A wave of after-hours activity swept through select biotech and medical device names Thursday, with several micro- and mid-cap stocks posting sharp gains following session-end catalysts, volume spikes, or pipeline updates. Below are key price moves and developments from RVPH, PEN, PALI, IOBT, RLYB, and VOR.Reviva Pharmaceuticals Holdings Inc. (RVPH) extended its explosive rally into after-hours trading Thursday, jumping 18.27% to $0.58 following a 35.1% surge during the regular session. The move came on a ...

Company Performance - MoonLake Immunotherapeutics (NASDAQ:MLTX) experiences a drastic decrease in its stock price to $6.24, about 89.93% [1][6] - KALA BIO, Inc. (NASDAQ:KALA) sees its stock decline sharply to $2.13, translating to an 88.82% decrease [2][6] - IO Biotech, Inc. (NASDAQ:IOBT) experiences a 77.31% decrease in its stock price, falling to $0.35 [3][6] - Maris-Tech Ltd. (NASDAQ:MTEKW) sees its stock price decrease to $0.22, a 71.16% drop [4] Industry Insights - The recent market movements highlight the volatile nature of the stock market, where companies across various sectors can experience significant fluctuations [5] - Factors such as market sentiment, industry trends, and company-specific developments play crucial roles in influencing stock prices [5]

Core Viewpoint - IO Biotech's Cylembio (imsapepimut and etimupepimut) will not proceed with a Biologics License Application (BLA) based on the current clinical trial data, as recommended by the FDA, despite showing improved progression-free survival (PFS) in the IOB-013 trial [1][6] Regulatory Update - The FDA advised against submitting a BLA for Cylembio based on IOB-013 trial data, which narrowly missed statistical significance for PFS [1][6] - IO Biotech plans to engage in further discussions with the FDA to design a new registrational study for Cylembio [2][6] Clinical Trials - Cylembio is currently being evaluated in multiple clinical trials, including a pivotal Phase 3 trial (IOB-013/KN-D18) in combination with Merck's KEYTRUDA (pembrolizumab) for advanced melanoma [3][5] - The IOB-013 trial enrolled 407 patients across over 100 centers globally, with topline results reported in Q3 2025 [5][7] Financial and Operational Strategy - The company is implementing a restructuring plan to conserve capital, which includes a workforce reduction of approximately 50% and expects a non-recurring charge of $1.0 - $1.5 million in Q3 2025 [2][6] - IO Biotech has sufficient capital to sustain operations into Q1 2026 while pursuing regulatory approval for Cylembio [2] Company Overview - IO Biotech is a clinical-stage biopharmaceutical company focused on developing immune-modulatory, off-the-shelf therapeutic cancer vaccines using its T-win platform [8]

Core Insights - IO Biotech is set to present significant findings from its clinical trials at the 2025 ESMO Congress in Berlin, focusing on its cancer vaccine candidates [1][2][5] Group 1: Clinical Trials and Presentations - The company will present results from a randomized Phase 3 trial of the IO102-IO103 cancer vaccine in combination with pembrolizumab for first-line advanced melanoma [2][5] - A poster session will feature final data from a Phase 2 basket trial assessing the same vaccine in combination with pembrolizumab for various advanced solid tumors [3][5] - The pivotal Phase 3 trial (IOB-013/KN-D18) enrolled 407 patients across over 100 centers globally, with the primary endpoint being progression-free survival [8] Group 2: Vaccine Development and Mechanism - Cylembio, the lead candidate, is designed to target both tumor cells and immune-suppressive cells in the tumor microenvironment by activating T cells against IDO1 and PD-L1 positive cells [4][10] - The company is conducting multiple trials, including a Phase 2 basket trial for non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN) [9][10] Group 3: Company Overview - IO Biotech is a clinical-stage biopharmaceutical company headquartered in Copenhagen, Denmark, with a focus on developing immune-modulatory cancer vaccines [10]

Summary of IO Biotech FY Conference Call Company Overview - **Company**: IO Biotech (NasdaqGS: IOBT) - **Focus**: Development of SilentBio™, an immune modulatory cancer vaccine targeting advanced melanoma and other cancers Key Industry Insights - **Market Opportunity**: The market for first-line advanced melanoma is significant, with 15,000 new diagnoses annually in the US and a growth rate of 9% per year, representing a billion-dollar opportunity [4][11] - **Unmet Need**: 50% of patients treated with current standard care do not benefit, highlighting the need for better treatment options [4][11] Core Product Insights - **SilentBio™**: - Combination of IO102 and IO103, showing promising results in clinical trials - Demonstrated a median progression-free survival (PFS) of 19.4 months compared to 11.0 months for the control group [3][7] - Hazard ratio of 0.77 and a p-value of 0.056, indicating a near statistical significance [3][7] - Improved PFS observed across all pre-specified subgroups without added systemic toxicity [3][9] Clinical Trial Results - **Phase 3 Trial**: - Conducted in over 100 centers globally with 407 patients enrolled [6][7] - Notable results include: - Median PFS of 24.8 months for patients without prior anti-PD-1 exposure [8] - Dramatic PFS improvement in PD-L1 negative patients, with 16.6 months versus 3 months in the control group [8] - Overall survival (OS) trends favoring the combination arm, with a hazard ratio of 0.79 [9][10] Regulatory and Market Readiness - **FDA Engagement**: - Preparing for a Biologics License Application (BLA) submission by the end of 2025 [4][16] - Discussions with the FDA are ongoing, with a meeting scheduled for Q3 2025 [4][20] - **Manufacturing and Distribution**: - Secured supply chain and commercial-scale manufacturing in place [5][11] Future Pipeline and Expansion - **Additional Trials**: - Two Phase 2 trials for SilentBio™ in lung and head and neck cancers are underway [13] - Plans to expand into earlier clinical stages and other indications [16][17] - **New Targets**: - Development of IO112 (arginase) and IO170 (TGF-beta) for broader indications [15][17] Financial Position - **Cash Reserves**: - Cash balance of $28 million as of Q2 2025, sufficient to fund operations into Q1 2026 [20] Conclusion - IO Biotech is positioned to potentially set a new standard in the treatment of advanced melanoma with SilentBio™, backed by promising clinical data and a robust pipeline for future growth [11][12]

Core Insights - The presentation is part of the Morgan Stanley Global Healthcare Conference, featuring IO Biotech's leadership team, including CEO Mai-Britt Zocca, CFO Amy Sullivan, and CMO Qasim Ahmad [1][2] Company Overview - IO Biotech is being introduced to the audience, indicating a focus on sharing their story and developments within the company [2]

Summary of IO Biotech Conference Call Company Overview - **Company**: IO Biotech - **Event**: Morgan Stanley Global Healthcare Conference - **Key Personnel**: Mai-Britt Zocca (CEO), Amy Sullivan (CFO), Qasim Ahmad (CMO) Core Points and Arguments - **Lead Program**: IO102-IO103, an immune-modulatory cancer vaccine targeting IDO and PD-L1 in first-line advanced melanoma [2][3] - **Clinical Results**: - Median Progression-Free Survival (PFS) of 19.4 months compared to 11 months in the control arm (pembrolizumab) [2][13] - Encouraging data across all subgroups and stratification markers [2][3] - No additional safety concerns in the experimental arm, indicating a favorable risk-benefit profile [3][19] - **Regulatory Plans**: - Plans to submit a Biologics License Application (BLA) by the end of the year [3][33] - Ongoing discussions with the FDA regarding the totality of evidence [22][21] - **Study Design**: - Phase III randomized study with 407 patients, focusing on first-line treatment [10] - Primary endpoint was PFS, with overall survival (OS) and overall response rate (ORR) as secondary endpoints [12] - **Comparative Analysis**: - Current standard treatments (nivolumab, Opdivo, pembrolizumab) show PFS ranging from 4.6 to 11.6 months [13] - IO Biotech's combination therapy shows a significant PFS benefit of 8.4 months over pembrolizumab alone [13] - **Subgroup Analysis**: - Significant benefits observed in PD-L1 negative patients (16.1 months vs. 3 months) with a P-value of 0.006 [17] - Consistent benefits across various prognostic factors [17][19] Additional Important Content - **Future Presentations**: Data will be presented at an upcoming congress as a late breaker [20] - **Cash Position**: - Ended Q2 with over $28 million in cash, with additional funding from a debt facility [51] - Sufficient capital to support operations until Q1 2026, but plans to raise more for commercialization [51] - **Market Landscape**: - Monitoring the rise of biotech innovation in China but sees no immediate impact on strategy [52] - Interest in leveraging artificial intelligence in drug development, though not currently a focus [53][54] - **Regulatory Environment**: - Keeping a close eye on potential impacts from tariffs and regulatory changes [55] - **Focus Areas**: - Preparing for discussions with the FDA and planning for future presentations [57] - Considering filing a Marketing Authorization Application (MAA) post-FDA interactions [58] This summary encapsulates the key points discussed during the conference call, highlighting the company's advancements, clinical data, regulatory strategies, and market considerations.

Core Viewpoint - IO Biotech, Inc. (IOBT) has been upgraded to a Zacks Rank 2 (Buy), indicating a positive outlook on its earnings estimates, which is a significant factor influencing stock prices [1][3]. Earnings Estimates and Stock Price Movement - The Zacks rating system is based on the consensus measure of EPS estimates from sell-side analysts, reflecting the company's changing earnings picture [1][2]. - A strong correlation exists between changes in earnings estimates and near-term stock price movements, largely due to institutional investors adjusting their valuations based on these estimates [4][6]. Company Performance and Investor Sentiment - The upgrade for IO Biotech suggests an improvement in the company's underlying business, which could lead to increased buying pressure and a rise in stock price [5][10]. - Over the past three months, the Zacks Consensus Estimate for IO Biotech has increased by 1%, indicating a positive trend in earnings estimates [8]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a proven track record of performance, particularly for Zacks Rank 1 stocks, which have generated an average annual return of +25% since 1988 [7][9]. - IO Biotech's upgrade to Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, suggesting a strong potential for market-beating returns in the near term [10].

