IO Biotech(IOBT) - 2022 Q4 - Annual Report

Part I Item 1. Business IO Biotech is a clinical-stage biopharmaceutical company developing novel immune-modulating cancer vaccines, with lead candidate IO102-IO103 in Phase 3 for advanced melanoma - IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulating cancer vaccines based on its T-win technology platform[17] - The lead product candidate, IO102-IO103, targets immunosuppressive mechanisms mediated by IDO and PD-L1, demonstrating meaningful tumor regression and durable antitumor response in a Phase 1/2 trial for metastatic melanoma[17] - IO102-IO103, in combination with pembrolizumab, was granted Breakthrough Therapy Designation (BTD) by the FDA for unresectable/metastatic melanoma[17][23] - A potentially registrational Phase 3 trial (IOB-013/KN-D18) for IO102-IO103 in combination with pembrolizumab for first-line advanced melanoma began in May 2022, with 75% patient enrollment expected by mid-2023 and completion by year-end 2023[18] Overview The T-win platform activates T cells against immunosuppressive mechanisms, with a dual action of direct killing and tumor microenvironment modulation, featuring IO102-IO103 and IO112 in its pipeline - The T-win platform activates pre-existing T cells to target immunosuppressive mechanisms, with a dual mechanism of action: direct killing of immunosuppressive cells (tumor and TME cells expressing IDO/PD-L1) and modulation of the TME into a pro-inflammatory environment[19][44] - The lead candidate, IO102-IO103, combines IO102 (targeting IDO+) and IO103 (targeting PD-L1+) for a synergistic therapeutic effect[22] - IO112, a novel product candidate, targets Arginase 1, an immunoregulatory enzyme overexpressed in difficult-to-treat tumors, and is currently in a Phase 1 trial with an IND filing planned for 2023[28][32] Our Strategy IO Biotech's strategy focuses on advancing IO102-IO103 towards approval in advanced melanoma, expanding its clinical development into other solid tumors, and leveraging the T-win platform for new vaccine candidates - Advance IO102-IO103 towards approval in combination with anti-PD-1 therapy for first-line advanced melanoma, aiming for accelerated approval based on interim ORR analysis and MAA filing with EMA based on PFS[32] - Broaden IO102-IO103 clinical development into other solid tumor settings (NSCLC, SCCHN, UBC) through Phase 2 basket trials (IOB-022 for metastatic, IOB-032 for neo-adjuvant/adjuvant)[32] - Leverage the T-win platform to design and advance a portfolio of novel immune-modulating cancer vaccine candidates, including IO112 (targeting Arginase 1) and other preclinical compounds like TGFB[32][33] - Strengthen position through continuous innovation, intellectual property expansion (17 patent families), and selective strategic collaborations (e.g., with Merck for Keytruda supply)[36] Our Approach to Therapeutic Cancer Vaccines The T-win platform is a novel cancer vaccine approach activating T cells against immunosuppressive mechanisms, aiming for dual action, durable responses, and broad applicability - The T-win platform activates naturally occurring T cells to target immunosuppressive mechanisms, employing a dual mechanism: direct killing of immunosuppressive cells (IDO+, PD-L1+ tumor and TME cells) and modulation of the TME into a pro-inflammatory, anti-tumor environment[44][48] - Key advantages of the T-win platform include durability of response (targeting genetically stable immunosuppressive cells), dual/multi-epitope design for broader patient reach, favorable tolerability (subcutaneously injected peptides), versatility in combination therapies, well-understood manufacturing, and ease of administration[52] - The platform is built on the discovery of naturally occurring, pro-inflammatory T cells against immunosuppressive proteins like IDO and PD-L1 in cancer patients[45] Current Trials IO Biotech is conducting a Phase 3 registrational trial for IO102-IO103 in advanced melanoma and a Phase 2 basket trial for other solid tumors, showing encouraging initial data - The IOB-013/KN-D18 Phase 3 trial for IO102-IO103 + pembrolizumab in first-line advanced melanoma aims for 300 patients, with an interim ORR analysis one year after 75% randomization and PFS as the primary endpoint[53] - The IOB-022 Phase 2 basket trial is investigating IO102-IO103 + pembrolizumab in first-line metastatic NSCLC (PD-L1 ≥50%), SCCHN (CPS ≥20), and UBC (CPS ≥10)[54][55][56] - Initial data from 10 NSCLC patients in IOB-022 showed 4 partial responses and 4 stable diseases among 9 evaluable patients, with a safety profile consistent with prior experience[58] Our Product Candidates IO Biotech's pipeline features lead candidate IO102-IO103 in Phase 3 for melanoma and Phase 2 for other solid tumors, with IO112 targeting Arginase 1 and preclinical compounds exploring other immunosuppressive molecules - IO102-IO103, combining IDO-derived