Financial Data and Key Metrics Changes - The company reported collaboration revenue of approximately $68,000 for Q3 2022, down from $2.4 million in Q3 2021 [35] - Research and development expenses decreased to $7.6 million in Q3 2022 from $11.3 million in Q3 2021, primarily due to reductions in laboratory and drug manufacturing costs [35] - General and administrative expenses also decreased to $3.5 million in Q3 2022 from $4.1 million in Q3 2021, attributed to lower stock-based compensation and consulting fees [35] - The company ended the quarter with approximately $59.1 million in cash and cash equivalents, along with $51.5 million in working capital [36] Business Line Data and Key Metrics Changes - The CUE-101 monotherapy trial demonstrated single-agent antitumor efficacy in recurrent head and neck squamous cell carcinoma, with a median overall survival benefit emerging from the survival follow-up [19] - CUE-101 showed well-behaved pharmacokinetics with low interpatient variability at the recommended Phase II dose of 4 mg/kg, maintaining exposure throughout multiple treatment cycles [20] Market Data and Key Metrics Changes - The company is focused on the HPV-positive head and neck cancer market, where CUE-101 is positioned to provide a significant clinical benefit compared to existing treatments [61] - The combination of CUE-101 with pembrolizumab has shown a 40% objective response rate, which is significantly higher than the 19% response rate observed with pembrolizumab monotherapy [26] Company Strategy and Development Direction - The company aims to leverage the clinical validation of CUE-101 to expand its Immuno-STAT platform, targeting various cancers with a modular approach [33] - The recent IND approval for CUE-102, which targets Wilms Tumor 1, underscores the strategic advantages gained from the derisking accomplished by CUE-101 [33] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the breakthrough potential of the Immuno-STAT platform, emphasizing the transformative nature of their approach to cancer therapy [38] - The company plans to define a potential registration trial for CUE-101 by mid-next year, based on the strength of emerging data [39] Other Important Information - The company has entered into a securities purchase agreement for $30 million in private investment, which will support the development of its Immuno-STAT platform through 2024 [36] - The CUE-102 trial is actively enrolling patients across 15 sites in the U.S., with plans to present additional data at upcoming medical meetings [32] Q&A Session Summary Question: Can you discuss typical treatments seen post-progression in the combination study? - Management indicated that they are collecting data but cannot provide specifics on subsequent therapies due to the variability across multiple sites [45] Question: Do you have a median duration of response for either the monotherapy or combination study? - Management has not calculated the median duration of response yet, as it is too early for the combination study [46] Question: Can you provide updates on the neoadjuvant study and patient enrollment? - The neoadjuvant study has treated close to 10 patients, with preliminary data showing increases in NK cells and tumor-infiltrating lymphocytes [47] Question: What is the duration of response for the best responding combo patient? - The duration of response in monotherapy is reported as 42 weeks, with indications of increased progression-free survival in the combination therapy [51] Question: How do you envision advancing NeoStat versus swapping in different allelic variants? - The company is pursuing both strategies, leveraging strong confidence in targeting tumor epitopes while optimizing processes for clinical application [52] Question: What is the expected median overall survival for monotherapy in the third line? - A median overall survival of 12 months is anticipated, which would represent a significant clinical benefit compared to existing treatments [61] Question: What opportunities do you see for CUE-102 now that CUE-101 has derisked the platform? - CUE-102 targets a wide range of cancers, and early activity in the dose escalation phase will serve as a catalyst for further validation and expansion into additional indications [64][65]

PART I. FINANCIAL INFORMATION [Item 1. Financial Statements](index=6&type=section&id=Item%201.%20Financial%20Statements) This section presents the unaudited consolidated financial statements, including the balance sheets, statements of operations and comprehensive loss, statements of stockholders' equity, and statements of cash flows, along with detailed notes explaining the company's accounting policies, financial instruments, and significant agreements [Consolidated Balance Sheets](index=6&type=section&id=Consolidated%20Balance%20Sheets) Consolidated Balance Sheets Data | Metric | Sep 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | | :-------------------------- | :-------------------------- | :-------------------------- | | Cash and cash equivalents | $29,726 | $64,371 | | Marketable securities | $29,457 | — | | Total current assets | $61,700 | $68,469 | | Total assets | $76,300 | $83,401 | | Total current liabilities | $10,222 | $12,788 | | Total liabilities | $25,536 | $17,909 | | Total stockholders' equity | $50,764 | $65,492 | [Consolidated Statements of Operations and Other Comprehensive Loss](index=7&type=section&id=Consolidated%20Statements%20of%20Operations%20and%20Other%20Comprehensive%20Loss) Consolidated Statements of Operations and Other Comprehensive Loss Data | Metric | Three Months Ended Sep 30, 2022 (in thousands) | Three Months Ended Sep 30, 2021 (in thousands) | Nine Months Ended Sep 30, 2022 (in thousands) | Nine Months Ended Sep 30, 2021 (in thousands) | | :----------------------------------- | :--------------------------------------------- | :--------------------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Collaboration revenue | $68 | $2,395 | $1,094 | $6,687 | | General and administrative expenses | $3,528 | $4,125 | $12,465 | $12,660 | | Research and development expenses | $7,571 | $11,288 | $27,246 | $29,846 | | Total operating expenses | $11,099 | $15,413 | $39,453 | $42,506 | | Net loss | $(10,955) | $(12,993) | $(38,418) | $(35,777) | | Net loss per common share (basic & diluted) | $(0.31) | $(0.41) | $(1.11) | $(1.16) | [Consolidated Statements of Stockholders' Equity](index=8&type=section&id=Consolidated%20Statements%20of%20Stockholders%27%20Equity) Consolidated Statements of Stockholders' Equity Data | Metric | Sep 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | | :----------------------------------- | :-------------------------- | :-------------------------- | | Common stock | $35 | $32 | | Additional paid in capital | $286,685 | $262,906 | | Accumulated other comprehensive loss | $(92) | — | | Accumulated deficit | $(235,864) | $(197,446) | | Total stockholders' equity | $50,764 | $65,492 | - Issuance of common stock from ATM offering, net of sales agent commission and fees, contributed **$16,598,000** to additional paid-in capital for the nine months ended **September 30, 2022**[34](index=34&type=chunk) - Stock-based compensation for the nine months ended **September 30, 2022**, was **$7,384,000**[34](index=34&type=chunk) [Consolidated Statements of Cash Flows](index=9&type=section&id=Consolidated%20Statements%20of%20Cash%20Flows) Consolidated Statements of Cash Flows Data | Cash Flow Activity | Nine Months Ended Sep 30, 2022 (in thousands) | Nine Months Ended Sep 30, 2021 (in thousands) | | :---------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Net cash used in operating activities | $(31,292) | $(28,192) | | Net cash (used in) provided by investing activities | $(29,609) | $9,108 | | Net cash provided by financing activities | $26,256 | $11,851 | | Net decrease in cash, cash equivalents, and restricted cash | $(34,645) | $(7,233) | | Cash, cash equivalents, and restricted cash at end of period | $29,876 | $67,783 | [Notes to the Consolidated Financial Statements](index=10&type=section&id=Notes%20to%20the%20Consolidated%20Financial%20Statements) [Note 1. Organization and Basis of Presentation](index=10&type=section&id=Note%201.%20Organization%20and%20Basis%20of%20Presentation) The company, incorporated in Delaware in 2014, is a clinical-stage biopharmaceutical company focused on developing novel injectable biologics for cancer, infectious diseases, and autoimmune diseases. It has incurred recurring losses and negative cash flows since inception, with current cash and marketable securities of $59.183 million as of September 30, 2022, believed to be sufficient for the next twelve months, but additional capital will be needed for long-term viability - Cue Biopharma is a clinical-stage biopharmaceutical company developing novel injectable biologics designed to selectively engage and modulate tumor-specific T cells within the body to treat a broad range of cancers, chronic infectious diseases, and autoimmune diseases[40](index=40&type=chunk) - The company has incurred recurring losses and negative cash flows from operations since inception[41](index=41&type=chunk) Cash, Cash Equivalents, and Marketable Securities | Metric | Sep 30, 2022 (in thousands) | | :-------------------------------------- | :-------------------------- | | Cash, cash equivalents, and marketable securities | $59,183 | - Management believes that current cash, cash equivalents, and marketable securities on hand at **September 30, 2022**, are sufficient to fund operations for at least the next **twelve months**, but future viability depends on raising additional capital[41](index=41&type=chunk) [Note 2. Summary of Significant Accounting Policies](index=10&type=section&id=Note%202.%20Summary%20of%20Significant%20Accounting%20Policies) This note outlines the significant accounting policies used in preparing the unaudited consolidated financial statements, including the basis of presentation, consolidation, use of estimates, impact of the COVID-19 pandemic, and policies for cash, marketable securities, property and equipment, revenue recognition, and stock-based compensation - The accompanying unaudited consolidated financial statements have been prepared in accordance with SEC rules and U.S. GAAP, reflecting all necessary adjustments for a fair statement[42](index=42&type=chunk) - The preparation of financial statements requires management to make estimates and assumptions, particularly related to collaboration revenue, potential liabilities, stock-based compensation, deferred tax assets, and long-lived assets[49](index=49&type=chunk) - The COVID-19 pandemic may continue to impact the company's business and financial results due to evolving factors like macroeconomic conditions, capital markets access, and supply chain disruptions[50](index=50&type=chunk)[51](index=51&type=chunk) - Cash equivalents are highly liquid investments with maturities of **three months** or less; marketable securities have maturities greater than **ninety days** and less than **one year**, classified as available-for-sale and recorded at fair value[53](index=53&type=chunk)[54](index=54&type=chunk) - Collaboration revenue is recognized under ASC 606, with variable consideration estimated using the 'most likely amount' method, and patent costs are charged to general and administrative expense as incurred[62](index=62&type=chunk)[68](index=68&type=chunk) [Note 3. Fair Value](index=15&type=section&id=Note%203.%20Fair%20Value) This note details the company's fair value measurements for financial assets and liabilities, categorizing them into a three-level hierarchy based on input observability. As of September 30, 2022, cash equivalents and marketable securities were valued using Level 1 and Level 2 inputs, respectively - The fair value hierarchy prioritizes inputs to valuation techniques into three levels: Level 1 (quoted prices in active markets), Level 2 (observable inputs other than quoted prices), and Level 3 (unobservable inputs)[85](index=85&type=chunk)[86](index=86&type=chunk)[87](index=87&type=chunk) Fair Value Measurements | Asset | Sep 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | Fair Value Level | | :---------------------- | :-------------------------- | :-------------------------- | :--------------- | | Cash equivalents | $23,256 | $52,509 | Level 1 | | Marketable securities | $29,457 | — | Level 2 | | Total | $52,713 | $52,509 | | - The carrying values of accounts receivable, prepaid expenses, other current assets, accounts payable, and accrued expenses approximate their fair value due to their short-term nature[97](index=97&type=chunk) [Note 4. Marketable Securities](index=16&type=section&id=Note%204.%20Marketable%20Securities) As of September 30, 2022, the company held $29.457 million in marketable securities, primarily U.S. Treasury securities, which were not present at December 31, 2021, and recorded an unrealized loss of $92,000 Marketable Securities Summary | Metric | Sep 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | | :--------------------------- | :-------------------------- | :-------------------------- | | Amortized Cost | $29,550 | — | | Gross Unrealized Gains | — | — | | Gross Unrealized Losses | $(92) | — | | Fair Value | $29,457 | — | - Marketable securities consist of U.S. Treasury securities[98](index=98&type=chunk) [Note 5. Property and Equipment](index=17&type=section&id=Note%205.%20Property%20and%20Equipment) This note details the composition and net value of property and equipment, which decreased from $2.112 million at December 31, 2021, to $1.642 million at September 30, 2022, primarily due to depreciation and a loss on the sale of fixed assets Property and Equipment Details | Asset | Sep 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | | :-------------------------- | :-------------------------- | :-------------------------- | | Laboratory equipment | $5,253 | $5,203 | | Furniture and fixtures | $81 | $93 | | Computer and office equipment | $302 | $253 | | Leasehold improvements | $60 | $7 | | Less accumulated depreciation | $(4,054) | $(3,444) | | Net property and equipment | $1,642 | $2,112 | - Depreciation expense for the nine months ended **September 30, 2022**, was approximately **$630,000**[100](index=100&type=chunk) - The company recorded a loss on the sale of fixed assets of **$4,300** during the nine months ended **September 30, 2022**[100](index=100&type=chunk) [Note 6. Loan with Silicon Valley Bank](index=17&type=section&id=Note%206.%20Loan%20with%20Silicon%20Valley%20Bank) The company entered into a $20 million term loan agreement with Silicon Valley Bank on February 15, 2022, drawing $10 million initially. The loan bears a floating interest rate (prime + 2.25% or 5.50%, whichever is greater) and is secured by most company assets, excluding intellectual property - On **February 15, 2022**, the company entered into a Loan and Security Agreement with Silicon Valley Bank for up to **$20,000,000** in term loans, drawing **$10,000,000** on the closing date[101](index=101&type=chunk) - The Term Loans bear interest at a floating rate per annum equal to the greater of (A) the prime rate plus **2.25%** and (B) **5.50%**. At **September 30, 2022**, the interest rate was **8.5%**[101](index=101&type=chunk) - The Term Loans are secured by substantially all of the company's properties, rights, and assets, except for its intellectual property[101](index=101&type=chunk) Interest Expense Related to Term Loans | Metric | Nine Months Ended Sep 30, 2022 (in thousands) | | :----------------------------------- | :-------------------------------------------- | | Interest expense related to Term Loans | $354 | | Interest expense related to accretion of final payment | $76 | [Note 7. Stock-Based Compensation](index=18&type=section&id=Note%207.