[FORM 10-Q Cover Page](index=1&type=section&id=FORM%2010-Q%20Cover%20Page) IO Biotech, Inc. filed its Quarterly Report on Form 10-Q for the period ended June 30, 2025. The company is a **non-accelerated filer**, **smaller reporting company**, and an **emerging growth company**[2](index=2&type=chunk)[3](index=3&type=chunk)[5](index=5&type=chunk) Registrant Information | Attribute | Value | | :--- | :--- | | Exact Name of Registrant | IO Biotech, Inc. | | State of Incorporation | Delaware | | IRS Employer Identification No. | 87-0909276 | | Principal Executive Offices | Ole Maaløes Vej 3, DK-2200 Copenhagen N, Denmark | | Telephone Number | +45 7070 2980 | | Title of Class | Common Stock, par value $0.001 per share | | Trading Symbol | IOBT | | Exchange Registered | The Nasdaq Stock Market LLC | | Shares Outstanding (as of Aug 11, 2025) | 65,880,914 | | Filer Status | Non-accelerated filer, Smaller reporting company, Emerging growth company | [Table of Contents](index=3&type=section&id=Table%20of%20Contents) [Cautionary Note Regarding Forward-Looking Statements](index=4&type=section&id=CAUTIONARY%20NOTE%20REGARDING%20FORWARD-LOOKING%20STATEMENTS) This report contains forward-looking statements regarding future operations, financial position, business strategy, and management objectives, subject to risks and uncertainties that could cause actual results to differ materially - Key factors that could cause actual results to differ include the timing and success of clinical trials (e.g., Cylembio, IO112, IO170), regulatory approvals, commercialization capabilities, manufacturing, intellectual property protection, and the ability to obtain additional financing[10](index=10&type=chunk)[14](index=14&type=chunk) [Trademarks](index=7&type=section&id=Trademarks) The report includes trademarks, service marks, and trade names owned by IO Biotech or other companies, noting that the omission of ® and ™ symbols does not waive their respective owners' rights[15](index=15&type=chunk) [PART I—FINANCIAL INFORMATION](index=8&type=section&id=PART%20I%E2%80%94FINANCIAL%20INFORMATION) [Item 1. Interim Financial Statements (Unaudited)](index=8&type=section&id=Item%201.%20Interim%20Financial%20Statements%20(Unaudited)) This section presents the unaudited interim consolidated financial statements, including balance sheets, statements of operations and comprehensive loss, stockholders' equity, and cash flows, along with detailed notes explaining the company's business, accounting policies, fair value measurements, and specific financial line items [Consolidated Balance Sheets](index=8&type=section&id=Consolidated%20Balance%20Sheets) Consolidated Balance Sheet Highlights (in thousands) | Metric | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Cash and cash equivalents | $28,131 | $60,031 | | Total current assets | $38,980 | $64,951 | | Total assets | $42,326 | $67,699 | | Total current liabilities | $19,897 | $19,486 | | Term loan debt, net | $6,720 | — | | Common stock warrants (non-current) | $13,249 | — | | Total liabilities | $40,734 | $20,684 | | Total stockholders' equity | $1,592 | $47,015 | - Total assets decreased from **$67.7 million** at December 31, 2024, to **$42.3 million** at June 30, 2025, primarily due to a significant reduction in cash and cash equivalents[18](index=18&type=chunk) - Total liabilities increased substantially from **$20.7 million** to **$40.7 million**, driven by the introduction of term loan debt and common stock warrants[18](index=18&type=chunk) [Consolidated Statements of Operations and Comprehensive Loss](index=9&type=section&id=Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) Consolidated Statements of Operations and Comprehensive Loss Highlights (in thousands) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development expenses | $16,652 | $15,848 | $33,027 | $30,159 | | General and administrative expenses | $6,518 | $5,685 | $12,727 | $11,571 | | Total operating expenses | $23,170 | $21,533 | $45,754 | $41,730 | | Loss from operations | $(23,170) | $(21,533) | $(45,754) | $(41,730) | | Total other (expense) income, net | $(2,929) | $1,221 | $(2,620) | $2,376 | | Net loss | $(26,217) | $(20,686) | $(48,638) | $(40,143) | | Net loss per common share, basic and diluted | $(0.40) | $(0.31) | $(0.74) | $(0.61) | - Net loss increased by **26.7%** to **$26.2 million** for the three months ended June 30, 2025, compared to **$20.7 million** in the prior year, primarily due to a significant decrease in other income (expense), net[21](index=21&type=chunk) - For the six months ended June 30, 2025, net loss increased by **21.2%** to **$48.6 million**, compared to **$40.1 million** in the prior year, driven by higher operating expenses and a negative shift in other income (expense)[21](index=21&type=chunk) [Consolidated Statements of Stockholders' Equity](index=10&type=section&id=Consolidated%20Statements%20of%20Stockholders%27%20Equity) Consolidated Statements of Stockholders' Equity Highlights (in thousands) | Metric | Balance, January 1, 2025 | Balance, June 30, 2025 | | :--- | :--- | :--- | | Common Stock (shares) | 65,880,914 | 65,880,914 | | Common Stock (amount) | $66 | $66 | | Additional Paid-In Capital | $413,113 | $416,289 | | Accumulated Other Comprehensive Loss | $(6,851) | $(6,812) | | Accumulated Deficit | $(359,313) | $(407,951) | | Total Stockholders' Equity | $47,015 | $1,592 | - Total stockholders' equity significantly decreased from **$47.0 million** at January 1, 2025, to **$1.6 million** at June 30, 2025, primarily due to the net loss incurred during the period[24](index=24&type=chunk) - The accumulated deficit increased by **$48.6 million** to **$408.0 million** as of June 30, 2025, reflecting ongoing operating losses[24](index=24&type=chunk) [Consolidated Statements of Cash Flows](index=11&type=section&id=Consolidated%20Statements%20of%20Cash%20Flows) Consolidated Statements of Cash Flows Highlights (in thousands) | Metric | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(42,893) | $(41,914) | | Net cash used in investing activities | $(54) | $(23) | | Net cash provided by financing activities | $11,487 | — | | Net decrease in cash, cash equivalents and restricted cash | $(31,460) | $(41,937) | | Cash, cash equivalents and restricted cash, end of period | $28,399 | $101,015 | - Net cash used in operating activities increased slightly to **$42.9 million** for the six months ended June 30, 2025, compared to **$41.9 million** in the prior year[27](index=27&type=chunk) - Net cash provided by financing activities was **$11.5 million** for the six months ended June 30, 2025, primarily from the EIB Tranche A loan facility, compared to no financing activities in the prior year[27](index=27&type=chunk) - Cash, cash equivalents and restricted cash decreased significantly from **$101.0 million** at June 30, 2024, to **$28.4 million** at June 30, 2025[27](index=27&type=chunk) [Notes to Consolidated Financial Statements](index=12&type=section&id=Notes%20to%20Consolidated%20Financial%20Statements) [Note 1. Description of Business, Organization and Liquidity](index=12&type=section&id=Note%201.