,151 | 13,519 | 39,578 | 41,986 | | **Loss from operations** | (8,815) | (11,419) | (31,867) | (38,317) | | **Other income (expense):** | | | | | | Interest income | 343 | 700 | 1,332 | 1,756 | | Interest expense | (188) | (286) | (643) | (738) | | Total other income, net | 155 | 414 | 689 | 1,018 | | **Net loss** | $(8,660) | $(11,005) | $(31,178) | $(37,299) | ### Collaboration Revenue Collaboration revenue increased by $1.2 million to $3.3 million for the three months ended September 30, 2024, from $2.1 million for the three months ended September 30, 2023. The increase was due to revenue earned from the Ono Collaboration and Option Agreement, which was executed in February 2023. Collaboration revenue increased by $4.0 million to $7.7 million for the nine months ended September 30, 2024, from $3.7 million for the nine months ended September 30, 2023. The increase was due to revenue earned from the Ono Collaboration and Option Agreement, which was executed in February 2023. ### General and Administrative Expenses General and administrative expenses decreased by $0.7 million to $2.9 million for the three months ended September 30, 2024, from $3.6 million for the three months ended September 30, 2023. The decrease was primarily due to a decrease in employee compensation, which includes stock-based compensation. General and administrative expenses decreased by $1.5 million to $10.6 million for the nine months ended September 30, 2024, from $12.1 million for the nine months ended September 30, 2023. The decrease was primarily due to a decrease in employee compensation, which includes stock-based compensation. ### Research and Development Expenses Research and development expenses decreased by $0.5 million to $9.4 million for the three months ended September 30, 2024, from $9.9 million for the three months ended September 30, 2023. The decrease was primarily due to lower clinical trial costs, and employee compensation, which includes stock-based compensation, partially offset by an increase in drug substance manufacturing costs related to CUE-401. Research and development expenses decreased by $0.8 million to $29.1 million for the nine months ended September 30, 2024, from $29.9 million for the nine months ended September 30, 2023. The decrease was primarily due to lower clinical trial costs, and employee compensation, which includes stock-based compensation, partially offset by an increase in professional outside services related to CUE-401. ### Gain on Fixed Asset Disposal Gain on fixed asset disposal was $0.1 million for the three and nine months ended September 30, 2024 . This gain was related to the sale of lab equipment. ### Interest Income Interest income decreased by $0.4 million to $0.3 million for the three months ended September 30, 2024, from $0.7 million for the three months ended September 30, 2023. The decrease was due to lower interest earned on cash and cash equivalents. Interest income decreased by $0.5 million to $1.3 million for the nine months ended September 30, 2024, from $1.8 million for the nine months ended September 30, 2023. The decrease was due to lower interest earned on cash and cash equivalents. ### Interest Expense Interest expense decreased by $0.1 million to $0.2 million for the three months ended September 30, 2024, from $0.3 million for the three months ended September 30, 2023. The decrease was due to a decrease in interest related to the proceeds from borrowings under our Loan and Security Agreement, as amended, or the Loan Agreement, with Silicon Valley Bank, a division of First-Citizens Bank & Trust Company. Interest expense decreased by $0.1 million to $0.6 million for the nine months ended September 30, 2024, from $0.7 million for the nine months ended September 30, 2023. The decrease was due to a decrease in interest related to the proceeds from borrowings under the Loan Agreement with Silicon Valley Bank, a division of First-Citizens Bank & Trust Company. ### Liquidity and Capital Resources We have financed our working capital requirements primarily through private and public offerings of equity securities, cash received from Merck Sharp & Dohme Corp., LG Chem, and Ono under the respective collaboration agreements and borrowings under the Loan Agreement. At September 30, 2024, we had cash and cash equivalents totaling $32.4 million available to fund our ongoing business activities. Additional information concerning our financial condition and results of operations is provided in the financial statements included in this Quarterly Report on Form 10-Q. The amounts that we actually spend for any specific purpose may vary significantly and will depend on a number of factors, including, but not limited to, our research and development activities and programs, clinical testing, regulatory approval, market conditions, and changes in or revisions to our business strategy and technology development plans. On May 9, 2023, we filed a registration statement on Form S-3, which was declared effective on May 26, 2023 (File No. 333-271786), to register for sale from time to time up to $300 million of our common stock, preferred stock, debt securities, warrants, subscription rights and/or units in one or more offerings. In October 2021, we entered into an open market sale agreement, or the October 2021 ATM Agreement, with Jefferies LLC, or Jefferies, as agent, to sell shares of our common stock for aggregate gross proceeds of up to $80 million, from time to time, through an at-the-market