%20Stock-Based%20Compensation) This note details stock option and restricted stock unit (RSU) activity, including valuation assumptions and compensation expenses. For the nine months ended September 30, 2022, stock-based compensation expense totaled $7.384 million, with $13.856 million in unrecognized expense remaining Stock Option Valuation Assumptions | Assumption | 2022 | 2021 | | :------------------------ | :------------------- | :------------------- | | Risk-free interest rate | 1.53% - 2.92% | 0.61% - 1.31% | | Expected dividend yield | 0% | 0% | | Expected volatility | 92.1% - 95.7% | 97.8% - 100.9% | | Expected life | 5.50 to 6.25 years | 5.50 to 6.25 years | Stock-Based Compensation Expense | Category | Three Months Ended Sep 30, 2022 (in thousands) | Nine Months Ended Sep 30, 2022 (in thousands) | | :--------------------------- | :--------------------------------------------- | :-------------------------------------------- | | General and administrative | $1,003 | $3,650 | | Research and development | $1,061 | $3,734 | | Total | $2,064 | $7,384 | - As of **September 30, 2022**, total unrecognized stock-based compensation expense was approximately **$13,856,000**, expected to be recognized over a weighted average remaining period of **2.13 years**[107](index=107&type=chunk) [Note 8. Warrants](index=20&type=section&id=Note%208.%20Warrants) As of September 30, 2022, the company had 789,358 common stock warrants outstanding from a December 2017 issuance, with an exercise price of $9.38 per share, expiring on December 26, 2022. Another tranche of warrants expired in June 2022 Outstanding Warrants | Tranche | Dec 31, 2021 | Sep 30, 2022 | | :------------------------------------ | :----------- | :----------- | | Warrant Issued June 15, 2015- Tranche 1 | 62,611 | 0 | | Warrant Issued December 27, 2017- Tranche 2 | 789,358 | 789,358 | | Total | 851,969 | 789,358 | - The remaining outstanding warrants (Tranche 2) have an exercise price of **$9.38 per share** and expire on **December 26, 2022**[116](index=116&type=chunk) [Note 9. Collaboration Revenue](index=21&type=section&id=Note%209.%20Collaboration%20Revenue) The company recognizes collaboration revenue under ASC 606 from license and R&D services, primarily from agreements with Merck and LG Chem. Revenue decreased significantly in 2022 due to the expiration of the Merck agreement and completion of the research phase with LG Chem - The company recognizes collaboration revenue under ASC 606, typically including promises related to licenses to intellectual property and research and development services[120](index=120&type=chunk) - The research collaboration term under the Merck Collaboration Agreement expired on **December 31, 2021**, and the research phase under the LG Chem collaboration was substantially complete on **March 31, 2022**[129](index=129&type=chunk)[134](index=134&type=chunk) Collaboration Revenue by Partner | Collaboration | Three Months Ended Sep 30, 2022 (in thousands) | Three Months Ended Sep 30, 2021 (in thousands) | Nine Months Ended Sep 30, 2022 (in thousands) | Nine Months Ended Sep 30, 2021 (in thousands) | | :------------ | :--------------------------------------------- | :--------------------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Merck | $0 | $293 | $0 | $1,762 | | LG Chem | $68 | $2,102 | $1,094 | $4,925 | | Total | $68 | $2,395 | $1,094 | $6,687 | - To date, the company has not recognized any development, regulatory or commercial milestones or royalty revenue resulting from any of its collaboration arrangements[122](index=122&type=chunk) [Note 10. Commitments and Contingencies](index=24&type=section&id=Note%2010.%20Commitments%20and%20Contingencies) The company's primary commitments include the Einstein License Agreement, requiring potential milestone payments up to $1.85 million per product/indication and $5.75 million for cumulative sales. There are no accruals for contingent liabilities, and no material legal proceedings are ongoing - The Einstein License Agreement requires the company to make significant payments based upon the achievement of certain milestones[137](index=137&type=chunk) - Aggregate milestone payments under the Einstein License Agreement could reach up to **$1.85 million** for each product/indication and up to **$5.75 million** for cumulative sales of all Licensed Products[137](index=137&type=chunk) - As of **September 30, 2022**, the company was not a party to any legal proceedings or threatened legal proceedings that would have a material adverse effect on its business[141](index=141&type=chunk) [Note 11. Leases](index=24&type=section&id=Note%2011.%20Leases) The company accounts for leases under ASC 842, recording right-of-use assets and corresponding lease liabilities. It terminated its Cambridge office/lab lease in April 2022, recording a $258,000 gain, and relocated its headquarters to new premises in Boston, incurring new lease liabilities - The company accounts for leases under ASC 842, which requires recording a right-of-use asset and a corresponding lease liability for most lease arrangements[142](index=142&type=chunk) - The Laboratory and Office Lease in Cambridge, Massachusetts, was terminated effective **April 30, 2022**, resulting in a gain on right-of-use asset termination of approximately **$258,000** for the nine months ended **September 30, 2022**[150](index=150&type=chunk) - The company relocated its corporate headquarters to 40 Guest Street, Boston, Massachusetts, under a new License Agreement commencing **April 15, 2022**, with a monthly rental rate of **$200,700** for the first year[150](index=150&type=chunk)[151](index=151&type=chunk) Operating Lease Balances | Metric | Sep 30, 2022 (in thousands) | Dec 31, 2021 (in thousands) | | :-------------------------- | :-------------------------- | :-------------------------- | | Operating lease right-of-use asset | $9,561 | $9,810 | | Current operating lease liability | $3,335 | $4,932 | | Long-term operating lease liability | $6,321 | $5,121 | [Note 12. Subsequent Events](index=27&type=section&id=Note%2012.%20Subsequent%20Events) On November 14, 2022, the company entered into a private placement agreement to issue 7,656,966 shares of common stock and 1,531,440 pre-funded warrants, along with accompanying warrants for up to 9,188,406 additional shares, expecting to raise approximately $30 million in gross proceeds - On **November 14, 2022**, the company entered into securities purchase agreements for a private placement of **7,656,966** shares of common stock and **1,531,440** pre-funded warrants, with accompanying warrants for up to **9,188,406** additional shares[157](index=157&type=chunk) - The private placement is expected to generate aggregate gross proceeds of approximately **$30 million**[220](index=220&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=28&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on the company's financial condition and results of operations, highlighting its strategic focus on oncology programs, clinical trial progress, the impact of the COVID-19 pandemic, and liquidity management, including recent financing activities and future funding requirements [Overview](index=28&type=section&id=Overview) The company is a clinical-stage biopharmaceutical company developing Immuno-STAT™ T cell engager biologics, prioritizing its CUE-100 series for oncology. It aims to selectively modulate tumor-specific T cells to treat cancer while seeking third-party support for non-oncology programs. The company has no commercial revenue and requires additional capital - The company is a clinical-stage biopharmaceutical company developing a novel class of T cell engager biologics, Immuno-STAT™ (Selective Targeting and Alteration of T Cells) platform[160](index=160&type=chunk) - The company is currently prioritizing and strategically focusing on drug product candidates for treating cancer in its CUE-100 series, which exploits rationally engineered interleukin 2 (IL-2)[160](index=160&type=chunk) - The company is actively seeking third-party support through partnerships or alternative funding structures to further develop its programs outside of oncology (CUE-200, CUE-300, and CUE-400 series)[160](index=160&type=chunk) - The company has not yet commenced any commercial revenue-generating operations, has limited cash flows from operations, and will need to access additional capital[160](index=160&type=chunk) [Our Pipeline of Immuno-STAT T Cell Engagers](index=28&type=section&id=Our%20Pipeline%20of%20Immuno-STAT%20T%20Cell%20Engagers) The company is making significant progress with its IL-2-based CUE-100 series for oncology, with CUE-101 showing anti-tumor activity and favorable tolerability in Phase 1 monotherapy and combination trials for HPV+ HNSCC. CUE-102, targeting WT1, has initiated a Phase 1 trial, and new platforms like Neo-STAT™ and RDI-STAT are being developed to expand targeting capabilities - CUE-101, the most advanced clinical stage asset, is currently being dosed in a Phase 1b monotherapy trial for HPV-driven R/M HNSCC and a Phase 1 combination trial with KEYTRUDA®[163](index=163&type=chunk) - CUE-101 as a monotherapy demonstrated a confirmed partial response lasting over **42 weeks** and seven patients with durable stable disease, with an observed increased trend in median overall patient survival approaching greater than **12 months** (**13.3 months**)[163](index=163&type=chunk) - CUE-101 received Fast Track Designation for the treatment of R/M HPV+ HNSCC as a monotherapy and in combination with KEYTRUDA[165](index=165&type=chunk) - In combination with KEYTRUDA, CUE-101 showed an initial overall response rate (ORR) of **40%** in **10** evaluable patients at the RP2D, with two confirmed ongoing PRs and two unconfirmed PRs (later confirmed)[165](index=165&type=chunk) - CUE-102, targeting Wilms' tumor-1 protein (WT1), received IND acceptance in **April 2022** and has initiated a Phase 1 monotherapy dose-escalation trial for WT1-positive recurrent/metastatic gastric, pancreatic, ovarian, and colorectal cancers[169](index=169&type=chunk) - The company is developing Neo-STAT™ (peptide-less HLA molecules for flexible targeting) and RDI-STAT (targeting moiety on Fc fragment to redirect anti-viral T cells to tumors) to address cancer heterogeneity and immune escape mechanisms[169](index=169&type=chunk) [The COVID-19 Pandemic](index=31&type=section&id=The%20COVID-19%20Pandemic) The COVID-19 pandemic has caused supply chain disruptions for lab supplies and delays with contract research organizations (CROs), including a six-week delay in CUE-102 GMP material manufacturing, which pushed back its IND filing - The COVID-19 pandemic has caused supply chain disruptions for lab supplies and delays with contract research organizations (CROs)[170](index=170&type=chunk) - The manufacture of CUE-102 drug product candidate GMP material was delayed by approximately **six weeks** due to the Defense Production Act, impacting its IND filing date[170](index=170&type=chunk) [Plan of Operation](index=31&type=section&id=Plan%20of%20Operation) The company is in the development phase, focusing on R&D to advance its Immuno-STAT platform and drug candidates. Its strategy includes early-stage clinical development, extensive patent protection, and seeking strategic partnerships for later-stage development and commercialization - The majority of the company's business activities are devoted to furthering research and development of its Immuno-STAT platform[172](index=172&type=chunk) - A fundamental part of the corporate development strategy is to establish strategic partnerships with pharmaceutical or biotechnology organizations for more extensive, later stages of clinical development[172](index=172&type=chunk) [Critical Accounting Estimates and Significant Judgments](index=32&type=section&id=Critical%20Accounting%20Estimates%20and%20Significant%20Judgments) The company's financial statements rely on estimates and assumptions, particularly for collaboration revenue, potential liabilities, stock-based compensation, deferred tax assets, and long-lived assets. No material changes to these critical accounting policies occurred during the reported period - The preparation of financial statements requires making estimates and assumptions that affect reported amounts, including collaboration revenue, potential liabilities, stock-based compensation, deferred tax assets, and long-lived assets[173](index=173&type=chunk) - There were no material changes to the company's critical accounting policies and estimates during the **three** and **nine months** ended **September 30, 2022**[174](index=174&type=chunk) [Recent Accounting Pronouncements and Adopted Standards](index=32&type=section&id=Recent%20Accounting%20Pronouncements%20and%20Adopted%20Standards) This section refers to Note 2 of the consolidated financial statements for a discussion of recent accounting pronouncements - A discussion of recent accounting pronouncements is included in Note 2 to the consolidated financial statements[175](index=175&type=chunk) [Significant Contracts and Agreements Related to Research and Development Activities](index=32&type=section&id=Significant%20Contracts%20and%20Agreements%20Related%20to%20Research%20and%20Development%20Activities) The company maintains key agreements, including the Einstein License Agreement for its core technology platform and collaboration agreements with Merck and LG Chem. The Merck agreement expired in 2021, while the LG Chem agreement continues for oncology development in Asia, having generated significant upfront and milestone payments [Einstein License Agreement](index=32&type=section&id=Einstein%20License%20Agreement) The company holds an exclusive worldwide license from Albert Einstein College of Medicine for patent rights related to its core technology platform. It is required to pay royalties, annual maintenance fees, and milestone payments, and was in compliance with its obligations as of September 30, 2022 - The company holds an exclusive worldwide license from Albert Einstein College of Medicine for certain patent rights relating to its core technology platform[176](index=176&type=chunk)[177](index=177&type=chunk) - Obligations under the license include paying royalties, escalating annual maintenance fees, and significant milestone payments upon achievement of certain events[177](index=177&type=chunk) - As of **September 30, 2022**, the company was in compliance with its obligations under the Einstein License[178](index=178&type=chunk) Einstein License Agreement Fees | Period | 2022 (in thousands) | 2021 (in thousands) | | :---------------------------- | :------------------ | :------------------ | | Three months ended Sep 30 | $0 | $80 | | Nine months ended Sep 30 | $0 | $257 | [Collaboration Agreement with Merck](index=33&type=section&id=Collaboration%20Agreement%20with%20Merck) The collaboration agreement with Merck for autoimmune disease indications expired on December 31, 2021. The company received a $2.5 million upfront payment and recognized collaboration revenue from this agreement in prior periods, but none in 2022, as it is now prioritizing oncology programs - The research collaboration term under the Merck Collaboration Agreement for autoimmune disease indications expired on **December 31, 2021**[182](index=182&type=chunk) - Merck paid the company a **$2.5 million** nonrefundable up-front payment[184](index=184&type=chunk) Merck Collaboration Revenue | Period | 2022 (in thousands) | 2021 (in thousands) | | :---------------------------- | :------------------ | :------------------ | | Three months ended Sep 30 | $0 | $293 | | Nine months ended Sep 30 | $0 | $1,762 | [Collaboration Agreement with LG Chem](index=33&type=section&id=Collaboration%20Agreement%20with%20LG%20Chem) The collaboration with LG Chem focuses on oncology Immuno-STATs, granting LG Chem exclusive development and commercialization rights in certain Asian countries. The company received a $5.8 million upfront payment, a $5 million equity investment, and $6.75 million in milestone payments to date. The research phase was substantially complete by March 31, 2022, leading to a decrease in recognized revenue in 2022 - The LG Chem Collaboration Agreement grants LG Chem an exclusive license to develop, manufacture, and commercialize Immuno-STATs focused in oncology in certain Asian countries[186](index=186&type=chunk) - The company received a **$5.8 million** non-refundable upfront payment and a **$5.0 million** equity investment from LG Chem[187](index=187&type=chunk) - The company is eligible to receive up to an additional **$400.0 million** in research, development, regulatory, and commercial milestones, plus tiered single-digit percentage royalties on net sales[187](index=187&type=chunk) - Milestone payments earned to date total **$6.75 million**[134](index=134&type=chunk) LG Chem Collaboration Revenue | Period | 2022 (in thousands) | 2021 (in thousands) | | :---------------------------- | :------------------ | :------------------ | | Three months ended Sep 30 | $68 | $2,102 | | Nine months ended Sep 30 | $1,094 | $4,925 | - The majority of the research phase of the collaboration agreement was substantially complete on **March 31, 2022**[188](index=188&type=chunk) [Results of Operations](index=35&type=section&id=Results%20of%20Operations) The company has not generated commercial revenue, relying on collaboration revenue which significantly decreased in 2022 due to the expiration of the Merck agreement and completion of the LG Chem research phase. Operating expenses, including general & administrative and R&D, also saw reductions - The company has not generated commercial revenue from product sales, with collaboration revenue being its primary source[191](index=191&type=chunk) - Collaboration revenue decreased by approximately **$2,327,000** for the **three months** and **$5,593,000** for the **nine months** ended **September 30, 2022**, compared to the prior year[198](index=198&type=chunk) - The decrease in collaboration revenue is attributed to the expiration of the Merck Collaboration Agreement and the completion of the research phase under the LG Chem collaboration[198](index=198&type=chunk) [Collaboration Revenue](index=35&type=section&id=Collaboration%20Revenue_Results) Collaboration revenue for the three months ended September 30, 2022, was $68,000, a significant decrease from $2,395,000 in the prior year, and for the nine months, it was $1,094,000, down from $6,687,000. This decline is attributed to the expiration of the Merck agreement and the completion of the LG Chem research phase Collaboration Revenue Summary | Period | 2022 (in thousands) | 2021 (in thousands) | Change (2022 vs 2021) (in thousands) | | :---------------------------- | :------------------ | :------------------ | :----------------------------------- | | Three months ended Sep 30 | $68 | $2,395 | $(2,327) | | Nine months ended Sep 30 | $1,094 | $6,687 | $(5,593) | - The decrease was due to the expiration of the research collaboration term under the Merck Collaboration Agreement and the completion of the research phase under the LG Chem collaboration[198](index=198&type=chunk) [General and Administrative](index=36&type=section&id=General%20and%20Administrative_Results) General and administrative expenses decreased by $597,000 for the three months and $195,000 for the nine months ended September 30, 2022, compared to the prior year, mainly due to lower stock-based compensation, professional/consulting fees, and rent General and Administrative Summary | Period | 2022 (in thousands) | 2021 (in thousands) | Change (2022 vs 2021) (in thousands) | | :---------------------------- | :------------------ | :------------------ | :----------------------------------- | | Three months ended Sep 30 | $3,528 | $4,125 | $(597) | | Nine months ended Sep 30 | $12,465 | $12,660 | $(195) | - The decrease for the **three months** was primarily due to lower stock-based compensation, professional and consulting fees, rent expense, and overhead[199](index=199&type=chunk) - The decrease for the **nine months** was primarily due to lower professional and consulting and legal expenses[201](index=201&type=chunk) [Research and Development](index=36&type=section&id=Research%20and%20Development_Results) Research and development expenses decreased by $3.717 million for the three months and $2.600 million for the nine months ended September 30, 2022, compared to the prior year. This reduction was mainly driven by lower laboratory and drug substance manufacturing costs, stock-based compensation, and licensing fees, partially offset by increased clinical trial fees for CUE-101 and CUE-102 Research and Development Summary | Period | 2022 (in thousands) | 2021 (in thousands) | Change (2022 vs 2021) (in thousands) | | :---------------------------- | :------------------ | :------------------ | :----------------------------------- | | Three months ended Sep 30 | $7,571 | $11,288 | $(3,717) | | Nine months ended Sep 30 | $27,246 | $29,846 | $(2,600) | - The decrease was primarily due to lower laboratory and drug substance manufacturing costs, stock-based compensation, other professional fees, and licensing fees[203](index=203&type=chunk)[205](index=205&type=chunk) - The nine-month decrease was offset by increased clinical trial fees related to CUE-101 and CUE-102 trials[205](index=205&type=chunk) [Gain on Right-of-use Asset Termination](index=37&type=section&id=Gain%20on%20Right-of-use%20Asset%20Termination) The company recognized a gain of $258,000 on right-of-use asset termination for the nine months ended September 30, 2022, due to the termination of its Cambridge office and laboratory lease. No such gain was recorded in the prior year Gain on Right-of-use Asset Termination Summary | Period | 2022 (in thousands) | 2021 (in thousands) | Change (2022 vs 2021) (in thousands) | | :---------------------------- | :------------------ | :------------------ | :----------------------------------- | | Three months ended Sep 30 | $0 | $0 | $0 | | Nine months ended Sep 30 | $258 | $0 | $258 | - The gain resulted from the termination of the operating lease agreement for the laboratory and office space in Cambridge, Massachusetts, effective **April 30, 2022**[208](index=208&type=chunk) [Interest Income, net](index=37&type=section&id=Interest%20Income%2C%20net) Interest income significantly increased to $200,000 for the three months and $296,000 for the nine months ended September 30, 2022, compared to $25,000 and $42,000 respectively in 2021, primarily due to higher interest yields on cash and cash equivalents Interest Income, net Summary | Period | 2022 (in thousands) | 2021 (in thousands) | Change (2022 vs 2021) (in thousands) | | :---------------------------- | :------------------ | :------------------ | :----------------------------------- | | Three months ended Sep 30 | $200 | $25 | $175 | | Nine months ended Sep 30 | $296 | $42 | $254 | - The increase was primarily due to higher interest yields on the company's cash and cash equivalents[209](index=209&type=chunk) [Interest Expense, net](index=37&type=section&id=Interest%20Expense%2C%20net) Interest expense increased to $124,000 for the three months and $355,000 for the nine months ended September 30, 2022, from zero in the prior year. This rise is mainly due to interest payments on the Silicon Valley Bank term loan and amortization of debt issuance costs, partially offset by amortization/accretion on investments Interest Expense, net Summary | Period | 2022 (in thousands) | 2021 (in thousands) | Change (2022 vs 2021) (in thousands) | | :---------------------------- | :------------------ | :------------------ | :----------------------------------- | | Three months ended Sep 30 | $124 | $0 | $124 | | Nine months ended Sep 30 | $355 | $0 | $355 | - The increase was primarily due to cash paid for interest expense related to borrowings under the Loan Agreement with Silicon Valley Bank and amortization of deferred issuance costs[210](index=210&type=chunk) [Liquidity and Capital Resources](index=37&type=section&id=Liquidity%20and%20Capital%20Resources) The company's liquidity is primarily from equity offerings, collaboration agreements, and a term loan. As of September 30, 2022, it had $59.183 million in cash, cash equivalents, and marketable securities, expected to fund operations for at least the next 12 months. However, significant additional capital will be required for future R&D and commercialization efforts. A private placement in November 2022 is expected to raise $30 million - The company has financed its working capital requirements primarily through private and public offerings of equity securities, cash from collaboration agreements, and borrowings under the Loan Agreement[211](index=211&type=chunk) Cash, Cash Equivalents, and Marketable Securities | Metric | Sep 30, 2022 (in thousands) | | :-------------------------------------- | :-------------------------- | | Cash, cash equivalents, and marketable securities | $59,183 | - Existing cash, cash equivalents, and marketable securities as of **September 30, 2022**, are expected to fund operating requirements for at least the next **12 months**, but additional capital will be needed for future operations[230](index=230&type=chunk)[231](index=231&type=chunk) - On **November 14, 2022**, the company entered into a private placement expected to receive aggregate gross proceeds of approximately **$30 million**[220](index=220&type=chunk) [Cash Flows](index=39&type=section&id=Cash%20Flows) For the nine months ended September 30, 2022, net cash used in operating activities increased to $31.292 million, investing activities used $29.609 million (compared to providing $9.108 million in 2021), and financing activities provided $26.256 million, leading to a net decrease in cash of $34.645 million Cash Flow Activities Summary | Cash Flow Activity | Nine Months Ended Sep 30, 2022 (in thousands) | Nine Months Ended Sep 30, 2021 (in thousands) | | :---------------------------------- | :-------------------------------------------- | :-------------------------------------------- | | Operating activities | $(31,292) | $(28,192) | | Investing activities | $(29,609) | $9,108 | | Financing activities | $26,256 | $11,851 | | Net decrease in cash | $(34,645) | $(7,233) | [Operating Activities](index=39&type=section&id=Operating%20Activities) Cash used in operating activities increased to $31.292 million for the nine months ended September 30, 2022, primarily due to a net loss of $38.418 million and decreases in various liabilities, partially offset by non-cash adjustments like stock-based compensation and depreciation - Net cash used in operating activities was **$31,292,000** for the nine months ended **September 30, 2022**[224](index=224&type=chunk) - Cash used was primarily due to a net loss of **$38,418,000** and decreases in accrued expenses, research and development contract liability, accounts payable, and operating lease liability[224](index=224&type=chunk) - Partially offset by increases in stock-based compensation (**$7,384,000**) and depreciation and amortization (**$719,000**)[224](index=224&type=chunk) [Investing Activities](index=39&type=section&id=Investing%20Activities) Investing activities used $29.609 million in cash for the nine months ended September 30, 2022, a significant shift from providing $9.108 million in 2021. This change was mainly driven by the purchase of $29.5 million in short-term marketable securities - Net cash used in investing activities was **$29,609,000** for the nine months ended **September 30, 2022**, compared to **$9,108,000** provided in the prior year[225](index=225&type=chunk) - The decrease of **$38,717,000** in cash from investing activities was primarily due to the purchase of **$29,500,000** in short-term investments in marketable securities[225](index=225&type=chunk) [Financing Activities](index=39&type=section&id=Financing%20Activities) Financing activities provided $26.256 million in cash for the nine months ended September 30, 2022, an increase from $11.851 million in 2021. This was primarily due to $16.598 million from ATM equity offerings and $10 million from term loan borrowings - Net cash provided by financing activities was **$26,256,000** for the nine months ended **September 30, 2022**, an increase of **$14,405,000** from the prior year[226](index=226&type=chunk) - Cash from financing activities included **$16,598,000** from the sale of common stock via ATM offering and **$10,000,000** from borrowings under the Loan Agreement[226](index=226&type=chunk) [Funding Requirements](index=39&type=section&id=Funding%20Requirements) The company anticipates increased expenses for R&D, clinical trials, regulatory approvals, and public company operations. It has prioritized oncology programs and taken steps to reduce costs. While existing cash is expected to last 12 months, significant additional capital will be needed, potentially through equity offerings, debt, or partnerships, with risks of dilution or asset relinquishment - The company expects expenses to increase due to ongoing R&D, clinical trials, regulatory approvals, and operating as a public company[227](index=227&type=chunk)[228](index=228&type=chunk) - The company has prioritized its oncology programs (CUE-100 series) and is actively seeking third-party support for non-oncology programs (CUE-200, CUE-300, CUE-400 series)[229](index=229&type=chunk) - Existing cash, cash equivalents, and marketable securities as of **September 30, 2022**, are expected to fund operating requirements for at least the next **12 months**[230](index=230&type=chunk) - Additional capital will be needed, potentially through public or private equity offerings, debt financings, collaborations, or grants, which could lead to ownership dilution or relinquishing valuable rights[231](index=231&type=chunk)[234](index=234&type=chunk) [Principal Commitments](index=41&type=section&id=Principal%20Commitments) There were no material changes to the company's contractual obligations and commitments during the three and nine months ended September 30, 2022, other than entering into a new headquarters lease - No material changes to contractual obligations and commitments occurred during the **three** and **nine months** ended **September 30, 2022**, other than entering into a new headquarters lease[236](index=236&type=chunk) [ITEM 3. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK](index=42&type=section&id=ITEM%203.%20QUANTITATIVE%20AND%20QUALITATIVE%20DISCLOSURES%20ABOUT%20MARKET%20RISK) As a smaller reporting company, the registrant is not required to provide quantitative and qualitative disclosures about market risk - As a smaller reporting company, the registrant is not required to provide the information required by this Item 3[238](index=238&type=chunk) [ITEM 4. CONTROLS AND PROCEDURES](index=42&type=section&id=ITEM%204.%20CONTROLS%20AND%20PROCEDURES) Management, including the CEO and CFO, concluded that the company's disclosure controls and procedures were effective as of September 30, 2022. They acknowledge inherent limitations in control systems and reported no material changes in internal control over financial reporting during the quarter - The principal executive officer and principal financial officer concluded that the company's disclosure controls and procedures were effective as of **September 30, 2022**[239](index=239&type=chunk) - Management acknowledges that control systems have inherent limitations and can provide only reasonable, not absolute, assurance that objectives will be met[240](index=240&type=chunk) - There were no changes in internal control over financial reporting during the **three months** ended **September 30, 2022**, that materially affected or are reasonably likely to materially affect internal control over financial reporting[241](index=241&type=chunk) [Disclosure Controls and Procedures](index=42&type=section&id=Disclosure%20Controls%20and%20Procedures) The company's disclosure controls and procedures were evaluated and deemed effective as of September 30, 2022, ensuring timely and accurate reporting of information required by the Exchange Act - Disclosure controls and procedures are designed to ensure that information required to be disclosed in SEC reports is recorded, processed, summarized, and reported within specified time periods[239](index=239&type=chunk) - The principal executive officer and principal financial officer concluded that disclosure controls and procedures were effective as of **September 30, 2022**[239](index=239&type=chunk) [Inherent Limitations on Effectiveness of Controls](index=42&type=section&id=Inherent%20Limitations%20on%20Effectiveness%20of%20Controls) Management recognizes that control systems have inherent limitations, providing only reasonable assurance against errors or fraud, as they can be circumvented by individual acts, collusion, or management override - Management does not expect that disclosure controls or internal control over financial reporting will prevent or detect all errors and all fraud[240](index=240&type=chunk) - A control system can provide only reasonable, not absolute, assurance, and can be circumvented by individual acts, collusion, or management override[240](index=240&type=chunk) [Changes in Internal Control over Financial Reporting](index=42&type=section&id=Changes%20in%20Internal%20Control%20over%20Financial%20Reporting) No changes in internal control over financial reporting occurred during the three months ended September 30, 2022, that materially affected or are reasonably likely to materially affect the company's internal control over financial reporting - There were no changes in internal control over financial reporting during the **three months** ended **September 30, 2022**, that have materially affected, or are reasonably likely to materially affect, the company's internal control over financial reporting[241](index=241&type=chunk) PART II. OTHER INFORMATION [ITEM 1. LEGAL PROCEEDINGS](index=43&type=section&id=ITEM%201.%20LEGAL%20PROCEEDINGS) The company is not currently a party to any material legal proceedings - The company is not currently a party to any material legal proceedings[242](index=242&type=chunk) [ITEM 1A. RISK FACTORS](index=43&type=section&id=ITEM%201A.%20RISK%20FACTORS) Investors should carefully consider the risks outlined in this report and the company's 2021 Annual Report, as these factors could materially affect the business, financial condition, results of operations, and future growth prospects - Investment in the company's securities involves risk, and investors should carefully consider the summary of principal risks in this report and the risk factors detailed in Item 1A of the **2021** Annual Report[11](index=11&type=chunk)[243](index=243&type=chunk) - If any of the risks occur, the company's business, financial condition, results of operations, and future growth prospects could be materially and adversely affected[12](index=12&type=chunk) [ITEM 2. UNREGISTERED SALES OF EQUITY SECURITIES AND USE OF PROCEEDS](index=43&type=section&id=ITEM%202.%20UNREGISTERED%20SALES%20OF%20EQUITY%20SECURITIES%20AND%20USE%20OF%20PROCEEDS) No unregistered sales of equity securities or use of proceeds to report for this period - No unregistered sales of equity securities and use of proceeds to report[244](index=244&type=chunk) [ITEM 3. DEFAULTS UPON SENIOR SECURITIES](index=43&type=section&id=ITEM%203.%20DEFAULTS%20UPON%20SENIOR%20SECURITIES) No defaults upon senior securities to report for this period - No defaults upon senior securities to report[245](index=245&type=chunk) [ITEM 4. MINE SAFETY DISCLOSURES](index=43&type=section&id=ITEM%204.%20MINE%20SAFETY%20DISCLOSURES) This item is not applicable to the company - Mine Safety Disclosures are not applicable[246](index=246&type=chunk) [ITEM 5. OTHER INFORMATION](index=43&type=section&id=ITEM%205.%20OTHER%20INFORMATION) No other information to report for this period - No other information to report[247](index=247&type=chunk) [ITEM 6. EXHIBITS](index=44&type=section&id=ITEM%206.%20EXHIBITS) This section lists the exhibits filed with the Form 10-Q, including termination agreements, rider to license agreement, certifications, and XBRL documents - Exhibits include a Termination of License Agreement, a Rider to License Agreement, Certifications (pursuant to Rule 13a-14(a) or Rule 15d-14(a) of the Securities Exchange Act of 1934 and 18 U.S.C. Section 1350), and Inline eXtensible Business Reporting Language (XBRL) documents[249](index=249&type=chunk)

Cue Biopharma, Inc. (NASDAQ:CUE) Q2 2022 Earnings Conference Call August 23, 2022 4:30 PM ET Company Participants Dan Passeri - Chief Executive Officer Anish Suri - President & Chief Scientific Officer Ken Pienta - Acting Chief Medical Officer Matteo Levisetti - SVP, Clinical Development Kerri Millar - Chief Financial Officer Conference Call Participants Stephen Willey - Stifel Reni Benjamin - JMP Securities Mark Breidenbach - Oppenheimer Operator Greetings and welcome to the Cue Biopharma Update Call. At t ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED JUNE 30, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO Commission file number: 001-38327 Cue Biopharma, Inc. (Exact name of registrant as specified in its charter) Delaware 47-3324577 (State or other jurisdictio ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED MARCH 31, 2022 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO Commission file number: 001-38327 Cue Biopharma, Inc. (Exact name of registrant as specified in its charter) Delaware 47-3324577 (State or other jurisdicti ...

PART I [Item 1. Business](index=3&type=section&id=Item%201.%20Business) Cue Biopharma is a clinical-stage biopharmaceutical company focused on engineering novel injectable biologics using its Immuno-STAT™ platform to selectively modulate T cells, prioritizing oncology programs and seeking partnerships for non-oncology programs, with no commercial revenue and a need for additional capital - Cue Biopharma is a clinical-stage biopharmaceutical company developing novel injectable biologics via its Immuno-STAT™ platform to selectively engage and modulate targeted T cells[17](index=17&type=chunk)[485](index=485&type=chunk) - The company is currently prioritizing its oncology programs, specifically the IL-2 based CUE-100 series, and is actively seeking third-party support for its non-oncology programs (CUE-200, CUE-300, CUE-400 series)[18](index=18&type=chunk)[20](index=20&type=chunk)[486](index=486&type=chunk) - As of the report date, the company has not commenced any commercial revenue-generating operations and has limited cash flows, indicating a need for additional capital[19](index=19&type=chunk)[487](index=487&type=chunk) [Overview](index=5&type=section&id=Overview) The company is a clinical-stage biopharmaceutical firm utilizing its proprietary Immuno-STAT™ platform to develop injectable biologics for selective T cell modulation, aiming to treat cancer, chronic infectious diseases, and autoimmune conditions while minimizing broad immune activation, with current strategic focus on the CUE-100 oncology series and other programs seeking external support - The Immuno-STAT™ platform is designed to selectively engage and modulate targeted T cells directly within the patient's body, aiming to fight cancer and restore health while avoiding deleterious side effects of broad immune activation[17](index=17&type=chunk) - Current strategic priority is on drug product candidates for treating cancer in the CUE-100 series, which utilizes rationally engineered interleukin 2 (IL-2) within the Immuno-STAT framework[18](index=18&type=chunk) - Programs outside of oncology (CUE-200, CUE-300, CUE-400 series) are actively seeking third-party support through partnerships, collaborations, or alternative funding structures[18](index=18&type=chunk) [Our Immuno-STAT Platform Pipeline](index=5&type=section&id=Our%20Immuno-STAT%20Platform%20Pipeline) The company's pipeline prioritizes the IL-2-based CUE-100 series for oncology, with CUE-101 being the most advanced clinical asset in Phase 1b monotherapy and Phase 1 combination trials for HPV-driven head and neck cancer, while other candidates include CUE-102 (targeting WT1) with an IND filing anticipated by Q1 2022, and CUE-103 (targeting KRAS G12V), with the Neo-STAT™ platform being developed for broader targeting flexibility - CUE-101, the most advanced clinical stage asset, is currently in a Phase 1b monotherapy trial and a first-line Phase 1 combination trial with KEYTRUDA® (pembrolizumab) for HPV-driven recurrent/metastatic head and neck cancer (R/M HNSCC)[21](index=21&type=chunk)[22](index=22&type=chunk)[23](index=23&type=chunk) - CUE-102, targeting Wilm's tumor protein (WT1) over-expressed in over 20 different cancers, is anticipated to have an Investigational New Drug (IND) application filed by the end of the first quarter of 2022[26](index=26&type=chunk)[68](index=68&type=chunk) - The Neo-STAT™ platform is a derivative scaffold designed to provide greater flexibility for targeting multiple tumor epitopes, enhancing production efficiencies, and potentially enabling personalized neo-antigen strategies[28](index=28&type=chunk)[75](index=75&type=chunk) [Our Business Strategy](index=7&type=section&id=Our%20Business%20Strategy) The company's core strategy is to become a leader in highly selective biologics for immune modulation, involving advancing the IL-2-based CUE-100 oncology series through clinical trials to demonstrate selective T cell activation and anti-tumor immunity, while also seeking strategic partnerships for its non-oncology programs (CUE-200, CUE-300, CUE-400 series) - Primary objective is to become a leading biopharmaceutical company developing breakthrough, highly selective and differentiated biologics for safe and effective therapeutic immune modulation[32](index=32&type=chunk) - Key strategies include advancing the IL-2-based CUE-100 series for oncology to demonstrate selective and tolerable IL-2 delivery to tumor-specific T cells and expanding patient access[32](index=32&type=chunk) - Actively seeking strategic partnerships and collaborations or alternative funding structures for programs outside of oncology, including the CUE-200, CUE-300, and CUE-400 series[33](index=33&type=chunk) [Our Approach](index=7&type=section&id=Our%20Approach) The Immuno-STAT platform is designed to mimic the natural immune synapse by combining key T cell activation signals (Signal 1: peptide-MHC complex, Signal 2: co-stimulatory signals like IL-2) into a single, stable molecular scaffold, aiming for selective T cell modulation, avoiding broad immune activation, and built on an Fc backbone for stability and manufacturability - The Immuno-STAT platform's core protein framework combines key T cell activation signals (Signal 1: stabilized peptide-MHC complex, Signal 2: activating co-stimulatory signals like modified IL-2) into a singular molecular scaffold[38](index=38&type=chunk)[39](index=39&type=chunk)[41](index=41&type=chunk)[43](index=43&type=chunk) - This design allows for selective delivery of activating signals to tumor-specific T cells, circumventing global immune activation and enabling therapeutic dosing of highly immune-activating signals such as IL-2[39](index=39&type=chunk)[44](index=44&type=chunk) - Immuno-STAT molecules are manufactured using established processes similar to antibody and Fc-fusion molecules, providing modularity and structural stability via an Fc backbone[39](index=39&type=chunk)[43](index=43&type=chunk) [The Immuno-STAT: "Immune Responses, on Cue"](index=9&type=section&id=The%20Immuno-STAT%3A%20%22Immune%20Responses%2C%20on%20Cue%22) The Immuno-STAT platform develops biologic drug candidates that selectively modulate antigen-specific T cells by fusing a TCR targeting pMHC complex (Signal 1) with co-stimulatory signaling molecules (Signal 2), mimicking natural immune responses, aiming to overcome challenges of systemic, non-specific immune activation and the complexities of adoptive cell therapies, offering 'off-the-shelf' biologics with targeted action and convenient administration - Immuno-STATs are designed to emulate natural immune synapse signals by fusing a TCR targeting pMHC complex (Signal 1) with co-stimulatory signaling molecules (Signal 2) for targeted T cell modulation[45](index=45&type=chunk) - Preliminary clinical data from the CUE-101 Phase 1 trial supports the hypothesis of selective T cell activation with corresponding antitumor activity and clinical benefit[46](index=46&type=chunk) - The platform offers advantages over existing immunotherapies by providing 'off-the-shelf' biologics, direct in-patient administration, specific T cell targeting, broad disease target access, standard delivery, and cost-effective production[51](index=51&type=chunk) [Enhancing the Body's Capacity to Fight Cancer](index=9&type=section&id=Enhancing%20the%20Body%27s%20Capacity%20to%20Fight%20Cancer) The company believes its IL-2-based