%20Description%20of%20Business%2C%20Organization%20and%20Liquidity) - IO Biotech, Inc. is a clinical-stage biopharmaceutical company focused on developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines based on its **T-win® platform**[30](index=30&type=chunk) - The company has incurred substantial losses since inception, with an accumulated deficit of **$408.0 million** as of June 30, 2025, and expects continued operating losses[43](index=43&type=chunk) - Management has concluded that there is **substantial doubt** about the company's ability to continue as a **going concern** for at least 12 months from the financial statement issuance date, citing insufficient cash and cash equivalents to fund operations beyond **Q1 2026**, even with the second tranche of the EIB Loan[43](index=43&type=chunk)[46](index=46&type=chunk) - The company plans to secure additional funding through equity or debt financings, strategic collaborations, or the draw down of remaining EIB loan tranches (Tranche C of **€15.0 million** is subject to unmet business conditions)[44](index=44&type=chunk)[45](index=45&type=chunk) [Note 2. Summary of Significant Accounting Policies](index=14&type=section&id=Note%202.%20Summary%20of%20Significant%20Accounting%20Policies) - The company classifies warrants issued with common stock or debt as either liability or equity based on **ASC 480-10** or **ASC 815-40**. Liability-classified warrants are measured at fair value through profit or loss[49](index=49&type=chunk)[51](index=51&type=chunk)[52](index=52&type=chunk) - The company adopted **ASU 2023-07 (Segment Reporting)** effective December 31, 2024, which enhances disclosures about significant segment expenses[55](index=55&type=chunk) - New accounting standards **ASU 2023-06 (Disclosure Improvements)**, **ASU 2023-09 (Income Tax Disclosures)**, and **ASU 2024-03 (Expense Disaggregation)** are being assessed for their impact on future financial statements[56](index=56&type=chunk)[57](index=57&type=chunk)[58](index=58&type=chunk) [Note 3. Fair Value Measurements](index=17&type=section&id=Note%203.%20Fair%20Value%20Measurements) Fair Value Measurements (in thousands) | Item | June 30, 2025 Total | June 30, 2025 Level 1 | June 30, 2025 Level 3 | | :--- | :--- | :--- | :--- | | Money market funds | $22,670 | $22,670 | — | | Common stock warrants | $13,249 | — | $13,249 | | Item | December 31, 2024 Total | December 31, 2024 Level 1 | | :--- | :--- | :--- | | Money market funds | $46,134 | $46,134 | - The company's common stock warrants (Tranche A and B) are classified as **Level 3 liabilities** and valued using the **Black-Scholes option-pricing model**, with a fair value of **$13.2 million** as of June 30, 2025[62](index=62&type=chunk)[63](index=63&type=chunk)[64](index=64&type=chunk)[66](index=66&type=chunk) - Money market funds are classified as **Level 1 assets**, totaling **$22.7 million** at June 30, 2025, down from **$46.1 million** at December 31, 2024[60](index=60&type=chunk)[61](index=61&type=chunk) [Note 4. License and Collaboration Agreements](index=18&type=section&id=Note%204.%20License%20and%20Collaboration%20Agreements) - IO Biotech has multiple clinical collaboration agreements with **MSD International GmbH** (an affiliate of Merck) to evaluate **IO102-IO103** in combination with **KEYTRUDA® (pembrolizumab)** for various cancer types[67](index=67&type=chunk)[68](index=68&type=chunk)[69](index=69&type=chunk)[70](index=70&type=chunk) - Under these collaborations, IO Biotech sponsors the clinical trials and bears most costs, while MSD provides **KEYTRUDA®** free of charge. Data rights are shared, and IO Biotech retains global commercial rights to **IO102-IO103**[67](index=67&type=chunk)[68](index=68&type=chunk)[69](index=69&type=chunk)[70](index=70&type=chunk) [Note 5. Prepaid Expenses and Other Current Assets](index=19&type=section&id=Note%205.%20Prepaid%20Expenses%20and%20Other%20Current%20Assets) Prepaid Expenses and Other Current Assets (in thousands) | Item | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Deferred financing asset | $5,657 | — | | Prepaid income taxes | $1,607 | $1,292 | | Prepaid contract research and development costs | $1,109 | $1,119 | | Research and development tax credit receivable | $865 | $573 | | Insurance | $639 | $768 | | Value-added tax refund receivable | $276 | $365 | | Other | $696 | $803 | | Total | $10,849 | $4,920 | - Total prepaid expenses and other current assets increased significantly from **$4.9 million** at December 31, 2024, to **$10.8 million** at June 30, 2025, primarily due to a new deferred financing asset of **$5.7 million**[71](index=71&type=chunk) [Note 6. Property and Equipment, Net](index=19&type=section&id=Note%206.%20Property%20and%20Equipment%2C%20Net) Property and Equipment, Net (in thousands) | Item | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Laboratory equipment | $927 | $839 | | Office furniture | $261 | $235 | | Computer hardware | $141 | $141 | | Less: accumulated depreciation | $(726) | $(577) | | Total | $603 | $638 | - Net property and equipment decreased slightly from **$638 thousand** at December 31, 2024, to **$603 thousand** at June 30, 2025, with **$0.1 million** in depreciation expense recognized for both the three and six months ended June 30, 2025 and 2024[72](index=72&type=chunk) [Note 7. Accrued Expenses and Other Current Liabilities](index=20&type=section&id=Note%207.