equity offering program. The October 2021 ATM Agreement will terminate upon the earliest of (a) the sale of $80 million of shares of our common stock pursuant to the October 2021 ATM Agreement or (b) the termination of the October 2021 ATM Agreement by us or Jefferies. We did not sell any shares during the three months ended September 30, 2024 under the October 2021 ATM Agreement. During the three months ended September 30, 2023, we sold 1,378,867 shares of common stock under the October 2021 ATM Agreement, for proceeds of $5.6 million, net of commission paid, but excluding transaction expenses. During the nine months ended September 30, 2024 and September 30, 2023, we sold 1,428,200 and 1,915,131 shares, respectively, of common stock under the October 2021 ATM Agreement, for proceeds of $3.4 million and $7.6 million, respectively, net of commission paid, but excluding transaction expenses. As of September 30, 2024, we sold an aggregate of 9,028,573 shares of common stock under the October 2021 ATM Agreement for proceeds of $40.4 million, net of commission paid, but excluding transaction expenses, since its inception. On February 15, 2022, we entered into the Loan Agreement, pursuant to which we have borrowed $10.0 million. The Loan Agreement was amended in April 2023 and October 2024. The term loans under the Loan Agreement, or the Term Loans, bear interest at a floating rate per annum equal to the greater of (A) the prime rate (as published in the money rates section of The Wall Street Journal) plus 2.25% and (B) 5.50%. On the first calendar day of each month, we will be required to make monthly interest payments and commencing on June 30, 2023, we began repayment of the Term Loans in (i) 30 consecutive installments of principal plus monthly payments of accrued interest if the additional term loans are not advanced and (ii) 24 months if the additional term loans are advanced. All outstanding principal and accrued and unpaid interest under the Term Loans and all other outstanding obligations with respect to the Term Loans are due and payable in full on December 1, 2025. The Loan Agreement permits voluntary prepayment of all, but not less than all, of the Term Loans, subject to a prepayment premium except if the facility is refinanced with another First Citizens Bank facility. Such prepayment premium would be 1.00% of the principal amount of the Term Loans. Upon prepayment or repayment in full of the Term Loans, we will be required to pay a one-time final payment fee equal to 5.00% of the original principal amount of any funded Term Loans being repaid. The Loan Agreement, as amended, also requires us to have at all times on deposit in our accounts maintained with SVB, unrestricted and unencumbered cash in an amount equal to the lesser of (i) 100% of the dollar value of our consolidated cash, in the aggregate, at all financial institutions and (ii) $20,000,000. On March 10, 2023, Silicon Valley Bank, or SVB, was closed and the Federal Deposit Insurance Company, or FDIC, was appointed receiver for the bank. The FDIC created a successor bridge bank, and all deposits of SVB were transferred to the bridge bank under a systemic risk exception approved by the U.S. Department of the Treasury, the Federal Reserve and the FDIC. On March 27, 2023, First Citizens Bank assumed all of SVB’s deposits and certain other liabilities and acquired substantially all of SVB’s loans and certain other assets from the FDIC. First Citizens Bank continues to hold our Term Loans under the same existing terms and covenants which were in place with SVB. On November 14, 2022, we entered into securities purchase agreements with accredited investors pursuant to which, on November 16, 2022, we issued and sold to such investors in a private placement an aggregate of 7,656,966 shares of common stock and, in lieu of shares of common stock to certain investors, pre-funded warrants, or the 2022 Pre-Funded Warrants, to purchase an aggregate of 1,531,440 shares of common stock, and, in each case, accompanying warrants, or the 2022 Common Stock Warrants, to purchase an aggregate of up to 9,188,406 additional shares of common stock (or 2022 Pre-Funded Warrants in lieu thereof) at a price of $3.265 per share and accompanying 2022 Common Stock Warrant (or $3.2649 per 2022 Pre-Funded Warrant and accompanying 2022 Common Stock Warrant), or the PIPE Financing. The exercise price of the 2022 Common Stock Warrants is $3.93 per share, or if exercised for a 2022 Pre-Funded Warrant in lieu thereof, $3.9299 per 2022 Pre-Funded Warrant. The 2022 Common Stock Warrants are exercisable at any time after they are issued and ending on the fifth anniversary of the closing. The 2022 Pre-Funded Warrants are exercisable at any time after they are issued and will not expire. We received aggregate gross proceeds from the PIPE Financing of $30 million, before deducting placement agent fees and offering expenses of $2.6 million. Piper Sandler & Co. acted as lead placement agent and Public Ventures LLC acted as co-placement agent for the PIPE Financing. On September 26, 2024, we entered into an underwriting agreement, or the Underwriting Agreement, with Oppenheimer & Co. Inc., as representative of the several underwriters named therein, or, collectively, the Underwriters, relating to an underwritten public offering of (i) 11,564,401 shares, or the Shares, of our common stock, $0.001 par value per share, and accompanying common stock warrants (“Common Stock Warrants”) to purchase 2,891,100 