peptide IO102 and PD-L1-derived peptide IO103, is designed for synergistic anti-tumor effects by directly killing immunosuppressive cells and reducing TME immunosuppression[61][62] MM1636 Phase 1/2 Trial Results (Metastatic Melanoma, as of Jan 5, 2023) | Metric | Value | | :--- | :--- | | Median Follow-up | 49.8 months | | Evaluable Patients | 30 | | Confirmed ORR | 73.3% (95% CI: 54.1% to 87.7%) | | Complete Response Rate (CRR) | 50.0% (95% CI: 31.3% to 68.7%) | | Partial Response Rate | 23.3% (95% CI: 9.9% to 42.3%) | | Median PFS | 25.5 months | | Median OS | Not reached | | Treatment-related AE discontinuation rate | 17% | | Grade 3-5 AEs | 17% (5 patients) | - IO112, targeting Arginase 1, is in a first-in-human Phase 1 trial for arginase-positive solid tumors, with preclinical data showing enhanced anti-tumor effect in combination with anti-PD-1 antibody[169][172][174] - Preclinical development includes evaluating additional targets like TGF-ß (IO170) to modulate the TME for therapeutic benefit across various cancers[176] Collaborations IO Biotech maintains strategic collaborations with Herlev University Hospital for intellectual property and research, and with MSD International GmbH (Merck) for clinical trials, retaining global commercial rights to its compounds - Agreements with Herlev University Hospital grant IO Biotech options to acquire intellectual property rights related to T-cell activating inventions and non-exclusive licenses for clinical data[178][181] - IO Biotech has multiple Clinical Trial Collaboration and Supply Agreements with MSD (Merck) to evaluate IO102-IO103 in combination with KEYTRUDA® (pembrolizumab) for advanced melanoma (Phase 3), metastatic NSCLC, SCCHN, UBC (Phase 2), and neo-adjuvant/adjuvant melanoma and SCCHN (Phase 2)[188][189][191] - Under MSD collaborations, IO Biotech sponsors the trials, MSD provides KEYTRUDA® free of charge, data rights are shared, and IO Biotech maintains global commercial rights to its compounds[188][191] - A Clinical Trial Research Agreement with Cliniques Universitaires Saint-Luc supports an investigator-initiated study of peptide-based immunotherapy in SCCHN, with Saint-Luc owning data but granting IO Biotech an exclusive license and patent rights[201][202] Competition The biopharmaceutical industry, particularly immuno-oncology, is highly competitive, with IO Biotech facing established players possessing greater resources and market positions - The biopharmaceutical industry is intensely competitive, with major pharmaceutical and biotechnology companies, academic institutions, and government agencies conducting research and development in cancer immunotherapies[204] - Key competitors in immuno-oncology include Amgen, AstraZeneca, BMS, Merck, Novartis, Pfizer, and Roche[206][497] - In melanoma, dominant market players are BMS (nivolumab, nivolumab & ipilimumab) and Merck (pembrolizumab)[207][497] - Many competitors have significantly greater financial, technical, and human resources, potentially leading to faster product development, regulatory approval, and market commercialization[209][498] Manufacturing and Supply IO Biotech relies entirely on third-party CDMOs for manufacturing its peptide-based product candidates, leveraging well-understood synthetic chemistry for high-quality, low-cost, and easily administered products - IO Biotech's compounds are linear peptides manufactured through a well-understood solid-state peptide synthesis process, designed for long shelf-life and easy subcutaneous administration[214] - The company does not own or operate manufacturing facilities and relies on third-party CDMOs for all preclinical, clinical, and future commercial supply, ensuring compliance with regulatory requirements[215][217] - This outsourcing strategy allows the company to maintain an efficient infrastructure and focus internal expertise and resources on product candidate development and third-party management[216] Commercialization IO Biotech holds worldwide commercial rights to its immuno-oncology programs and plans to build a focused sales and marketing organization, potentially pursuing third-party distribution arrangements - IO Biotech holds worldwide development and commercial rights to its pipeline and intends to commercialize approved product candidates in key geographies[219] - The company currently lacks internal marketing, sales, or distribution capabilities[219] - Plans include building a focused sales and marketing organization to target oncologists and potentially entering into distribution and marketing arrangements with third parties[220][221] Intellectual Property IO Biotech protects its T-win platform and product candidates through 17 patent families covering various targets, trade secrets, and confidentiality agreements, with patents generally having a 20-year term - IO Biotech's intellectual property strategy involves seeking, maintaining, and