%20Accrued%20Expenses%20and%20Other%20Current%20Liabilities) Accrued Expenses and Other Current Liabilities (in thousands) | Item | June 30, 2025 | December 31, 2024 | | :--- | :--- | :--- | | Accrued contract research and development costs | $9,133 | $9,070 | | Employee compensation costs | $3,351 | $4,311 | | Professional fees | $692 | $227 | | Other liabilities | $416 | $500 | | Total | $13,592 | $14,108 | - Total accrued expenses and other current liabilities decreased from **$14.1 million** at December 31, 2024, to **$13.6 million** at June 30, 2025, mainly due to a decrease in employee compensation costs, partially offset by an increase in professional fees[73](index=73&type=chunk) [Note 8. Term Loan Facility](index=20&type=section&id=Note%208.%20Term%20Loan%20Facility) - IO Biotech ApS entered into a Finance Contract with the **European Investment Bank (EIB)** for a loan facility of up to **€57.5 million**, including three committed tranches (up to **€37.5 million**) and one uncommitted accordion tranche (**€20.0 million**)[74](index=74&type=chunk) - **Tranche A (€10.0 million)** was drawn on May 6, 2025, and **Tranche B (€12.5 million)** was drawn on July 4, 2025. **Tranche C (€15.0 million)** is subject to conditions, including raising an additional **$50.0 million** and submitting a marketing authorization application for **Cylembio®**[75](index=75&type=chunk)[76](index=76&type=chunk) - The loans bear a fixed interest rate of **8% annually**, payable at their respective maturity dates (six years after disbursement). The company also issued Tranche A and Tranche B warrants to EIB, valued at **$5.0 million** and **$5.7 million**, respectively, classified as liability[77](index=77&type=chunk)[87](index=87&type=chunk)[88](index=88&type=chunk) Term Loan Debt, Net (in thousands) | Item | June 30, 2025 | | :--- | :--- | | Term loan debt principal | $11,720 | | Amortized paid-in-kind interest | $142 | | Less: Unamortized debt issuance costs | $(5,290) | | Currency adjustments | $148 | | Total term loan debt, net | $6,720 | EIB Warrants Issued and Outstanding (June 30, 2025) | Warrant Type | Outstanding Shares | Exercise Price | | :--- | :--- | :--- | | Tranche A | 5,623,664 | $0.89 | | Tranche B | 4,221,868 | $1.32 | [Note 9. Leases](index=24&type=section&id=Note%209.%20Leases) - As of June 30, 2025, the company has a right-of-use lease asset of **$1.5 million** and corresponding current and non-current lease liabilities of **$0.8 million** and **$0.9 million**, respectively, primarily for office and laboratory spaces in Copenhagen, New York, and Rockville[93](index=93&type=chunk) Lease Cost and Cash Flows (in thousands) | Metric | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | | Operating lease cost | $359 | $369 | | Operating cash flows paid for lease liabilities | $413 | $385 | | Remaining average lease term (years) | 2.1 | 3.0 | | Weighted average discount rate | 6.4% | 6.3% | Future Lease Payments (Undiscounted, in thousands) | Year | Amount | | :--- | :--- | | Remainder of 2025 | $419 | | 2026 | $863 | | 2027 | $470 | | Total | $1,752 | [Note 10. Commitments and Contingencies](index=25&type=section&id=Note%2010.%20Commitments%20and%20Contingencies) - The company was not subject to any **material legal proceedings** during the six months ended June 30, 2025, and no material legal proceedings are currently pending or threatened[96](index=96&type=chunk)[223](index=223&type=chunk) - Contractual obligations for clinical trials, preclinical research, and manufacturing generally allow for termination with **30 to 90 days' notice**, and noncancelable obligations are not considered material[97](index=97&type=chunk)[192](index=192&type=chunk) - The company enters into indemnification agreements with various parties, including officers and directors, for certain claims, but it is not possible to estimate the maximum potential liability[98](index=98&type=chunk)[99](index=99&type=chunk) [Note 11. Stockholders' Equity](index=27&type=section&id=Note%2011.%20Stockholders%27%20Equity) - As of June 30, 2025, and December 31, 2024, the company had **65,880,914 common shares outstanding**, with **300,000,000 shares authorized**[100](index=100&type=chunk)[106](index=106&type=chunk) - In August 2023, the company completed a private placement, selling **37,065,647 common shares** and an equal number of warrants for **$2.025 per unit**, generating **$71.9 million** in net proceeds[101](index=101&type=chunk)[103](index=103&type=chunk) - The warrants from the private placement are exercisable at **$2.47 per share** until February 9, 2027, and are classified as a component of permanent stockholders' equity[102](index=102&type=chunk)[104](index=104&type=chunk) [Note 12. Equity-Based Compensation](index=27&type=section&id=Note%2012.%20Equity-Based%20Compensation) - The **2021 Equity and Incentive Plan** had **486,563 shares** available for future grant as of June 30, 2025, and the **2023 Inducement Award Plan** had **1,666,427 shares** available[107](index=107&type=chunk)[109](index=109&type=chunk) Stock Options Activity (Six Months Ended June 30, 2025) | Metric | Number of stock options | Weighted average exercise price per share | | :--- | :--- | :--- | | Outstanding, January 1, 2025 | 8,967,605 | $5.18 | | Granted | 2,709,284 | $1.13 | | Cancelled or forfeited | (137,589) | $4.28 | | Outstanding, June 30, 2025 | 11,539,300 | $4.24 | | Exercisable, June 30, 2025 | 5,537,588 | $6.87 | Equity-Based Compensation Expense (in thousands) | Expense Type | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Research and development | $644 | $677 | $1,262 | $1,290 | | General and administrative | $963 | $965 | $1,914 | $1,920 | | Total | $1,607 | $1,642 | $3,176 | $3,210 | - Unrecognized compensation cost related to unvested stock-based awards was **$7.2 million** as of June 30, 2025, expected to be recognized over a weighted average period of **2.8 years**[112](index=112&type=chunk) [Note 13. Income Taxes](index=31&type=section&id=Note%2013.