shares of our common stock, and (ii) to certain investors in lieu of common stock, pre-funded warrants, or the Pre-Funded Warrants, to purchase 12,435,599 shares of our common stock and accompanying Common Stock Warrants to purchase 3,108,900 shares of common stock. All of the Shares, the Pre-Funded Warrants and the Common Stock Warrants were sold by us. Each Share was offered and sold together with an accompanying Common Stock Warrant at a combined offering price of $0.50, and each Pre-Funded Warrant was offered and sold together with an accompanying Common Stock Warrant at a combined offering price of $0.499, which is equal to the combined offering price per share of common stock and accompanying Common Stock Warrant less the $0.001 exercise price of each Pre-Funded Warrant. The Underwriters purchased (i) each Share and accompanying Common Stock Warrant from us pursuant to the Underwriting Agreement at a combined price of $0.47 and (ii) each Pre-Funded Warrant and accompanying Common Stock Warrant from us pursuant to the Underwriting Agreement at a combined price of $0.46906. We recorded net proceeds from the offering of $10.8 million, after deducting underwriting discounts and commissions and offering expenses of $1.1 million, and excluding any proceeds that may be received from exercise of the Common Stock Warrants and the Pre-Funded Warrants. If we issue additional equity securities to raise funds, the ownership percentage of our existing stockholders would be reduced. New investors may demand rights, preferences or privileges senior to those of existing holders of our common stock. If we issue debt securities, we may be required to grant security interests in our assets, could have substantial debt service obligations, and lenders may have a senior position (compared to stockholders) in any potential future bankruptcy or liquidation. Additionally, corporate collaboration and licensing arrangements may require us to incur non-recurring and other charges, give up certain rights relating to our intellectual property and research and development activities, increase our near and long-term expenditures, issue securities that dilute our existing stockholders, issue debt which may require liens on our assets and which will increase our monthly expense obligations, or disrupt our management and business. ### Cash Flows Based on our current plans and forecasted expenses, we believe that our existing cash and cash equivalents, as of September 30, 2024, will enable us to fund our operations into the fourth quarter of 2025. However, we will need to raise additional capital to fund our future operations and remain as a going concern. We expect to finance our future cash needs through a combination of equity offerings, collaborations, and other strategic alliances. Volatility in capital markets and general economic conditions in the United States may be a significant obstacle to raising the required funds and, as a result, we may be unable to secure the necessary funding on acceptable terms. This raises substantial doubt about our ability to continue as a going concern. The following table summarizes our changes in cash, cash equivalents, and restricted cash for the nine months ended September 30, 2024 and 2023: *(in thousands)* | Net cash provided by (used in): | Nine Months Ended September 30, 2024 | 2023 | | --- | ---: | ---: | | Operating activities | $(27,301) | $(29,003) | | Investing activities | 33 | 25,002 | | Financing activities | 11,175 | 7,078 | | Net change in cash, cash equivalents, and restricted cash | $(16,093) | $3,077 | ### Operating Activities Net cash used in operating activities totaled $27.3 million for the nine months ended September 30, 2024 compared to $29.0 million for the nine months ended September 30, 2023. The decrease of $1.7 million was primarily due to a decrease in research and development contract liabilities and accrued expenses, partially offset by increases in accounts payable. ### Investing Activities Net cash provided by investing activities totaled less than $0.03 million for the nine months ended September 30, 2024 compared to net cash provided by investing activities of $25.0 million during the nine months ended September 30, 2023. The decrease of $25.0 million in cash provided was due to redemptions of marketable securities during the nine months ended September 30, 2023. ### Financing Activities Net cash provided by financing activities totaled $11.2 million for the nine months ended September 30, 2024 compared to $7.1 million for the nine months ended September 30, 2023. The increase of $4.1 million was due to net proceeds received from our September 2024 offering. ### Funding Requirements We expect our expenses to increase in connection with our ongoing activities, particularly as we continue the research and development of our Immuno-STAT platform and continue ongoing and initiate new clinical trials of, and seek marketing approval for, our drug product candidates. In addition, we expect to incur additional costs associated with operating as a public company. Our expenses will also increase if, and as, we: - continue the clinical development of our CUE-100 series, including CUE-101 and CUE-102, which we have currently decided to deprioritize; - continue the preclinical development of CUE-401 and CUE-501; - leverage our programs, including our autoimmune programs, to advance our other drug product candidates into preclinical and clinical development; - seek regulatory