CUE-100 series can overcome the limitations of non-specific T cell modulation in cancer by selectively activating and amplifying only cancer-specific immune cells directly within the patient's body, aiming to achieve therapeutically effective dose levels with better tolerability compared to broad immune activation strategies - The IL-2-based CUE-100 series aims to selectively activate and amplify cancer-specific immune cells directly in the patient's body, addressing the challenge of non-specific T cell modulation[50](index=50&type=chunk)[51](index=51&type=chunk) - This selective targeting is expected to achieve well-tolerated and therapeutically effective dose levels, offering clinical advantages over competing immunotherapy approaches[50](index=50&type=chunk)[51](index=51&type=chunk) [IL-2 Therapy Challenges](index=10&type=section&id=IL-2%20Therapy%20Challenges) Current IL-2 therapies face challenges due to lack of selectivity and indiscriminate immune activation, leading to poor tolerability and limited therapeutic dosing, while the CUE-100 series Immuno-STATs are engineered with an affinity-attenuated IL-2 variant to selectively deliver IL-2 to tumor-specific T cells, activated only when their TCR is engaged with the Immuno-STAT's pHLA component, thus enabling specific activation and amplification of cancer-relevant T cells - Wild-type IL-2 and its variants indiscriminately engage T cells, leading to poor tolerability and limited therapeutic dosing ranges due to non-selective immune activation[52](index=52&type=chunk) - The CUE-100 series Immuno-STATs are engineered with an affinity-attenuated IL-2 variant, designed to selectively act only on tumor-specific T cells whose TCR is engaged to the pHLA component[53](index=53&type=chunk) - This concurrent signaling (HLA-epitope/TCR and IL-2 co-stimulatory) enables selective and specific activation and amplification of cancer-relevant T cells[53](index=53&type=chunk) [CUE-101](index=10&type=section&id=CUE-101) CUE-101 is the company's lead product candidate from the CUE-100 series, designed as a fusion protein biologic to target and activate antigen-specific T cells against HPV-driven cancers, incorporating an IL-2 variant and a peptide-MHC complex (HLA-A*02:01) with a dominant peptide from the HPV-16 E7 protein, a key driver of tumorigenesis - CUE-101 is a fusion protein biologic from the CUE-100 series, designed to target and activate antigen-specific T cells for HPV-driven cancers[54](index=54&type=chunk) - Its design includes an IL-2 variant and a pMHC composed of HLA-A*02:01 complexed with a dominant peptide from the HPV-16 E7 protein, a primary driver of tumorigenesis[54](index=54&type=chunk) - Extensive in vitro and in vivo preclinical studies with CUE-101 have been published in Clinical Cancer Research[56](index=56&type=chunk) [CUE-101 Clinical Development](index=11&type=section&id=CUE-101%20Clinical%20Development) CUE-101 is undergoing multiple clinical trials for HPV-driven cancers, including a Phase 1 monotherapy trial for second-line and beyond HPV+R/M HNSCC, a Phase 1 combination trial with KEYTRUDA for first-line HPV+R/M HNSCC, and an investigator-sponsored Phase 1b neoadjuvant trial, addressing a significant unmet medical need with approximately 24,600 new cases of HPV+ head and neck, cervical, and genitoanal cancers annually in the United States - CUE-101 is currently in a Phase 1 monotherapy trial for second-line and beyond HPV+R/M HNSCC and a Phase 1 combination trial with KEYTRUDA for first-line HPV+R/M HNSCC[57](index=57&type=chunk) - An investigator-sponsored Phase 1b neoadjuvant trial for locally advanced HPV+ HNSCC patients was initiated in the second half of 2021[57](index=57&type=chunk) - HPV+ cancers represent a significant unmet medical need, with approximately **24,600 cases** and **9,000 deaths annually** in the United States[58](index=58&type=chunk) [Phase 1 Monotherapy Trial of CUE-101](index=11&type=section&id=Phase%201%20Monotherapy%20Trial%20of%20CUE-101) The Phase 1 monotherapy trial of CUE-101 for HPV+R/M HNSCC completed its dose escalation phase in June 2021, with no maximum tolerated dose identified across seven cohorts, demonstrating a favorable tolerability profile, and the expansion stage is enrolling patients at the 4 mg/kg recommended Phase 2 dose (RP2D), with preliminary results from 14 evaluable patients at RP2D showing one confirmed partial response lasting over 36 weeks and six patients with stable disease for at least 12 weeks, alongside an observed trend of enhanced overall survival - The dose escalation portion of the Phase 1 monotherapy trial for CUE-101 completed in June 2021, treating 38 patients across seven cohorts (0.06mg/kg to 8mg/kg) without identifying a maximum tolerated dose (MTD)[59](index=59&type=chunk) - At the recommended Phase 2 dose (RP2D) of **4 mg/kg**, 14 evaluable patients showed one confirmed partial response (PR) lasting over **36 weeks** and six patients with confirmed stable disease (SD) lasting at least **12 weeks**[59](index=59&type=chunk) - Preliminary safety data from 45 patients as of January 25, 2022, indicates CUE-101 is well tolerated at RP2D, with common adverse events (fatigue, anemia, decreased lymphocyte counts) consistent with IL-2 administration or CPIs, and no observations of capillary leak syndrome or severe cytokine storm[60](index=60&type=chunk)[63](index=63&type=chunk) [Phase 1 Trial of CUE-101 in Combination with KEYTRUDA](index=12&type=section&id=Phase%201%20Trial%20of%20CUE-101%20in%20Combination%20with%20KEYTRUDA) The Phase 1 combination trial of CUE-101 with KEYTRUDA for first-line R/M HNSCC, initiated in Q4 2020, has shown encouraging early signs of activity, with no dose-limiting toxicities observed across three cohorts, and three out of three patients in cohort two (2 mg/kg) demonstrated reductions in target tumor lesions, with two patients in dose escalation (cohorts two and three) having ongoing, confirmed partial responses - The Phase 1 combination trial of CUE-101 with KEYTRUDA for first-line R/M HNSCC was initiated in Q4 2020, with the first patient dosed in Q1 2021[65](index=65&type=chunk) - No dose-limiting toxicities have been observed in the three cohorts to date[65](index=65&type=chunk) - Early signs of activity include reductions in target tumor lesions for **three out of three patients** in cohort two (2 mg/kg) and two ongoing, confirmed partial responses among four patients treated in dose escalation (cohorts two and three)[65](index=65&type=chunk) [Other Applications of Immuno-STATs to Oncology](index=13&type=section&id=Other%20Applications%20of%20Immuno-STATs%20to%20Oncology) The Immuno-STAT platform's modularity is being leveraged to develop additional oncology candidates like CUE-102 and CUE-103, and the Neo-STAT platform, to address tumor heterogeneity and escape mechanisms, with Neo-STAT, with its 'empty' MHC pocket, offering flexibility for targeting multiple tumor antigens, neo-antigens, and post-translationally modified antigens, potentially enhancing production efficiency and enabling personalized cancer immunotherapy - The Immuno-STAT platform's modularity and versatility are being leveraged to design and develop additional Immuno-STATs, including CUE-102 and CUE-103, to address tumor heterogeneity and escape mechanisms[67](index=67&type=chunk) - The Neo-STAT™ platform, a derivative scaffold with a stable 'peptide-less' MHC pocket, allows for chemical attachment of defined peptides post-manufacturing, offering greater flexibility for targeting multiple tumor epitopes and potentially personalized neo-antigen strategies[67](index=67&type=chunk)[75](index=75&type=chunk) - Significant progress has been made with the Neo-STAT platform, including feasibility proof of concept and experimental data demonstrating activation and expansion of primary human T cells with HLA-A02 Neo-STAT molecules[76](index=76&type=chunk) [CUE-102](index=13&type=section&id=CUE-102) CUE-102, part of the CUE-100 series, utilizes the same framework as CUE-101 but targets the Wilm's tumor protein (WT1), an oncofetal antigen over-expressed in over 20 different cancers, with preclinical data supporting selective WT1-specific T cell activation, expansion, and cytotoxic killing, and an IND filing for CUE-102 is anticipated by the end of Q1 2022 - CUE-102 leverages the CUE-101 framework but targets WT1, an oncofetal antigen over-expressed in more than **20 different cancers**, including solid tumors and hematologic malignancies[68](index=68&type=chunk) - Preclinical data demonstrates ex-vivo expansion of WT1-specific T cells from human donors and in vivo expansion in transgenic mice, along with polyfunctional effector function and cytotoxic killing of target cells[69](index=69&type=chunk) - An Investigational New Drug (IND) application for CUE-102 is anticipated to be filed by the end of the first quarter of 2022[68](index=68&type=chunk) [CUE-103](index=14&type=section&id=CUE-103) CUE-103 is a CUE-100 series Immuno-STAT being developed to target the KRAS G12V mutation, a primary tumor driver mutation found in various solid tumor types like colorectal, lung, and pancreatic cancers, with preclinical data demonstrating the feasibility of producing HLA-A11 Immuno-STATs with functional engagement and activity on targeted T cells specific for the G12V mutation, highlighting the platform's modularity - CUE-103 is a CUE-100 series Immuno-STAT targeting the KRAS G12V mutation, associated with many solid tumor types including colorectal carcinoma, lung cancer, and pancreatic cancer[74](index=74&type=chunk) - Preclinical data presented at SITC 2020 suggested the feasibility of producing HLA-A11 Immuno-STATs with functional engagement and activity on targeted T cells specific for the G12V mutation[74](index=74&type=chunk) - The development of CUE-103 underscores the modularity of the Immuno-STAT platform by extending its application to additional HLA alleles and modifying targeting epitopes[74](index=74&type=chunk) [Neo-STAT Platform](index=14&type=section&id=Neo-STAT%20Platform) The Neo-STAT™ platform is a next-generation derivative of the CUE-100 series, featuring a 'peptide-less' MHC pocket that allows for covalent attachment of defined peptides post-manufacturing, designed to significantly enhance productivity, increase flexibility for targeting multiple tumor antigens (including neo-antigens and post-translationally modified antigens), and potentially enable personalized neo-antigen strategies in cancer immunotherapy, with feasibility proof-of-concept achieved, demonstrating T cell activation with various epitopes - The Neo-STAT™ platform is a next-generation derivative approach designed to enhance productivity and flexibility by generating a 'peptide-less' MHC pocket within the Immuno-STAT scaffold for post-manufacturing peptide conjugation[75](index=75&type=chunk) - This platform has the potential to target multiple tumor antigens, neo-antigens, and post-translationally modified antigens, and could enable personalized neo-antigen strategies in cancer immunotherapy[75](index=75&type=chunk) - Significant progress includes feasibility proof of concept, creation of a master cell line, and experimental data demonstrating expansion and activation of primary human T cells with HLA-A02 Neo-STAT molecules deploying different T cell epitopes[76](index=76&type=chunk) [Application of Immuno-STATs Outside of Oncology: CUE-200, CUE-300 and CUE-400](index=15&type=section&id=Application%20of%20Immuno-STATs%20Outside%20of%20Oncology%3A%20CUE-200%2C%20CUE-300%20and%20CUE-400) Beyond oncology, the Immuno-STAT platform has developed three additional biologic series: CUE-200 for chronic infectious diseases (targeting T cell exhaustion), CUE-300 for autoimmune diseases with known autoantigens (incorporating PD-L1 co-modulator), and CUE-400 for autoimmune diseases with diverse/unknown autoantigens (expanding induced regulatory T cells), but due to strategic prioritization on oncology, the company is actively seeking third-party support for these non-oncology programs - The CUE-200 series focuses on cell surface receptors (CD80 and/or 4-1BBL) to address T cell exhaustion in chronic infections[31](index=31&type=chunk) - The CUE-300 series for autoimmune diseases incorporates the inhibitory PD-L1 co-modulator for selective inhibition of autoreactive T cells, with data generated through a collaboration with Merck[31](index=31&type=chunk)[80](index=80&type=chunk) - The CUE-400 series, also for autoimmune diseases, represents novel bispecific molecules designed to selectively expand induced regulatory T cells (iTregs), with CUE-401 incorporating IL-2 and TGF-beta[31](index=31&type=chunk)[82](index=82&type=chunk) - Due to strategic focus on oncology, the company is actively seeking third-party support (partnerships, collaborations, or alternative funding) to further develop these non-oncology programs[31](index=31&type=chunk)[84](index=84&type=chunk) [Our License Agreement with Einstein](index=16&type=section&id=Our%20License%20Agreement%20with%20Einstein) The company holds an exclusive worldwide license from Albert Einstein College of Medicine (Einstein License) for patent rights related to its core Immuno-STAT technology platform, which is a royalty-bearing license including milestone payments (up to **$1.85 million** per product/indication, **$5.75 million** cumulative sales) and annual maintenance fees, and the company issued 671,572 shares of common stock to Einstein and is obligated to meet specific diligence milestones, all of which have been met as of the report date - The company holds an exclusive worldwide, royalty-bearing license from Albert Einstein College of Medicine for patent rights related to its core technology platform for engineering biologics to control T cell activity[85](index=85&type=chunk)[86](index=86&type=chunk) - Milestone payments can aggregate up to **$1.85 million** for each Licensed Product and new indication, plus up to **$5.75 million** for cumulative sales of all Licensed Products, with a **$150,000** milestone payment made for CUE-101 IND approval[87](index=87&type=chunk) - The company is obligated to meet certain due diligence milestones, including initiating clinical trials and submitting FDA applications, and has met all required milestones as of the report date[93](index=93&type=chunk)[94](index=94&type=chunk) [Our Collaboration Agreement with Merck](index=17&type=section&id=Our%20Collaboration%20Agreement%20with%20Merck) The company entered into an exclusive patent license and research collaboration agreement with Merck in November 2017 to research and develop Immuno-STAT drug product candidates for certain autoimmune disease indications, with Merck providing a **$2.5 million** upfront payment and the company eligible for up to **$371 million** in research, development, regulatory, and commercial milestones, plus tiered royalties, and the research collaboration term expired on December 31, 2021, with discussions ongoing for a potential path forward - An exclusive patent license and research collaboration agreement was established with Merck in November 2017 for autoimmune disease indications, with Merck funding further development of selected