%20Income%20Taxes) - Income tax expense was **$0.1 million** for the three months and **$0.3 million** for the six months ended June 30, 2025, a decrease from the prior year periods[114](index=114&type=chunk) - The company maintains a **full valuation allowance** against all deferred tax assets due to a history of cumulative net losses and lack of commercial products, indicating uncertainty in realizing these benefits[114](index=114&type=chunk)[115](index=115&type=chunk) [Note 14. Net Loss Per Share](index=31&type=section&id=Note%2014.%20Net%20Loss%20Per%20Share) Net Loss Per Common Share (Basic and Diluted) | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Net loss | $(26,217) | $(20,686) | $(48,638) | $(40,143) | | Net loss per common share | $(0.40) | $(0.31) | $(0.74) | $(0.61) | | Weighted-average shares | 65,880,914 | 65,880,914 | 65,880,914 | 65,880,914 | - Basic and diluted net loss per common share increased to **$(0.40)** for Q2 2025 and **$(0.74)** for the six months ended June 30, 2025, compared to **$(0.31)** and **$(0.61)** in the respective prior year periods[116](index=116&type=chunk) - Potentially dilutive securities, including stock options and warrants, were excluded from diluted EPS calculation as their effect was anti-dilutive due to the net loss[116](index=116&type=chunk) [Note 15. Segments](index=31&type=section&id=Note%2015.%20Segments) - The company operates as a **single operating segment**, focusing on developing therapeutic cancer vaccines based on its **T-win® platform**, with the CEO managing the company and allocating resources on an aggregate basis[117](index=117&type=chunk) Research and Development Expenses by Category (in thousands) | Category | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Clinical trial-related activities | $6,390 | $6,637 | $14,081 | $13,785 | | Personnel | $6,531 | $5,123 | $12,714 | $9,917 | | Chemistry, manufacturing and control | $2,484 | $2,994 | $4,776 | $5,161 | | Preclinical studies and activities | $616 | $295 | $1,028 | $632 | | Other costs | $631 | $799 | $428 | $664 | | Total | $16,652 | $15,848 | $33,027 | $30,159 | General and Administrative Expenses by Category (in thousands) | Category | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :--- | :--- | :--- | :--- | :--- | | Personnel | $2,840 | $2,899 | $5,852 | $5,693 | | Professional services | $1,743 | $975 | $3,124 | $2,048 | | Other costs | $1,935 | $1,811 | $3,751 | $3,830 | | Total | $6,518 | $5,685 | $12,727 | $11,571 | [Note 16. Subsequent Events](index=32&type=section&id=Note%2016.%20Subsequent%20Events) - On July 4, 2025, President Trump signed the **One Big Beautiful Bill Act**, which includes measures potentially affecting the company's income tax provision, such as permanent and immediate deduction for domestic R&D expenditures[120](index=120&type=chunk) - On July 4, 2025, the company drew **€12.5 million** from the **EIB Tranche B loan facility**, following the issuance of Tranche B Warrants on June 24, 2025, to purchase **4,221,867.59 common shares** at a strike price of **$1.32**[121](index=121&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=33&type=section&id=Item%202.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides an overview of the company's business, product pipeline, clinical trial progress, and a detailed analysis of its financial condition and results of operations for the three and six months ended June 30, 2025, compared to the prior year. It also discusses liquidity, capital resources, and critical accounting policies [Overview](index=33&type=section&id=Overview) - IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines using its **T-win® platform**[124](index=124&type=chunk) - The lead candidate, **Cylembio® (IO102-IO103)**, targets IDO and PD-L1. A Phase 1/2 trial in metastatic melanoma showed a confirmed **ORR of 73%** and median **PFS of 25.5 months** in combination with nivolumab, leading to **FDA Breakthrough Therapy Designation**[124](index=124&type=chunk) - Topline results from the Phase 3 trial (IOB-013/KN-D18) of **Cylembio** plus **KEYTRUDA®** for first-line advanced melanoma showed clinical improvement in PFS (median **19.4 months** vs. **11.0 months** for pembrolizumab alone), but narrowly missed statistical significance (**p=0.056**)[124](index=124&type=chunk) - A trend toward improved overall survival was observed, with results projected for **2026**. The company plans to discuss the data with the **FDA** in **Fall 2025** for a potential **Biologics License Application (BLA)** submission[124](index=124&type=chunk)[134](index=134&type=chunk) [T-win Platform](index=34&type=section&id=T-win%20Platform) - The **T-win platform** is a novel approach to therapeutic cancer vaccines designed to activate pre-existing T cells to target immunosuppressive mechanisms, employing a dual mechanism of action: direct killing of immune-suppressive cells and modulation of the tumor microenvironment[125](index=125&type=chunk) - Product candidates like **IO102-IO103** target IDO and PD-L1, while **IO112** targets Arginase 1, and **IO170** targets TGFβ, aiming to amplify immune-oncology treatment effects across various tumor types[125](index=125&type=chunk) [Product Pipeline and Milestones](index=34&type=section&id=Product%20Pipeline%20and%20Milestones) Product Pipeline and Expected Upcoming Milestones | Product Candidates | Line of therapy/indication | Pre-clinical | Phase 1 | Phase 2 | Phase 3 | Takeaways & next steps | | :--- | :--- | :--- | :--- | :--- | :--- | :--- | | Cylembio® IO102-IO103 (Targets: IDO1, PD-L1) | IOB-013: First Line Advanced Melanoma* | | | | X | Cylembio demonstrated clinical improvement in PFS, narrow miss on statistical significance. Plans to discuss data with FDA in Fall 2025; potential US BLA submission. | | | IOB-022: First Line Solid Tumors* (Lung (NSCLC), Head & Neck (SCCHN)) | | | X | | SCCHN: Primary endpoint met. NSCLC: Encouraging data. | | | IOB-032: Neoadjuvant / Adjuvant Solid Tumors* (Melanoma, Head & Neck (SCCHN)) | | | X | | Enrollment completed in January 2025. Data available 2H25; presented in 2026. | | IO112 (Target: Arginase 1) | Solid Tumors (Indications TBD) | X | | | | Next pipeline candidate expected to enter clinical development. | | IO170 (Target: TGFB) | Solid Tumors (Indications TBD) | X | | | | Early-stage pipeline candidate. | * In combination with pembrolizumab [Potentially Registrational Phase 3 IOB-013/KN-D18 Trial](index=34&type=section&id=Potentially%20Registrational%20Phase%203%20IOB-013%2FKN-D18%20Trial) - The