defending patent rights, relying on trade secrets and know-how, and leveraging data exclusivity and market exclusivity[223] - The patent portfolio comprises 17 separate patent families, covering IO102 (IDO), IO103 (PD-L1), IO112 (Arginase 1), and other targets like TDO, PD-L2, CCL22, Arginase 2, and TGFbeta[224][225][226][227] - Patents generally have a 20-year term from their application filing date, with some U.S. patents having term adjustments[225] - The company holds the 'T-win' trademark in the EU, US, China, Japan, and UK, registered for pharmaceuticals and scientific/medical research services[228] Government Regulation The development and commercialization of IO Biotech's biological products are extensively regulated by authorities like the FDA and EMA, involving rigorous trials, complex approval processes, and ongoing post-approval obligations - Biological products are extensively regulated by the FDA in the U.S. and comparable authorities globally, covering research, development, testing, manufacturing, approval, marketing, and post-approval monitoring[229][230] - The U.S. approval process involves nonclinical testing (GLP), IND submission, clinical trials (Phases 1-3 under GCP), BLA submission, FDA review, manufacturing facility inspections (cGMP), and potential advisory committee review[231][232][233][234] - Expedited programs like Fast Track, Breakthrough Therapy Designation (BTD), Priority Review, and Accelerated Approval are available for serious conditions with unmet needs, but do not guarantee faster or ultimate approval[258][264] - Post-approval, products are subject to ongoing requirements including recordkeeping, adverse event reporting, compliance with promotion/advertising rules, and potential post-market studies or Risk Evaluation and Mitigation Strategies (REMS)[265][266][267] - In the EU, a centralized procedure for MA is mandatory for biotechnology-derived products, involving EMA evaluation (210 days, excluding clock stops) and European Commission approval; Orphan drug designation grants 10 years of market exclusivity[313][316][324] - The company's operations are subject to various healthcare laws (Anti-Kickback Statute, False Claims Act, HIPAA, Physician Payments Sunshine Act) and regulations concerning pricing and reimbursement, which vary significantly by country and can impact market access and profitability[275][280][289][333] Item 1A. Risk Factors IO Biotech faces numerous significant risks, including a limited operating history with consistent net losses, the need for substantial additional funding, unpredictable clinical trial outcomes, and intense competition - IO Biotech has a limited operating history, has incurred net losses since inception ($71.5 million in 2022, $67.9 million in 2021), and anticipates continued significant losses, with no guarantee of profitability or revenue generation from product sales[346][646] - The company will need substantial additional funding beyond its current $142.6 million cash and cash equivalents (sufficient through Q3 2024) to complete development and commercialization of product candidates, with potential for dilution or relinquishing rights if capital is raised through equity, debt, or collaborations[348][349][352][648] - All product candidates are in early clinical or preclinical development, and success is uncertain due to the high risk of clinical trial failure, the novel nature of T-win technology, and potential delays in site activation or patient enrollment[354][355][358][359][364][365] - The company relies on third parties for clinical trials and manufacturing, exposing it to risks of delays, increased costs, quality issues, and regulatory non-compliance[447][451][452] - The biopharmaceutical industry is highly competitive, with larger companies possessing greater resources, and the company's intellectual property protection (patents, trade secrets) faces challenges from infringement, invalidation, and evolving patent laws[495][498][529][530][535][537] - Operating as a public company incurs increased costs and management time for compliance (Sarbanes-Oxley Act, SEC, Nasdaq), and the stock price is subject to high volatility[598][577] Item 1B. Unresolved Staff Comments There are no unresolved staff comments from the SEC - No unresolved staff comments were reported[628] Item 2. Properties IO Biotech leases office and lab facilities in Copenhagen, New York, and Maryland, with leases expiring between 2027 and 2027, and believes its current facilities are adequate - IO Biotech leases approximately 622 square meters of office space and lab space in Copenhagen, Denmark, with leases expiring on December 31, 2027[629] - In the United States, the company leases office space in New York (lease expires February 28, 2027) and lab space in Maryland (lease expires March 31, 2027)[630] - A UK office facility lease in Monmouthshire is terminable at the company's