Immuno-STAT candidates[95](index=95&type=chunk) - The company received a **$2.5 million** upfront payment and is eligible for up to **$101 million** in R&D milestones, **$120 million** in regulatory milestones, and **$150 million** in commercial milestones, in addition to tiered single-digit royalties[98](index=98&type=chunk) - The research collaboration term was extended through December 31, 2021, and has since expired, with ongoing discussions with Merck to define a clinical candidate[100](index=100&type=chunk) [Our Collaboration Agreement with LG Chem](index=18&type=section&id=Our%20Collaboration%20Agreement%20with%20LG%20Chem) The company has a collaboration, license, and option agreement with LG Chem (November 2018) for oncology Immuno-STATs, granting LG Chem an exclusive license to develop, manufacture, and commercialize CUE-101 and two additional cancer antigens (WT1 selected) in the LG Chem Territory (Asia/Australia), while the company retains US and global rights, and LG Chem made a **$5.0 million** upfront payment and a **$5.0 million** equity investment, with potential for up to **$400 million** in milestones and tiered single-digit royalties, and the company has earned **$6.75 million** in milestones to date under this agreement - A collaboration, license, and option agreement with LG Chem (effective November 6, 2018) grants LG Chem exclusive rights to develop, manufacture, and commercialize CUE-101 and two additional cancer antigens (WT1 selected) in the LG Chem Territory (Australia, Japan, Republic of Korea, Singapore, Malaysia, Vietnam, Thailand, Philippines, Indonesia, China, Taiwan)[101](index=101&type=chunk)[102](index=102&type=chunk)[108](index=108&type=chunk) - LG Chem provided a **$5.0 million** non-refundable upfront payment and purchased approximately **$5.0 million** of the company's common stock[103](index=103&type=chunk) - The company is eligible to receive additional aggregate payments of approximately **$400 million** for research, development, regulatory, and commercial milestones, plus tiered single-digit royalties on net sales in the LG Chem Territory, with milestones earned including **$2.5 million** (CUE-101 IND acceptance), **$1.25 million** (preclinical candidate selection), and **$3.0 million** (clinical product candidate confirmation)[103](index=103&type=chunk)[105](index=105&type=chunk) [Our Intellectual Property](index=19&type=section&id=Our%20Intellectual%20Property) The company's business relies heavily on its intellectual property, including **76 issued patents** and numerous pending applications (**52 US, 20 PCT, 190 foreign**) covering its Immuno-STAT and Neo-STAT platforms, specific biologics, and treatment methods, with these patents set to expire no earlier than 2033-2042, and Cue products protected until at least December 2037, and the company actively protects its IP through patents, trade secrets, and confidentiality agreements, but acknowledges risks of challenges, circumvention, and varying international protection - As of December 31, 2021, the company owned or licensed **76 issued patents**, **52 pending U.S. patent applications**, **20 pending international PCT applications**, and **190 pending foreign patent applications**[109](index=109&type=chunk) - These intellectual property rights protect the Immuno-STAT platform, Neo-STAT platform, CAR-T and ex-vivo applications, RDI-STAT platform, specific biologic molecules, drug product candidates, and methods of treatment[109](index=109&type=chunk) - Granted patents generally have a term of **20 years** from their U.S. non-provisional priority filing date, with those specifically covering Cue products expiring no earlier than December 2037, subject to extensions[111](index=111&type=chunk) [Competition](index=20&type=section&id=Competition) The biopharmaceutical industry is highly competitive, with the company facing rivals from established pharmaceutical and biotechnology firms, academic institutions, and government agencies, and competitors are developing various immunotherapy technologies, including bi-specific antibodies, cell therapies, antibody-drug conjugates, immune checkpoint inhibitors, and modified cytokines, and the company believes its antigen-specific targeting of cytokines, coupled with genetically modified IL-2, provides a competitive advantage, but acknowledges the risk of new products, price competition, and the need to demonstrate superior efficacy, convenience, tolerability, or safety - The company faces significant competition from established and emerging pharmaceutical and biotechnology companies, academic institutions, and governmental agencies[112](index=112&type=chunk) - Competitors are developing various immunotherapy technologies, including bi-specific antibodies, cell therapies, antibody-drug conjugates, immune checkpoint inhibitors, and modified cytokines[113](index=113&type=chunk) - The company believes its approach of antigen-specific targeting of cytokines, such as IL-2, by engineering proteins with a peptide-MHC targeting moiety coupled to genetically modified cytokines, provides a competitive advantage[113](index=113&type=chunk) [Government Regulation and Licensure of Products](index=21&type=section&id=Government%20Regulation%20and%20Licensure%20of%20Products) The company's products are subject to extensive government regulation in the United States (FDA) and internationally (e.g., European Union), covering all stages from research and development to commercialization, including stringent requirements for preclinical and clinical testing, manufacturing (GMP), marketing approval (BLA/MAA), post-approval monitoring, and pricing/reimbursement, with various expedited review programs existing but not guaranteeing approval, and compliance with these complex and evolving regulations, including those for orphan drugs, biosimilars, and companion diagnostics, is critical and resource-intensive, with non-compliance leading to significant penalties - Pharmaceutical products, including biologics, are extensively regulated by government authorities in the United States (FDA) and other countries (e.g., European Union) across all stages from research to commercialization[120](index=120&type=chunk) - The regulatory process involves preclinical testing (GLP), manufacturing under GMP, IND applications, IRB approval, multi-phase clinical trials (GCP), BLA/MAA submissions, and post-approval compliance, requiring substantial time and financial resources[121](index=121&type=chunk) - Expedited review programs (Fast Track, Breakthrough Therapy, Priority Review, Accelerated Approval, Regenerative Advanced Therapy) exist but do not change approval standards or guarantee faster review[161](index=161&type=chunk)[162](index=162&type=chunk)[165](index=165&type=chunk) [Human Capital](index=39&type=section&id=Human%20Capital) As of December 31, 2021, the company had **57 full-time** and **two part-time employees**, primarily located in Cambridge, Massachusetts, and emphasizes a workplace culture of respect, collaboration, and integrity, focusing on attracting, developing, and retaining diverse talent through competitive benefits and professional development, and in response to the COVID-19 pandemic, safety protocols such as remote work and travel restrictions were implemented and largely remained in place during 2021 - As of December 31, 2021, the company had **57 full-time** and **two part-time employees**, with most located in Cambridge, Massachusetts[245](index=245&type=chunk) - The company is committed to fostering a workplace that encourages respect, collaboration, communication, transparency, and integrity, and focuses on attracting, developing, and retaining diverse talent[246](index=246&type=chunk) - During 2020 and 2021, additional safety protocols were implemented due to the COVID-19 pandemic, including remote working standards, non-essential travel pauses, and limits on in-person meetings[247](index=247&type=chunk) [Status as an Emerging Growth Company](index=39&type=section&id=Status%20as%20an%20Emerging%20Growth%20Company) The company is classified as an "emerging growth company" (EGC) under the JOBS Act and will retain this status until December 31, 2022, having irrevocably opted out of the extended transition period for new accounting standards but benefiting from other EGC provisions, such as exemptions from auditor attestation for internal controls and reduced executive compensation disclosure, and is also a "smaller reporting company," which provides similar reduced disclosure obligations - The company is an "emerging growth company" (EGC) as defined by the JOBS Act and will remain so until December 31, 2022[248](index=248&type=chunk)[448](index=448&type=chunk) - It has irrevocably elected to opt out of the extended transition period for complying with new or revised financial accounting standards[250](index=250&type=chunk)[449](index=449&type=chunk) - As an EGC, the company benefits from reduced disclosure obligations, including exemption from auditor attestation requirements for internal control over financial reporting and reduced executive compensation disclosure[250](index=250&type=chunk)[448](index=448&type=chunk) [Item 1A. Risk Factors](index=41&type=section&id=Item%201A.%20Risk%20Factors) The company faces significant risks inherent to a clinical-stage biopharmaceutical company, including a history of operating losses and no commercial revenue, substantial dependence on the success of its limited clinical-stage drug candidates, and challenges in securing additional financing, with operational risks including the impact of the COVID-19 pandemic, potential adverse events in clinical trials, intense competition, reliance on third-party CROs and CMOs, and the need to protect intellectual property, and extensive government regulation, healthcare reform, and compliance with various laws (e.g., anti-kickback, HIPAA) also posing substantial risks to its business, financial condition, and future profitability - The company is a clinical-stage biopharmaceutical company with no history of commercial revenue, a history of operating losses (accumulated deficit of approximately **$197.4 million** as of December 31, 2021), and may never achieve profitability[253](index=253&type=chunk)[254](index=254&type=chunk) - The business is substantially dependent on the success of its drug product candidates, with only CUE-101 currently in clinical trials, and significant additional R&D and clinical testing are required for regulatory approval and commercialization[260](index=260&type=chunk)[261](index=261&type=chunk) - Key risks include potential adverse events or toxicities in clinical trials, significant competition from other biopharmaceutical companies, reliance on third parties for clinical trials and manufacturing, and the inability to protect intellectual property[272](index=272&type=chunk)[300](index=300&type=chunk)[311](index=311&type=chunk)[323](index=323&type=chunk) - The company is subject to extensive government regulation, including the lengthy and unpredictable marketing approval process, potential competition from biosimilars, and compliance with healthcare fraud and abuse laws, which could lead to substantial penalties[351](index=351&type=chunk)[364](index=364&type=chunk)[394](index=394&type=chunk) - Future losses and negative cash flow are anticipated, requiring additional financing which may dilute stockholders, restrict operations, or encumber assets, and the company's loan agreement with Silicon Valley Bank imposes covenants and restrictions[436](index=436&type=chunk)[437](index=437&type=chunk)[438](index=438&type=chunk)[439](index=439&type=chunk)[444](index=444&type=chunk)[445](index=445&type=chunk) [Item 1B. Unresolved Staff Comments](index=71&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) This section indicates that there are no unresolved staff comments from the SEC regarding the company's previous filings [Item 2. Properties](index=72&type=section&id=Item%202.%20Properties) The company's principal office and laboratory facilities are located in Cambridge, Massachusetts, encompassing approximately **19,900 square feet**, with the lease for this space extended in October 2021 to March 2024, with monthly rental rates increasing from **$375,000** to **$388,000**, and additionally, the company leases three procedure and holding rooms for approximately **$61,000** per month until June 2022 - The company's principal office and laboratory space in Cambridge, Massachusetts, covers approximately **19,900 square feet**[476](index=476&type=chunk) - The lease term for the principal space was extended in October 2021 from June 2022 to March 2024[476](index=476&type=chunk) - Monthly rental rates for the principal space are **$375,000** until June 2022, increasing to **$388,000** for the remainder of the term, and additional laboratory space costs approximately **$61,000** per month until June 2022[476](index=476&type=chunk) [Item 3. Legal Proceedings](index=72&type=section&id=Item%203.%20Legal%20Proceedings) The company is not currently involved in any pending legal proceedings that are expected to have a material adverse effect on its business or financial condition, but it may, however, encounter various claims and legal actions in the ordinary course of business - The company is not currently a party to any pending legal proceedings that are believed to have a material adverse effect on its business or financial conditions[477](index=477&type=chunk) - The company may be subject to various claims and legal actions arising in the ordinary course of business from time to time[477](index=477&type=chunk) [Item 4. Mine Safety Disclosures](index=72&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company PART II [Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=73&type=section&id=Item%205.%20Market%20for%20Registrant%27s%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock has been listed on the Nasdaq Capital Market under the symbol "CUE" since January 2, 2018, with approximately **51 registered holders** as of March 7, 2022, and the company has never paid cash dividends and does not anticipate doing so in the foreseeable future, intending to reinvest earnings into the business, with dividend payments currently restricted by the terms of its Loan Agreement - The company's common stock has been listed on the Nasdaq Capital Market under the symbol "CUE" since January 2, 2018[480](index=480&type=chunk) - As of March 7, 2022, there were approximately **51 registered holders** of the company's common stock[481](index=481&type=chunk) - The company has never paid cash dividends and does not anticipate paying any in the foreseeable future, planning to reinvest all earnings into the business, and its ability to pay dividends is currently restricted by the Loan Agreement[482](index=482&type=chunk)[460](index=460&type=chunk) [Item 6. [Reserved.]](index=73&type=section&id=Item%206.%20%5BReserved.