approvals for any drug product candidates for which we successfully complete clinical trials; - seek to discover and develop additional drug product candidates; - establish a sales, marketing, medical affairs and distribution infrastructure to commercialize any drug product candidates for which we may obtain marketing approval and intend to commercialize on our own or jointly; - hire additional clinical, quality control and scientific personnel; - expand our manufacturing, quality, operational, financial and management systems; - increase personnel, including personnel to support our clinical development, manufacturing and commercialization efforts and our operations as a public company; - maintain, expand and protect our intellectual property portfolio; - acquire or in-license other drug product candidates and technologies; and - incur additional legal, accounting and other expenses in operating as a public company. In July 2024, we determined to strategically prioritize our autoimmune programs, including CUE-401 and CUE-501, and completed an organizational restructuring to strengthen operational efficiencies, including an approximate 25% reduction in our workforce. We discussed in Note 1 of the notes to the condensed consolidated financial statements under Accounting Standards Update, or ASU, 2014-15, Presentation of Financial Statements—Going Concern (Subtopic 205-40), or, ASC 205-40, we have the responsibility to evaluate whether conditions or events raise substantial doubt about our ability to meet our future financial obligations as they become due within one year after the date the financial statements are issued. Under ASC 205-40, this evaluation initially cannot take into consideration the potential mitigating effects of plans that have not been fully implemented as of the date the financial statements are issued. Since we currently believe that our existing cash and cash equivalents, as of September 30, 2024, and our current operating plan will enable us to fund our operations into the fourth quarter of 2025, we have determined that this cash runway of less than 12 months from the date of issuance of our financial statements included in this Quarterly Report on Form 10-Q, along with our accumulated deficit, history of losses, and future expected losses meet the ASC 205-40 standard for raising substantial doubt about our ability to continue as a going concern within one year of the issuance date of our financial statements included in this Quarterly Report on Form 10-Q. While we have plans in place to mitigate this risk, which primarily consist of raising additional capital through a combination of equity offerings, collaborations, and other strategic alliances, and, depending on the availability and level of additional financings, cash expenditure reduction, there is no guarantee that we will be successful in these mitigation efforts. We will need to raise additional capital or incur additional indebtedness to continue to fund our operations in the future. Our ability to raise additional funds will depend on financial, economic and market conditions, many of which are outside of our control, and we may be unable to raise financing when needed, or on terms favorable to us. If we are unable to raise additional funds when needed, we may be required to delay, reduce or eliminate our product development or future commercialization efforts, or grant rights to develop and market drug product candidates that we would otherwise prefer to develop and market ourselves, which could adversely affect our business prospects, and we may be unable to continue our operations. Because of numerous risks and uncertainties associated with the research, development and commercialization of our drug product candidates, we are unable to estimate the exact amount of our working capital requirements. Factors that may affect our planned future capital requirements and accelerate our need for additional working capital include the following: - the progress, timing, scope and costs of our clinical trials, including the ability to timely enroll patients in our ongoing, planned and potential future clinical trials; - our ability to secure third party support through partnerships and collaborations to further develop the CUE-100 series programs, including CUE-101 and CUE-102; - the outcome, timing and cost of regulatory approvals by the FDA and other comparable regulatory authorities, including the potential that the FDA or other comparable regulatory authorities may require that we perform more studies than those that we currently expect; - the number and characteristics of drug product candidates that we may in-license and develop; - our ability to successfully commercialize our drug product candidates, if approved; - the amount of sales and other revenues from drug product candidates that we may commercialize, if any, including the selling prices for such potential products and the availability of adequate third-party reimbursement; - selling and marketing costs associated with our potential products, including the cost and timing of expanding our marketing and sales capabilities; - the terms and timing of any potential future collaborations, licensing or other arrangements that we may establish; - cash requirements of any future acquisitions and/or the development of other drug product candidates; - the costs of operating as a public company; - the cost and timing of completion of commercial-scale, outsourced manufacturing activities; - the time and cost necessary to respond to technological and market developments; - any disputes which may occur between us and our employees, collaborators, including Einstein, LG Chem and Ono, or other prospective business partners; and - the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights. A change in the outcome of any of these or other variables with respect to the development of any of our drug product candidates could significantly change the costs and timing associated with the development of that drug product candidate. Further, our operating plans may change in the future, and we may need additional funds to meet operational needs and capital requirements associated with such operating plans. Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of public or private equity offerings, debt financings, collaborations, strategic partnerships or marketing, distribution or licensing arrangements with third parties and grants from organizations and foundations. If we raise additional funds by selling shares of our common stock or other equity-linked securities, the ownership interest of our current stockholders will be diluted. We may seek to access the public or private capital markets whenever conditions are favorable, even if we do not have an immediate need for additional capital at that time. If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams or drug product candidates or to grant licenses on terms that may not be acceptable to us. If we raise additional funds through debt financing, we may have to grant a security interest on our assets to the future lenders, our debt service costs may be substantial, and the lenders may have a preferential position in connection with any future bankruptcy or liquidation. If we are unable to raise additional capital when needed, we may be required to curtail the development of our technology or materially curtail or reduce our operations. We could be forced to sell or dispose of our rights or assets. Any inability to raise adequate funds on commercially reasonable terms could have a material adverse effect on our business, results of operation and financial condition, including the possibility that a lack of funds could cause our business to fail, dissolve and liquidate with little or no return to investors. ### Principal Commitments During the three and nine months ended September 30, 2024, there were no material changes to our contractual obligations and commitments as of December 31, 2023 as described in Management’s Discussion and Analysis of Financial Condition and Results of Operations in Item 7 of our 2023 Annual Report. ## Controls and procedures As filed, 3,374 characters. ### Disclosure Controls and Procedures We are responsible for maintaining disclosure controls and procedures, as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934, or the Exchange Act. Disclosure controls and procedures are controls and other procedures designed to ensure that the information required to be disclosed by us in the reports that we file or submit under the Exchange Act is recorded, processed, summarized, and reported within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by us in the reports that we file or submit under the Exchange Act is accumulated and communicated to our management, including our principal executive officer and our principal financial officer, as appropriate to allow timely decisions regarding required disclosure. Based on our management’s evaluation (with the participation of our principal executive officer and our principal financial officer) of our disclosure controls and procedures as required by Rule 13a-15 under the Exchange Act, our principal executive officer and our principal financial officer have concluded that our disclosure controls and procedures were effective as of September 30, 2024, the end of the period covered by this report. ### Inherent Limitations on Effectiveness of Controls Our management, including our principal executive officer and our principal financial officer, do not expect that our disclosure controls or our internal control over financial reporting will prevent or detect all errors and all fraud. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the control system’s objectives will be met. The design of a control system must reflect the fact that there are resource constraints, and the benefits of controls must be considered relative to their costs. Further, because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that misstatements due to error or fraud will not occur or that all control issues and instances of fraud, if any, have been detected. These inherent limitations include the realities that judgments in decision-making can be faulty and that breakdowns can occur because of a simple error or mistake. Controls can also be circumvented by the individual acts of some persons, by collusion of two or more people, or by management override of the controls. The design of any system of controls is based in part on certain assumptions about the likelihood of future events, and there can be no assurance that any design will succeed in achieving its stated goals under all potential future conditions. Projections of any evaluation of control effectiveness to future periods are subject to risks. Over time, controls may become inadequate because of changes in conditions or deterioration in the degree of compliance with policies or procedures. ### Changes in Internal Control over Financial Reporting There