convenience[630] - The company believes its current facilities are adequate and that suitable additional or substitute space will be available commercially as needed[631] Item 3. Legal Proceedings IO Biotech is not currently a party to any material legal proceedings, believing incidental litigation will not materially adversely affect its business, though litigation can still incur costs and divert resources - IO Biotech is not currently a party to any material legal proceedings[632] - The company believes that the final outcome of ordinary course litigation and claims will not have a material adverse effect on its business[632] - Litigation, regardless of outcome, can adversely impact the company due to defense and settlement costs and diversion of management resources[632] Item 4. Mine Safety Disclosures This item is not applicable to IO Biotech, Inc - Mine Safety Disclosures are not applicable to the Registrant[633] Part II Item 5. Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities IO Biotech's common stock is listed on Nasdaq under "IOBT," with no dividends paid or anticipated, and the company completed its IPO in November 2021, raising $103.3 million in net proceeds - IO Biotech's common stock is listed on the Nasdaq Global Select Market under the symbol "IOBT"[635] - The company has never declared or paid dividends on its common stock and anticipates retaining future earnings for business development[635][812] Common Stock and Equity Compensation Data (as of March 9, 2023 / Dec 31, 2022) | Metric | Value | | :--- | :--- | | Common Stock Outstanding (March 9, 2023) | 28,815,267 shares | | Holders of Record (March 9, 2023) | 12 | | Securities to be Issued Upon Exercise of Outstanding Options and Warrants (Dec 31, 2022) | 3,920,000 (approx) | | Weighted Average Exercise Price of Outstanding Options and Warrants (Dec 31, 2022) | $10.77 | | Remaining Available for Issuance Under Equity Compensation Plans (Dec 31, 2022) | 1,389,000 (approx) | - The company completed its IPO on November 9, 2021, issuing 8,222,500 shares of common stock and raising approximately $103.3 million in net proceeds[638][639] - There has been no material change in the planned use of IPO proceeds, and no equity securities were purchased by the issuer or affiliated parties[640][641] Item 6. (Reserved) This item is reserved and contains no information Item 7. Management's Discussion and Analysis of Financial Condition and Results of Operations IO Biotech, a clinical-stage biopharmaceutical company, has incurred significant operating losses, with net losses of $71.5 million in 2022 and $67.9 million in 2021, and anticipates needing additional funding beyond Q3 2024 - IO Biotech is a clinical-stage biopharmaceutical company focused on developing novel, immune-modulating cancer vaccines, with its lead candidate IO102-IO103 in a potentially registrational Phase 3 trial for advanced melanoma[644][645] Key Financial Highlights (Years Ended December 31) | Metric | 2022 (in thousands) | 2021 (in thousands) | Change (Amount) | Change (Percent) | | :--- | :--- | :--- | :--- | :--- | | Research and development expenses | $46,986 | $30,152 | $16,834 | 55.8% | | General and administrative expenses | $24,438 | $11,082 | $13,356 | 120.5% | | Total operating expenses | $71,424 | $41,234 | $30,190 | 73.2% | | Loss from operations | $(71,424) | $(41,234) | $(30,190) | 73.2% | | Other income (expense), net | $1,239 | $(26,577) | $27,816 | (104.7)% | | Net loss before income tax expense | $(70,185) | $(67,811) | $(2,374) | 3.5% | | Net loss | $(71,458) | $(67,879) | $(3,579) | 5.3% | | Cash and cash equivalents (as of Dec 31) | $142,590 | $211,531 | $(68,941) | (32.6)% | | Accumulated deficit (as of Dec 31) | $177,739 | $106,281 | $71,458 | 67.2% | - The increase in R&D expenses in 2022 was primarily driven by increased preclinical studies and clinical trial activities for IO102-IO103, including the Phase 3 trial, and higher personnel costs[668] - General and administrative expenses increased significantly in 2022 due to higher personnel costs (headcount and recruiting), insurance premiums, consulting, and travel costs[669][670] - The company's existing cash and cash equivalents ($142.6 million as of December 31, 2022) are expected to fund operations through the third quarter of 2024, but additional funding will be necessary thereafter[648][673][680] Overview IO Biotech is a clinical-stage biopharmaceutical company developing immune-modulating cancer vaccines, with its lead candidate IO102-IO103 in a Phase 3 trial for advanced melanoma, incurring significant net losses and requiring future capital raises - IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulating cancer vaccines based on its T-win technology platform[644] - The lead product candidate, IO102-IO103, has Breakthrough Therapy Designation for unresectable/metastatic melanoma and is in a potentially