Phase 3 IOB-013/KN-D18 trial for **Cylembio®** in combination with **pembrolizumab** for first-line advanced melanoma enrolled **407 patients** and demonstrated a median **PFS of 19.4 months** versus **11.0 months** for pembrolizumab alone, narrowly missing statistical significance (**p=0.056**)[129](index=129&type=chunk)[130](index=130&type=chunk) - PFS improvement was observed across most subgroups, with a profound effect in **PD-L1 negative patients** (**HR: 0.54**, mPFS **16.6 months** vs. **3.0 months**). The combination was well tolerated with no new safety signals[131](index=131&type=chunk)[133](index=133&type=chunk) - The company plans to meet with the **FDA** in **Fall 2025** to discuss the data and determine next steps for a potential **Biologics License Application (BLA)** submission[134](index=134&type=chunk) [Phase 2 IOB-022/KN-D38 Basket Trial](index=36&type=section&id=Phase%202%20IOB-022%2FKN-D38%20Basket%20Trial) - The Phase 2 IOB-022/KN-D38 basket trial investigated **IO102-IO103** with **pembrolizumab** in first-line metastatic NSCLC and SCCHN. The SCCHN cohort (B) met its primary endpoint with a confirmed **ORR of 44.4%** and a **6.6-month median PFS**[135](index=135&type=chunk)[136](index=136&type=chunk) - Preliminary results for the NSCLC cohort (A) showed promising activity with a **48% confirmed ORR** and an **8.1-month median PFS**. The safety profile was consistent with anti-PD-1 monotherapy, with no significant added systemic toxicity[137](index=137&type=chunk)[138](index=138&type=chunk) - The efficacy results from the SCCHN cohort satisfied conditions for accessing the **EIB Tranche B loan of €12.5 million**, which was drawn on July 4, 2025[136](index=136&type=chunk) [Phase 2 IOB-032/PN-E40 Basket Trial](index=36&type=section&id=Phase%202%20IOB-032%2FPN-E40%20Basket%20Trial) - The Phase 2 IOB-032/PN-E40 trial evaluates **IO102-IO103** in combination with **pembrolizumab** as neoadjuvant/adjuvant therapy for resectable melanoma and SCCHN. Enrollment for all cohorts was completed in **January 2025**[139](index=139&type=chunk)[140](index=140&type=chunk) - The primary endpoint is **major pathological response** at surgery. Data is expected in the **second half of 2025** and will be presented at a medical meeting in **2026**[140](index=140&type=chunk) [Preclinical Development](index=38&type=section&id=Preclinical%20Development) - **IO112**, targeting Arginase 1, is an **IND-ready T-win® vaccine candidate** that demonstrated anti-tumor activity and dynamic changes in the TME in preclinical studies. An **IND filing** is anticipated in **2026**[141](index=141&type=chunk)[143](index=143&type=chunk) - **IO170**, targeting TGFβ, is an early-stage pipeline candidate. Preclinical data showed significant tumor growth inhibition in breast and prostate cancer models, with **IND-enabling studies** planned for **2025** and **2026**[145](index=145&type=chunk)[146](index=146&type=chunk) [Development of IO102 and IO103](index=38&type=section&id=Development%20of%20IO102%20and%20IO103) - The development of **IO102-IO103** is based on prior separate development of **IO102 (IDO1-derived peptide)** and **IO103**. **IO102** showed proof-of-concept in a Phase 1 NSCLC trial with **47% clinical benefit** and **26 months OS**[147](index=147&type=chunk) - New non-clinical data presented in **April 2025** further supports the **dual mechanism of action** of **IO102-IO103**, demonstrating strong T-cell responses, tumor growth control, and unique molecular changes not seen with PD-1/PD-L1 inhibitors[148](index=148&type=chunk)[149](index=149&type=chunk) [Components of Operating Results](index=40&type=section&id=Components%20of%20Operating%20Results) [Research and Development](index=40&type=section&id=Research%20and%20Development) - Research and development expenses primarily include personnel costs, external consultant and CRO/CMO expenses, laboratory costs, and intellectual property-related fees. All R&D costs are expensed as incurred[155](index=155&type=chunk)[156](index=156&type=chunk)[162](index=162&type=chunk) - The company expects significant R&D expenses to continue as it advances product candidates through clinical development, manufacturing, and regulatory approvals[160](index=160&type=chunk) - Substantially all direct R&D expenses are focused on **Cylembio®**, used across its three ongoing clinical trials[159](index=159&type=chunk) [General and Administrative Expenses](index=44&type=section&id=General%20and%20Administrative%20Expenses) - General and administrative expenses consist mainly of personnel costs (salaries, benefits, equity-based compensation), professional services (legal, HR, audit, accounting), and facility-related fees[166](index=166&type=chunk) - These expenses are expected to remain significant as the company supports R&D, manufacturing, and operates as a public company, including costs for compliance and retaining key personnel[166](index=166&type=chunk) [Other Income (Expense), Net](index=44&type=section&id=Other%20Income%20(Expense)%2C%20Net) - Other income (expense), net includes foreign currency exchange gains/losses, interest income from money market funds, interest expense on the EIB debt, and changes in the fair value of warrants[168](index=168&type=chunk) [Results of Operations](index=45&type=section&id=Results%20of%20Operations) [Comparison of the three months ended June 30, 2025 and 2024](index=45&type=section&id=Comparison%20of%20the%20three%20months%20ended%20June%2030%2C%202025%20and%202024) Operating Results (Three Months Ended June 30, in thousands) | Metric | 2025 | 2024 | Change Amount | Change Percent | | :--- | :--- | :--- | :--- | :--- | | Research and development | $16,652 | $15,848 | $804 | 5.1% | | General and administrative | $6,518 | $5,685 | $833 | 14.7% | | Total operating expenses | $23,170 | $21,533 | $1,637 | 7.6% | | Loss from operations | $(23,170) | $(21,533) | $(1,637) | 7.6% | | Other (expense) income, net | $(2,929) | $1,221 | $(4,150) | (339.9)% | | Net loss | $(26,217) | $(20,686) | $(5,531) | 26.7% | - Research and development expenses increased by **$0.8 million (5.1%)** to **$16.7 million**, primarily due to a **$1.4 million** increase in personnel expenses, partially offset by a **$0.5 million** decrease