were no changes in our internal control over financial reporting during the three months ended September 30, 2024 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting. ## Risk factors As filed, 5,131 characters. We operate in a rapidly changing environment that involves a number of risks that could materially affect our business, financial condition or future results, some of which are beyond our control. The occurrence of any of these risks could harm our business, financial condition, results of operations and/or growth prospects or cause our actual results to differ materially from those contained in forward-looking statements we have made in this report and those we may make from time to time. In evaluating us and our business, you should carefully consider the following risks, the information included in this Quarterly Report on Form 10-Q and in other documents we file with the SEC and the risk factors previously disclosed in “Part I, Item 1A. Risk Factors” of our 2023 Annual Report. ***If we fail to comply with the continued listing requirements of Nasdaq, our common stock may be delisted and the price of our common stock and our ability to access the capital markets could be negatively impacted.*** We are required to comply with the continued listing requirements of the Nasdaq Stock Market LLC, or Nasdaq, including, among other things, maintaining a minimum closing bid price of at least $1.00 per share, or shares of our common stock may be subject to delisting, which would have a material adverse effect on our business. Any potential delisting of our common stock could have a material adverse effect on the market for, and liquidity and price of, our common stock and would adversely affect our ability to raise capital on terms acceptable to us, or at all. Delisting from Nasdaq could also have other negative results, including, without limitation, the potential loss of confidence by investors, customers and employees and fewer business development opportunities. Any delisting of our common stock from Nasdaq would also make it more difficult for our stockholders to sell their shares of our common stock in the public market. On August 15, 2024, we received a deficiency letter from Nasdaq indicating that we failed to comply with the minimum bid price requirement. Subsequently, on October 18, 2024, we received a letter from Nasdaq notifying us that we had regained compliance with the minimum bid price requirement and were in compliance with the listing requirements. Our common stock will continue to be listed and traded on the Nasdaq Capital Market. However, there can be no assurance that we will be able to continue to comply with the Nasdaq listing requirements. ***We have a loan agreement that requires us to meet certain operating covenants and place restrictions on our operating and financial flexibility.*** On February 15, 2022, we entered into the Loan Agreement with SVB, as amended in April 2023, which has been assumed by First Citizens Bank, pursuant to which we have borrowed $10.0 million. The outstanding principal amount under the Loan Agreement as of September 30, 2024 is $5.0 million. The Loan Agreement is secured by substantially all of our properties, rights and assets, except for our intellectual property, which is subject to a negative pledge, and certain other customary exclusions. Because of the security interest, First Citizens Bank’s rights to repayment from a liquidation of the assets subject to that security interest would be senior to the rights of other creditors. The Loan Agreement, as amended, includes customary covenants including covenants requiring us to maintain our corporate existence and governmental approvals, deliver certain financial reports and maintain insurance coverage. As of September 30, 2024, we had unrestricted and unencumbered cash and cash equivalents totaling $32.4 million. Additionally, we are restricted in our ability to transfer collateral, incur additional indebtedness, engage in mergers or acquisitions, pay dividends or make other distributions, make investments, create liens, sell assets and agree to a change in control. Upon the occurrence of an event of default, which includes our failure to satisfy our payment obligations under the Loan Agreement, the breach of certain of these covenants under the Loan Agreement such as the covenant to maintain unrestricted and unencumbered cash in an amount equal to the lesser of (i) $20,000,000 and (ii) 100% of the dollar value of our consolidated cash, or the occurrence of a material adverse change in our business, First Citizens Bank is entitled to accelerate amounts due under the Loan Agreement and dispose the collateral as permitted under applicable law. Any declaration by First Citizens Bank of an event of default and its exercise of its remedies in the event of such declaration of an event of default, such as acceleration of the amounts due under the Loan Agreement, would adversely impact the amount of cash we have available to fund our operations, could significantly harm our business and prospects, and could cause the price of our common stock to decline. For a further description of the Loan Agreement, please refer to Notes 5 and 13 of the Notes to Condensed Consolidated Financial Statements included in this Quarterly Report on Form 10-Q. Filed Nov 14, 2024. Source: SEC EDGAR, the filing index for accession 0000950170-24-127005. Last ingested by Listed: Oct 24, 2026, 15:14 ET. No prices; not investment advice.