registrational Phase 3 trial[644][645] Net Loss and Cash Position (Years Ended December 31) | Metric | 2022 (in millions) | 2021 (in millions) | | :--- | :--- | :--- | | Net Loss | $(71.5) | $(67.9) | | Accumulated Deficit | $(177.7) | $(106.2) | | Cash and Cash Equivalents | $142.6 | $211.5 | - Current cash and cash equivalents ($142.6 million as of Dec 31, 2022) are estimated to fund operations through Q3 2024, with additional funding required thereafter[648] Components of Operating Results Operating expenses primarily comprise research and development (R&D) and general and administrative (G&A) costs, with R&D expenses reduced by grant income and tax credits, and other income/expense reflecting foreign exchange and interest - Research and development expenses include personnel, consultants, CROs, CMOs, lab expenses, and patent-related costs, all expensed as incurred[652] - R&D expenses are reduced by grant income (e.g., $0.03 million in 2022, $0.1 million in 2021) and Danish tax credits ($0.8 million in both 2022 and 2021)[654][655][754][755] - General and administrative expenses primarily cover personnel, professional services (legal, audit, accounting), and facility-related fees[663] - Other income (expense), net, is composed of foreign exchange gains/losses, interest income/expense, and, in 2021, fair value adjustments on convertible notes[665] Results of Operations In 2022, total operating expenses increased by 73.2% to $71.4 million, driven by significant increases in R&D and G&A expenses, while other income (expense), net, shifted to a net income due to the absence of preferred stock tranche adjustments Operating Expenses and Other Income (Years Ended December 31) | Metric | 2022 (in thousands) | 2021 (in thousands) | Change (Amount) | Change (Percent) | | :--- | :--- | :--- | :--- | :--- | | Research and Development Expenses | $46,986 | $30,152 | $16,834 | 55.8% | | General and Administrative Expenses | $24,438 | $11,082 | $13,356 | 120.5% | | Other Income (Expense), Net | $1,239 | $(26,577) | $27,816 | (104.7)% | - The $16.8 million increase in R&D expenses was primarily due to a $5.3 million increase in preclinical studies and clinical trial-related activities for IO102-IO103 (including Phase 3), a $7.7 million increase in personnel costs, and a $2.9 million increase in chemistry, manufacturing, and control activities[668] - The $13.4 million increase in G&A expenses was mainly driven by a $4.3 million increase in personnel costs (headcount and recruiting) and a $7.9 million increase in consultants and other costs (including $2.9 million insurance, $2.3 million consulting, $0.8 million travel)[669][670] - The shift in Other income (expense), net, from a net expense to a net income was primarily due to the decrease in fair value adjustments on the company's preferred stock tranche obligations, which were settled in 2021[671] Liquidity and Capital Resources IO Biotech's operations are financed by past equity issuances, including a 2021 IPO, with $142.6 million in cash as of December 31, 2022, projected to fund operations through Q3 2024, necessitating additional future financing - Operations have been financed by $288.7 million in net proceeds from convertible preference shares, convertible notes, ordinary shares, and a 2021 IPO ($103.3 million net proceeds)[646][672] Cash Flow Summary (Years Ended December 31) | Cash Flow Activity | 2022 (in thousands) | 2021 (in thousands) | | :--- | :--- | :--- | | Net cash used in operating activities | $(59,729) | $(40,646) | | Net cash used in investing activities | $(690) | $(153) | | Net cash provided by financing activities | $0 | $252,951 | - Cash used in operating activities increased from $40.6 million in 2021 to $59.7 million in 2022, primarily due to higher net losses and changes in working capital[675][676] - The company's $142.6 million in cash and cash equivalents (as of Dec 31, 2022) is expected to fund operations through Q3 2024, but additional financing will be required for future clinical and preclinical activities[673][680] Contractual Obligations and Commitments IO Biotech has lease obligations for its office and lab spaces extending to 2027 and enters into various third-party service contracts, which are generally terminable with short notice, with non-cancelable obligations not considered material - IO Biotech has lease agreements for office space in Copenhagen, Denmark (expires Dec 2027), Rockville, Maryland (expires April 2027), and New York, NY (expires Jan 2027)[683] - The company enters into contracts with third-party service providers for clinical trials, preclinical research, manufacturing, and other services, which typically include termination clauses of 30 to 90 days[684] - Non-cancelable obligations under these service agreements are not considered material, but financial obligations for active clinical trial patients may extend beyond contractual termination