%5D) This item is reserved and contains no information [Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=74&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides an overview of the company's financial condition and operational results, highlighting its status as a clinical-stage biopharmaceutical company focused on oncology, with ongoing R&D and clinical trials, detailing the impact of the COVID-19 pandemic on operations and supply chain, outlining critical accounting policies, and discussing significant collaboration agreements with Merck and LG Chem, with the company reporting an increase in collaboration revenue but also higher operating expenses, resulting in a net loss, and liquidity primarily from equity offerings and collaboration payments, with existing cash expected to fund operations for the next 12 months, though additional capital will be needed - The company is a clinical-stage biopharmaceutical company prioritizing oncology programs (CUE-100 series) and seeking third-party support for non-oncology programs[485](index=485&type=chunk)[486](index=486&type=chunk) - The COVID-19 pandemic caused supply chain disruptions and delayed CUE-102 GMP manufacturing, impacting its IND filing date[489](index=489&type=chunk) - Collaboration revenue increased significantly in 2021, primarily due to cost sharing and a **$3.0 million** milestone from the LG Chem Collaboration Agreement[542](index=542&type=chunk) Consolidated Statements of Operations and Comprehensive Loss (Years Ended December 31) | Metric | 2021 (USD) | 2020 (USD) | |:---|:---|:---| | Collaboration revenue | $14,941,370 | $3,154,325 | | General and administrative expenses | $17,306,678 | $14,651,205 | | Research and development expenses | $41,346,765 | $33,545,705 | | Total operating expenses | $58,653,443 | $48,196,910 | | Loss from operations | $(43,712,073) | $(45,042,585) | | Interest income, net | $45,898 | $463,914 | | Provision for income taxes | $(495,000) | $(206,250) | | Net loss | $(44,161,175) | $(44,784,921) | | Comprehensive loss | $(44,168,306) | $(44,767,469) | | Net loss per common share – basic and diluted | $(1.41) | $(1.56) | | Weighted average common shares outstanding – basic and diluted | 31,285,418 | 28,688,625 | - The company's cash, cash equivalents, and marketable securities totaled approximately **$64.4 million** at December 31, 2021, down from **$84.9 million** at December 31, 2020, and management believes existing cash resources are sufficient for at least the next 12 months, but additional capital will be needed for future operations[553](index=553&type=chunk)[573](index=573&type=chunk)[574](index=574&type=chunk) [Overview](index=76&type=section&id=Overview) Cue Biopharma is a clinical-stage biopharmaceutical company focused on developing injectable biologics using its Immuno-STAT™ platform to selectively modulate T cells for cancer, chronic infectious diseases, and autoimmune disorders, with the company prioritizing its CUE-100 oncology series and actively seeking partnerships for its non-oncology programs, and it has not yet generated commercial revenue and requires additional capital for growth - The company is a clinical-stage biopharmaceutical company engineering novel injectable biologics to selectively engage and modulate targeted T cells using its Immuno-STAT™ platform[485](index=485&type=chunk) - Current strategic focus is on drug product candidates for treating cancer in the CUE-100 series, while actively seeking third-party support for non-oncology programs (CUE-200, CUE-300, CUE-400 series)[486](index=486&type=chunk) - The company has not yet commenced commercial revenue-generating operations, has limited cash flows, and will need additional capital to fund its growth and ongoing business[487](index=487&type=chunk) [The COVID-19 Pandemic](index=76&type=section&id=The%20COVID-19%20Pandemic) The COVID-19 pandemic led the company to implement precautionary measures like remote work and travel restrictions, and while these actions have not significantly impacted productivity, the company experienced supply chain disruptions for lab supplies, and notably, the manufacturing of GMP material for the CUE-102 drug candidate was delayed by approximately **six weeks** due to the Defense Production Act, pushing its IND filing from Q4 2021 to Q1 2022 - The company implemented precautionary measures due to COVID-19, including remote working standards and travel restrictions, which have not significantly impacted productivity or operations[488](index=488&type=chunk) - Supply chain disruptions for lab supplies used in preclinical research have been experienced[489](index=489&type=chunk) - Manufacture of GMP material for the CUE-102 drug product candidate was delayed by approximately **six weeks** due to the Defense Production Act, shifting its anticipated IND filing from Q4 2021 to Q1 2022[489](index=489&type=chunk) [Plan of Operation](index=76&type=section&id=Plan%20of%20Operation) As a development-stage company, the majority of its activities are dedicated to research and development, with the plan to maximize the value of Immuno-STAT drug candidates through R&D, early-stage clinical development, and strategic partnerships for later clinical stages, alongside robust patent protection - As a development-stage company, the majority of business activities are devoted to furthering research and development[492](index=492&type=chunk) - The company intends to maximize the value of its Immuno-STAT drug product candidates by focusing on research, testing, optimization, pilot studies, early-stage clinical development, and potentially partnering for later clinical stages[490](index=490&type=chunk) - A fundamental part of the corporate development strategy is to establish strategic partnerships with leading pharmaceutical or biotechnology organizations[493](index=493&type=chunk) [Critical Accounting Policies and Significant Judgments and Estimates](index=77&type=section&id=Critical%20Accounting%20Policies%20and%20Significant%20Judgments%20and%20Estimates) The preparation of financial statements requires management to make significant estimates and assumptions, particularly in revenue recognition (ASC 606), research and development costs, stock-based compensation, and income taxes (ASC 740), with these estimates, based on historical experience and forecasts, affecting reported asset/liability amounts and revenue/expense recognition, and no material changes to critical accounting policies occurred in 2021 - Financial statements are prepared in accordance with U.S. GAAP, requiring management to make estimates and assumptions affecting reported amounts of assets, liabilities, revenue, and expenses[494](index=494&type=chunk) - Critical accounting policies include revenue recognition (ASC 606), research and development costs, stock-based compensation, and income taxes (ASC 740)[495](index=495&type=chunk)[496](index=496&type=chunk)[499](index=499&type=chunk)[503](index=503&type=chunk)[509](index=509&type=chunk) - There were no material changes to the company's critical accounting policies and estimates as of December 31, 2021[495](index=495&type=chunk) [Significant Contracts and Agreements Related to Research and Development Activities](index=79&type=section&id=Significant%20Contracts%20and%20Agreements%20Related%20to%20Research%20and%20Development%20Activities) The company has significant R&D agreements, including an exclusive license with Albert Einstein College of Medicine for its core technology, requiring milestone payments and annual fees, and collaboration agreements with Merck (for autoimmune diseases) and LG Chem (for oncology) involve upfront payments, potential milestones, and royalties, with the Merck agreement's research term expiring in December 2021, while the LG Chem agreement has yielded several milestone payments and ongoing cost-sharing - The Einstein License Agreement grants the company exclusive worldwide rights to its core technology platform, requiring significant milestone payments and annual maintenance fees[514](index=514&type=chunk)[515](index=515&type=chunk) - The Merck Collaboration Agreement, for autoimmune disease programs, provided a **$2.5 million** upfront payment and potential milestones up to **$371 million**, and its research term expired on December 31, 2021[521](index=521&type=chunk)[523](index=523&type=chunk)[526](index=526&type=chunk) - The LG Chem Collaboration Agreement, for oncology Immuno-STATs in Asian markets, included a **$5.8 million** upfront payment and **$5.0 million** equity investment, with potential milestones up to **$400 million**, and the company recognized approximately **$12.8 million** in revenue from this agreement in 2021[528](index=528&type=chunk)[530](index=530&type=chunk)[533](index=533&type=chunk) [Results of Operations](index=82&type=section&id=Results%20of%20Operations) For the years ended December 31, 2021 and 2020, the company reported a net loss of approximately **$44.16 million** and **$44.78 million**, respectively, with collaboration revenue significantly increasing to **$14.94 million** in 2021 from **$3.15 million** in 2020, driven by the LG Chem agreement, and operating expenses also rose, with general and administrative expenses increasing to **$17.31 million** and research and development expenses to **$41.35 million** in 2021, primarily due to higher compensation, professional fees, and lab costs, and interest income decreased substantially due to marketable securities maturing Consolidated Statements of Operations and Comprehensive Loss (Years Ended December 31) | Metric | 2021 (USD) | 2020 (USD) | |:---|:---|:---|\n| Collaboration revenue | $14,941,370 | $3,154,325 | | General and administrative expenses | $17,306,678 | $14,651,205 | | Research and development expenses | $41,346,765 | $33,545,705 | | Total operating expenses | $58,653,443 | $48,196,910 | | Loss from operations | $(43,712,073) | $(45,042,585) | | Interest income, net | $45,898 | $463,914 | | Provision for income taxes | $(495,000) | $(206,250) | | Net loss | $(44,161,175) | $(44,784,921) | | Comprehensive loss | $(44,168,306) | $(44,767,469) | | Net loss per common share – basic and diluted | $(1.41) | $(1.56) | | Weighted average common shares outstanding – basic and diluted | 31,285,418 | 28,688,625 | - Collaboration revenue increased by approximately **$11.787 million** in 2021, primarily due to cost sharing and a **$3.0 million** milestone from the LG Chem Collaboration Agreement[542](index=542&type=chunk) - General and administrative expenses increased by approximately **$2.656 million** in 2021, mainly due to higher stock-based compensation, professional fees, and employee/board compensation[543](index=543&type=chunk) - Research and development expenses increased by approximately **$7.801 million** in 2021, driven by higher laboratory and drug substance manufacturing costs, employee/advisory board compensation, and other professional fees[546](index=546&type=chunk) [Liquidity and Capital Resources](index=84&type=section&id=Liquidity%20and%20Capital%20Resources) The company's liquidity is primarily supported by equity offerings, collaboration agreements, and a loan from Silicon Valley Bank, and as of December 31, 2021, unrestricted cash, cash equivalents, and marketable securities totaled approximately **$64.4 million**, a decrease from **$84.9 million** in 2020, and while these resources are estimated to fund operations for the next 12 months, significant additional capital will be required for ongoing R&D, clinical trials, and potential commercialization, and the company actively uses ATM equity offerings and recently secured a **$10.0 million** term loan with an option for an additional **$10.0 million** - The company's working capital is financed through private and public equity offerings, 'at-the-market' (ATM) equity sales, cash from Merck and LG Chem collaboration agreements, and a loan from Silicon Valley Bank (SVB)[553](index=553&type=chunk) Cash, Cash Equivalents, and Restricted Cash (Years Ended December 31) | Metric | 2021 (USD) | 2020 (USD) | |:---|:---|:---|\n| Net cash used in operating activities | $(38,837,166) | $(32,494,034) | | Net cash provided by investing activities | $9,108,511 | $4,455,874 | | Net cash provided by financing activities | $19,233,322 | $58,614,263 | | Net (decrease) increase in cash, cash equivalents, and restricted cash | $(10,495,333) | $30,576,103 | | Cash, cash equivalents, and restricted cash at end of year | $64,520,800 | $75,016,133 | - As of December 31, 2021, unrestricted cash, cash equivalents, and marketable securities totaled approximately **$64.4 million**, which is estimated to fund operating requirements for at least the next **12 months**[553](index=553&type=chunk)[573](index=573&type=chunk) - The company will need to raise additional capital or incur indebtedness to continue funding future operations, with funding requirements dependent on R&D progress, clinical trials, regulatory approvals, and commercialization efforts[574](index=574&type=chunk) [Principal Commitments](index=88&type=section&id=Principal%20Commitments) The company's principal commitments include multi-year operating leases for its Cambridge, Massachusetts office and laboratory spaces, which were amended to extend terms and adjust rental rates, and as of December 31, 2021, future minimum lease payments totaled approximately **$10.69 million**, and additionally, the company has a manufacturing agreement with Catalent Pharma Solutions, LLC, with approximately **$1.255 million** owed as of December 31, 2021, and ongoing milestone-based commitments under the Einstein License Agreement - The company has multi-year, noncancelable operating lease agreements for its Cambridge, Massachusetts office and laboratory space, with the Laboratory and Office Lease extended to March 14, 2024[584](index=584&type=chunk)[769](index=769&type=chunk) Future Minimum Lease Payments (as of December 31, 2021) | Year | Amount (USD) | |:---|:---|\n| 2022 | $4,931,675 | | 2023 | $4,754,796 | | 2024 | $1,004,739 | | Total lease payments | $10,691,210 | | Less: present value discount | $(638,358) | | Present value of lease payments | $10,052,853 | - As of December 31, 2021, the company owed Catalent Pharma Solutions, LLC approximately **$1.255 million** for contracted manufacturing services related to CUE-102 materials[586](index=586&type=chunk) - Commitments under the Einstein License Agreement are based on the attainment of future milestones, with aggregate milestone payments potentially reaching up to **$1.85 million** per Licensed Product/new indication and **$5.75 million** for cumulative sales[762](index=762&type=chunk) [Item 7A. Quantitative and Qualitative Disclosures About Market Risk.](index=87&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk.) As a smaller reporting company, the registrant is not required to provide quantitative and qualitative disclosures about market risk [Item 8. Financial Statements and Supplementary Data.](index=87&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data.) This section refers to the company's financial statements and related notes, which are presented starting on page F-1 (document page 91) of this Annual Report on Form 10-K - The company's financial statements and related notes are included starting on page F-1 of this Annual Report on Form 10-K[589](index=589&type=chunk) [Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.](index=87&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20with%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure.) The company reports that there have been no changes in or disagreements with accountants on accounting and financial disclosure - There are no changes in and disagreements with accountants on accounting and financial disclosure[590](index=590&type=chunk) [Item 9A. Controls and Procedures.](index=87&type=section&id=Item%209A.