notice periods[684] Critical Accounting Policies and Significant Judgments and Estimates IO Biotech's financial statements require significant estimates for R&D accruals, equity-based compensation, and income taxes, with a full valuation allowance against deferred tax assets due to historical losses - Key areas requiring significant estimates and assumptions include contract research organization (CRO) accruals, fair value of stock-based compensation awards, and valuation of deferred tax assets[686][689] - The company's going concern evaluation projects existing cash and cash equivalents ($142.6 million as of Dec 31, 2022) to fund operations through Q3 2024[688] - Research and development costs, particularly those from third-party service providers, are estimated based on work progress, contract milestones, patient enrollment, and study duration[689][691] - Equity-based compensation is measured at fair value using a Black-Scholes option pricing model, incorporating assumptions for volatility, expected term, risk-free interest rate, and dividend yield[694] - Deferred tax assets are recognized for temporary differences and loss carryforwards, but a full valuation allowance is recorded against net deferred tax assets in Denmark and the U.S. due to the unlikelihood of realization given historical operating losses[697][699][826] Item 7A. Quantitative and Qualitative Disclosures About Market Risk As a smaller reporting company, IO Biotech is not required to provide quantitative and qualitative disclosures about market risk - IO Biotech is a smaller reporting company and is not required to provide quantitative and qualitative disclosures about market risk[705] Item 8. Financial Statements and Supplementary Data This section presents IO Biotech's audited consolidated financial statements for 2022 and 2021, prepared under U.S. GAAP, highlighting continued net losses and increased operating expenses - The consolidated financial statements for the years ended December 31, 2022 and 2021 were audited by EY Godkendt Revisionspartnerselskab and present fairly the financial position and results of operations in conformity with U.S. GAAP[709] Consolidated Balance Sheet Highlights (as of December 31, in thousands) | Metric | 2022 | 2021 | | :--- | :--- | :--- | | Cash and cash equivalents | $142,590 | $211,531 | | Total current assets | $148,219 | $221,738 | | Total assets | $151,805 | $222,288 | | Total liabilities | $12,951 | $10,364 | | Total stockholders' equity | $138,854 | $211,924 | | Accumulated deficit | $(177,739) | $(106,281) | Consolidated Statements of Operations and Comprehensive Loss Highlights (Years Ended December 31, in thousands) | Metric | 2022 | 2021 | | :--- | :--- | :--- | | Research and development | $46,986 | $30,152 | | General and administrative | $24,438 | $11,082 | | Total operating expenses | $71,424 | $41,234 | | Net loss | $(71,458) | $(67,879) | | Net loss per common share, basic and diluted | $(2.48) | $(17.30) | Consolidated Statements of Cash Flows Highlights (Years Ended December 31, in thousands) | Cash Flow Activity | 2022 | 2021 | | :--- | :--- | :--- | | Net cash used in operating activities | $(59,729) | $(40,646) | | Net cash used in investing activities | $(690) | $(153) | | Net cash provided by financing activities | $0 | $252,951 | Notes to the Consolidated Financial Statements The notes detail IO Biotech's corporate reorganization, IPO, significant accounting policies, fair value measurements, collaboration agreements, and tax provisions, highlighting ongoing losses and future funding needs - IO Biotech completed a corporate reorganization in November 2021, making IO Biotech ApS a wholly-owned subsidiary, and subsequently completed an IPO, raising $103.3 million in net proceeds[728][729] - The company's financial statements are prepared in conformity with U.S. GAAP, with the Euro as the functional currency for its Danish and UK subsidiaries, and the U.S. dollar as the reporting currency[739][744] - As of December 31, 2022, cash and cash equivalents were $142.6 million, with an accumulated deficit of $177.7 million, and current cash is expected to fund operations through Q3 2024[736] - Key accounting estimates include contract research organization accruals, fair value of stock-based compensation (using Black-Scholes model), and valuation of deferred tax assets, for which a full valuation allowance is recorded[743][762][764][769][826] - The company has significant collaborations with MSD International GmbH for clinical trials of IO102-IO103 in combination with KEYTRUDA®, and with Herlev University Hospital for scientific support and intellectual property[787][789][790][791][792] - As of December 31, 2022, the company had net operating loss (NOL) carryforwards of approximately $140.5 million in Denmark, which can be carried forward indefinitely[827] Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure IO Biotech reported no changes in or disagreements with its accountants on accounting and financial disclosure - No changes in or disagreements with accountants on accounting and financial disclosure were reported[835] Item 9A. Controls and Procedures IO Biotech's management concluded that disclosure controls and internal control over financial reporting were effective as of December 31, 2022, having remediated a previously identified material weakness - Management concluded that IO Biotech's disclosure controls and procedures were effective as of December 31, 2022[838] - A previously disclosed material weakness in internal control over financial reporting (related to financial statement close process and lack of finance capacity/expertise) was remediated during 2022[840][841] - Remediation efforts included hiring a Chief Financial Officer and Chief Accounting Officer, four additional accounting/financial reporting personnel, and enhancing financial close processes with additional independent reviews and improved precision[841][842] - Management assessed and concluded that the company's internal control over financial reporting was effective as of December 31, 2022[846] - As an emerging growth company, IO Biotech is exempt from the requirement to include an attestation report of its independent registered public accounting firm on internal control over financial reporting[847] Item 9B. Other Information This item reports that there is no other information required to be disclosed - No other information is required to be disclosed under this item[848] Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections This item reports that there are no disclosures regarding foreign jurisdictions that prevent inspections - No disclosures regarding foreign jurisdictions that prevent inspections were reported[849] Part III Item 10. Directors, Executive Officers and Corporate Governance The information required for this item is incorporated by reference from the company's definitive proxy statement for its 2023 Annual Meeting of Stockholders - Information regarding Directors, Executive Officers and Corporate Governance is incorporated by reference from the company's definitive proxy statement for the 2023 Annual Meeting of Stockholders[852] Item 11. Executive Compensation The information required for this item is incorporated by reference from the company's definitive proxy statement for its 2023 Annual Meeting of Stockholders - Information regarding Executive Compensation is incorporated by reference from the company's definitive proxy statement for the 2023 Annual Meeting of Stockholders[853] Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters The information required for this item is incorporated by reference from the company's definitive proxy statement for its 2023 Annual Meeting of Stockholders - Information regarding Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters is incorporated by reference from the company's definitive proxy statement for the 2023 Annual Meeting of Stockholders[854] Item 13. Certain Relationships and Related Transactions, and Director Independence The information required for this item is incorporated by reference from the company's definitive proxy statement for its 2023 Annual Meeting of Stockholders - Information regarding Certain Relationships and Related Transactions, and Director Independence is incorporated by reference from the company's definitive proxy statement for the 2023 Annual Meeting of Stockholders[855] Item 14. Principal Accounting Fees and Services The information required for this item is incorporated by reference from the company's definitive proxy statement for its 2023 Annual Meeting of Stockholders - Information regarding Principal Accounting Fees and Services is incorporated by reference from the company's definitive proxy statement for the 2023 Annual Meeting of Stockholders[856] Part IV Item 15. Exhibits, Financial Statement Schedules This section lists all exhibits and financial statement schedules filed as part of the Form 10-K, including corporate documents and key collaboration agreements, with schedules omitted as information is in the financial statements - This item lists exhibits, including Amended and Restated Certificate of Incorporation and Bylaws, Indemnification Agreements, 2021 Equity and Incentive Plan, and 2021 Employee Stock Purchase Plan[858] - Key agreements listed include Option Assignment Agreements and a Framework Assignment Agreement with Herlev Hospital, and Clinical Trial Collaboration and Supply Agreements with MSD International GmbH[858][859] - Financial statement schedules have been omitted because they are either not required or the information is included in the consolidated financial statements or their notes[858] Item 16. Form 10-K Summary This item indicates that no Form 10-K Summary is provided - No Form 10-K Summary is provided[861]