%20Controls%20and%20Procedures.) As of December 31, 2021, management, with the participation of its principal executive and financial officers, concluded that the company's disclosure controls and procedures were effective, and management also assessed and concluded that its internal control over financial reporting was effective based on the COSO framework, and the annual report does not include an auditor attestation report due to the company's status as an emerging growth company - As of December 31, 2021, the company's management, including its principal executive and financial officers, concluded that its disclosure controls and procedures were effective[592](index=592&type=chunk) - Management assessed and concluded that the company's internal control over financial reporting was effective as of December 31, 2021, based on the COSO Internal Control Integrated Framework (2013)[593](index=593&type=chunk) - This annual report does not include an attestation report from the registered public accounting firm regarding internal control over financial reporting, due to the company's status as an emerging growth company[594](index=594&type=chunk) [Item 9B. Other Information.](index=87&type=section&id=Item%209B.%20Other%20Information.) This item is not applicable and contains no additional information [Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections.](index=87&type=section&id=Item%209C.%20Disclosure%20Regarding%20Foreign%20Jurisdictions%20that%20Prevent%20Inspections.) This item is not applicable to the company PART III [Item 10. Directors, Executive Officers and Corporate Governance.](index=88&type=section&id=Item%2010.%20Directors%2C%20Executive%20Officers%20and%20Corporate%20Governance.) The information required for this item, pertaining to directors, executive officers, and corporate governance, is incorporated by reference from the company's definitive proxy statement on Schedule 14A, to be filed within **120 days** after the fiscal year ended December 31, 2021 - Information regarding directors, executive officers, and corporate governance is incorporated by reference from the definitive proxy statement on Schedule 14A[600](index=600&type=chunk) - The proxy statement is to be filed with the SEC within **120 days** after the end of the fiscal year ended December 31, 2021[600](index=600&type=chunk) [Item 11. Executive Compensation](index=88&type=section&id=Item%2011.%20Executive%20Compensation) The information required for this item, concerning executive compensation, is incorporated by reference from the company's definitive proxy statement on Schedule 14A, which will be filed within **120 days** after the fiscal year ended December 31, 2021 - Information regarding executive compensation is incorporated by reference from the definitive proxy statement on Schedule 14A[601](index=601&type=chunk) - The proxy statement is to be filed with the SEC within **120 days** after the end of the fiscal year ended December 31, 2021[601](index=601&type=chunk) [Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholders Matters.](index=88&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholders%20Matters.) The information required for this item, covering security ownership of certain beneficial owners and management, and related stockholder matters, is incorporated by reference from the company's definitive proxy statement on Schedule 14A, to be filed within **120 days** after the fiscal year ended December 31, 2021 - Information regarding security ownership of certain beneficial owners and management, and related stockholder matters, is incorporated by reference from the definitive proxy statement on Schedule 14A[602](index=602&type=chunk) - The proxy statement is to be filed with the SEC within **120 days** after the end of the fiscal year ended December 31, 2021[602](index=602&type=chunk) [Item 13. Certain Relationships and Related Transactions, and Director Independence](index=88&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions%2C%20and%20Director%20Independence) The information required for this item, concerning certain relationships and related transactions, and director independence, is incorporated by reference from the company's definitive proxy statement on Schedule 14A, to be filed within **120 days** after the fiscal year ended December 31, 2021 - Information regarding certain relationships and related transactions, and director independence, is incorporated by reference from the definitive proxy statement on Schedule 14A[603](index=603&type=chunk) - The proxy statement is to be filed with the SEC within **120 days** after the end of the fiscal year ended December 31, 2021[603](index=603&type=chunk) [Item 14. Principal Accountant Fees and Services](index=88&type=section&id=Item%2014.%20Principal%20Accountant%20Fees%20and%20Services) The information required for this item, detailing principal accountant fees and services, is incorporated by reference from the company's definitive proxy statement on Schedule 14A, to be filed within **120 days** after the fiscal year ended December 31, 2021 - Information regarding principal accountant fees and services is incorporated by reference from the definitive proxy statement on Schedule 14A[604](index=604&type=chunk) - The proxy statement is to be filed with the SEC within **120 days** after the end of the fiscal year ended December 31, 2021[604](index=604&type=chunk) PART IV [Item 15. Exhibits, Financial Statements and Schedules](index=89&type=section&id=Item%2015.%20Exhibits%2C%20Financial%20Statements%20and%20Schedules) This section lists the documents filed as part of the report, including the financial statements and supplementary data (starting on page F-1), and a comprehensive list of exhibits, which include various corporate documents, agreements (e.g., license, collaboration, employment), and certifications, with some portions subject to confidential treatment or omission - The report includes financial statements and supplementary data, which are incorporated by reference from Item 8 and begin on page F-1 (document page 91)[787](index=787&type=chunk) - A comprehensive list of exhibits is filed as part of this Annual Report on Form 10-K, detailing various corporate and contractual documents[788](index=788&type=chunk) - Exhibits include the Amended and Restated Certificate of Incorporation, Bylaws, specimen stock certificates, warrants, registration rights agreements, collaboration agreements (Merck, LG Chem), employment agreements, and certifications[788](index=788&type=chunk)[790](index=790&type=chunk)[794](index=794&type=chunk) [Item 16. Form 10-K Summary](index=92&type=section&id=Item%2016.%20Form%2010-K%20Summary) This item is not applicable to the company Financial Statements [Reports of Independent Registered Public Accounting Firm](index=92&type=section&id=Reports%20of%20Independent%20Registered%20Public%20Accounting%20Firm) RSM US LLP, the independent registered public accounting firm, issued an unqualified opinion on the consolidated financial statements of Cue Biopharma, Inc. for the years ended December 31, 2021 and 2020, with the audit conducted in accordance with PCAOB standards, confirming that the financial statements present fairly, in all material respects, the company's financial position and results of operations in conformity with U.S. GAAP, and the firm has served as the company's auditor since 2018 - RSM US LLP issued an unqualified opinion on the consolidated financial statements for the years ended December 31, 2021 and 2020[610](index=610&type=chunk) - The financial statements present fairly, in all material respects, the financial position and results of operations in conformity with U.S. GAAP[610](index=610&type=chunk) - The audit was conducted in accordance with PCAOB standards, but an audit of internal control over financial reporting was not performed as the company is not required to have one[612](index=612&type=chunk) [Consolidated Balance Sheets](index=93&type=section&id=Consolidated%20Balance%20Sheets) The consolidated balance sheets show the company's financial position as of December 31, 2021, and 2020, with total assets decreasing from **$99.53 million** in 2020 to **$83.40 million** in 2021, primarily due to a reduction in cash, cash equivalents, and marketable securities, and total liabilities also decreased from **$20.62 million** to **$17.91 million**, while total stockholders' equity decreased from **$78.91 million** to **$65.49 million**, largely influenced by the accumulated deficit Consolidated Balance Sheets (as of December 31) | ASSETS | 2021 (USD) | 2020 (USD) | |:---|:---|:---|\n| Cash and cash equivalents | $64,370,800 | $74,866,133 | | Marketable securities | — | $10,002,550 | | Accounts receivable | $3,142,527 | $1,417,482 | | Prepaid expenses and other current assets | $954,792 | $1,241,239 | | Total current assets | $68,468,119 | $87,527,404 | | Property and equipment, net | $2,111,949 | $2,108,024 | | Operating lease right-of-use assets | $9,809,876 | $6,774,229 | | Deposits | $2,720,991 | $2,572,476 | | Restricted cash | $150,000 | $150,000 | | Other long term assets | $140,000 | $401,667 | | **Total assets** | **$83,400,935** | **$99,533,800** | | LIABILITIES AND STOCKHOLDERS' EQUITY | | | | Accounts payable | $2,590,701 | $2,070,303 | | Accrued expenses | $4,619,963 | $2,787,211 | | Research and development contract liability, current portion | $645,345 | $6,681,025 | | Operating lease liabilities, current portion | $4,931,675 | $4,777,427 | | Total current liabilities | $12,787,684 | $16,315,966 | | Research and development contract liability, net of current portion | — | $1,937,575 | | Operating lease liabilities, net of current portion | $5,121,179 | $2,368,787 | | **Total liabilities** | **$17,908,863** | **$20,622,328** | | Stockholders' equity: | | | | Common stock | $32,202 | $30,351 | | Additional paid-in capital | $262,906,084 | $232,159,029 | | Accumulated other comprehensive income | — | $7,131 | | Accumulated deficit | $(197,446,214) | $(153,285,039) | | **Total stockholders' equity** | **$65,492,072** | **$78,911,472** | | **Total liabilities and stockholders' equity** | **$83,400,935** | **$99,533,800** | - Total assets decreased from **$99.53 million** in 2020 to **$83.40 million** in 2021, primarily driven by a reduction in cash and marketable securities[617](index=617&type=chunk) - The accumulated deficit increased from **$(153.29) million** in 2020 to **$(197.45) million** in 2021, reflecting ongoing operating losses[617](index=617&type=chunk) [Consolidated Statements of Operat

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED SEPTEMBER 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO Commission file number: 001-38327 Cue Biopharma, Inc. (Exact name of registrant as specified in its charter) Delaware 47-3324577 (State or other jurisd ...

Cue Biopharma, Inc. (NASDAQ:CUE) Q2 2021 Results Conference Call August 17, 2021 4:30 PM ET Company Participants Dr. George Zavoico - VP, IR & Corporate Development Dan Passeri - Chief Executive Officer Dr. Anish Suri - President & Chief Scientific Officer Dr. Ken Pienta - Acting Chief Medical Officer Dr. Matteo Levisetti - SVP, Clinical Development Kerri-Ann Millar - Chief Financial Officer Conference Call Participants Mark Breidenbach - Oppenheimer Stephen Wiley - Stifel Tom Shrader - BTIG Brian Skorney - ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 Securities registered pursuant to Section 12(b) of the Act: Title of each class Trading Symbol(s) Name of each exchange on which registered Common Stock, par value $0.001 per share CUE Nasdaq Capital Market FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE QUARTERLY PERIOD ENDED JUNE 30, 2021 or ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCH ...

Financial Data and Key Metrics Changes - The company reported collaboration revenue of approximately $1.6 million for Q1 2021, up from $0.9 million in Q1 2020, primarily due to the extension of the Merck research program [59] - Research and development expenses decreased slightly to $9.8 million in Q1 2021 from $9.9 million in Q1 2020, attributed to lower laboratory costs and travel-related expenses [60] - General and administrative expenses increased to $4.3 million in Q1 2021 from $4 million in Q1 2020, mainly due to stock-based compensation and legal fees [61] - The company ended the quarter with approximately $73.3 million in cash, cash equivalents, and marketable securities, and working capital of approximately $60.8 million [62] Business Line Data and Key Metrics Changes - The lead drug candidate CUE-101 is currently in a Phase 1 monotherapy clinical trial for HPV positive recurrent or metastatic head and neck squamous cell carcinoma, with a confirmed partial response reported in a heavily pretreated patient [12][13] - The company is also developing CUE-102, targeting Wilms' Tumor 1 protein, in collaboration with LG Chem [18] Market Data and Key Metrics Changes - The company aims to expand patient reach and address resistance mechanisms through the development of Neo-STAT and redirected Immuno-STAT (RDI-STAT) platforms [19][32] Company Strategy and Development Direction - The company focuses on demonstrating the transformative nature of its protein engineering approach to provide breakthrough immunotherapies [21] - The strategy includes pursuing a registration path for CUE-101 as a monotherapy and exploring combination therapies with pembrolizumab [64][65] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical activity of CUE-101, highlighting its potential as a single-agent therapeutic for challenging patient populations [63] - The company anticipates several important milestones throughout the year, including the selection of a recommended Phase 2 dose for CUE-101 and updates on combination studies [64] Other Important Information - The company is collaborating with Merck on antigen-specific approaches for autoimmune diseases, with significant progress reported [38][90] - The Immuno-STAT platform is designed to selectively activate tumor-specific T cells while minimizing systemic activation of non-tumor related T cells [23][25] Q&A Session Summary Question: Can you provide details on the responding patient and their treatment history? - The patient had previously failed pembrolizumab and is still on study, with a confirmed partial response observed 12 weeks into treatment [77][78] Question: What metrics will drive the decision for the recommended Phase 2 dose? - The decision will be based on the totality of pharmacokinetic, pharmacodynamic, clinical response, and safety data [86] Question: How is the company prioritizing its pipeline opportunities? - The focus is on establishing a foothold with CUE-101 while also expanding into CUE-102 and other programs based on resource allocation [99][100]