in manufacturing activities[170](index=170&type=chunk) - General and administrative expenses increased by **$0.8 million (14.7%)** to **$6.5 million**, mainly driven by a rise in professional services, particularly legal expenses[171](index=171&type=chunk) - Other income (expense), net decreased by **$4.2 million** to **$(2.9) million**, primarily due to a **$2.6 million** change in fair value of EIB warrants and a **$1.0 million** decrease in interest income[172](index=172&type=chunk) [Comparison of the six months ended June 30, 2025 and 2024](index=46&type=section&id=Comparison%20of%20the%20six%20months%20ended%20June%2030%2C%202025%20and%202024) Operating Results (Six Months Ended June 30, in thousands) | Metric | 2025 | 2024 | Change Amount | Change Percent | | :--- | :--- | :--- | :--- | :--- | | Research and development | $33,027 | $30,159 | $2,868 | 9.5% | | General and administrative | $12,727 | $11,571 | $1,156 | 10.0% | | Total operating expenses | $45,754 | $41,730 | $4,024 | 9.6% | | Loss from operations | $(45,754) | $(41,730) | $(4,024) | 9.6% | | Other (expense) income, net | $(2,620) | $2,376 | $(4,996) | (210.3)% | | Net loss | $(48,638) | $(40,143) | $(8,495) | 21.2% | - Research and development expenses increased by **$2.9 million (9.5%)** to **$33.0 million**, primarily due to a **$2.8 million** increase in personnel and contractor-related costs[174](index=174&type=chunk) - General and administrative expenses increased by **$1.2 million (10.0%)** to **$12.7 million**, mainly due to a **$1.1 million** increase in legal expenses within professional services[175](index=175&type=chunk) - Other (expense) income, net decreased by **$5.0 million** to **$(2.6) million**, primarily driven by a **$2.6 million** change in fair value of EIB warrants and a **$2.2 million** decrease in interest income[176](index=176&type=chunk) [Liquidity and Capital Resources](index=47&type=section&id=Liquidity%20and%20Capital%20Resources) [Sources of Liquidity](index=47&type=section&id=Sources%20of%20Liquidity) - The company's operations have been financed by **$386.4 million** in net proceeds from convertible preference shares, notes, IPO, Private Placement, and the EIB Loan Facility[177](index=177&type=chunk) - As of June 30, 2025, cash and cash equivalents were **$28.1 million**. With the **€12.5 million EIB Tranche B funds** drawn on July 4, 2025, existing capital is expected to fund development activities into **Q1 2026**[152](index=152&type=chunk)[181](index=181&type=chunk) - The EIB Loan Facility provides up to **€57.5 million**, with **€15.0 million** in committed funds contingent on conditions and **€20.0 million** in uncommitted funds[178](index=178&type=chunk) - The company has an **at-the-market equity program** for up to **$75.0 million**, but no shares have been issued under it as of June 30, 2025[180](index=180&type=chunk) [Cash Flows](index=48&type=section&id=Cash%20Flows) Summary of Cash Flows (Six Months Ended June 30, in thousands) | Cash Flow Type | 2025 | 2024 | | :--- | :--- | :--- | | Net cash used in operating activities | $(42,893) | $(41,914) | | Net cash used in investing activities | $(54) | $(23) | | Net cash provided by financing activities | $11,487 | — | | Net decrease in cash and cash equivalents | $(31,460) | $(41,937) | [Net Cash Used in Operating Activities](index=48&type=section&id=Net%20Cash%20Used%20in%20Operating%20Activities) - Net cash used in operating activities was **$42.9 million** for the six months ended June 30, 2025, primarily due to a net loss of **$48.6 million**, partially offset by **$7.0 million** in non-cash items (equity-based compensation, change in fair value of warrants)[183](index=183&type=chunk) [Net Cash Used in Investing Activities](index=48&type=section&id=Net%20Cash%20Used%20in%20Investing%20Activities) - Cash used in investing activities was minimal, at **$0.1 million** for the six months ended June 30, 2025, and **$0.02 million** for the same period in 2024, related to property and equipment purchases[185](index=185&type=chunk) [Net Cash Provided by Financing Activities](index=48&type=section&id=Net%20Cash%20Provided%20by%20Financing%20Activities) - Net cash provided by financing activities was **$11.5 million** for the six months ended June 30, 2025, entirely from the net proceeds of the **EIB Tranche A loan facility** funding[186](index=186&type=chunk) [Funding Requirements](index=50&type=section&id=Funding%20Requirements) - The company anticipates continued losses and increasing R&D, G&A, and capital expenditures. Existing cash and cash equivalents, plus the **EIB Tranche B funds**, are expected to fund operations into **Q1 2026**[187](index=187&type=chunk)[188](index=188&type=chunk) - Additional financing will be required to advance product candidates and fund operations, which may involve equity offerings, debt financings, or collaborations, potentially leading to dilution or restrictive covenants[188](index=188&type=chunk) - Future funding needs depend on factors such as clinical trial progress, regulatory outcomes, commercialization costs, intellectual property maintenance, and the ability to secure non-dilutive funding[189](index=189&type=chunk)[196](index=196&type=chunk) [Contractual Obligations and Commitments](index=52&type=section&id=Contractual%20Obligations%20and%20Commitments) - The company has operating leases for office and laboratory spaces in Copenhagen, Rockville, and New York, with terms expiring between **May 2025** and **December 2027**[191](index=191&type=chunk) - Contracts with third-party service providers for clinical trials, research, and manufacturing generally allow for termination with **30 to 90 days' notice**, and non-cancelable obligations are not considered material[192](index=192&type=chunk) [Critical Accounting Policies and Significant Judgments and Estimates](index=52&type=section&id=Critical%20Accounting%20Policies%20and%20Significant%20Judgments%20and%20Estimates) [Going Concern](index=52&type=section&id=Going%20Concern) - Management has concluded that there is **substantial doubt** about the company's ability to continue as a **going concern** for one year after the financial statements are issued, as current cash and **EIB Tranche B funds** are insufficient to cover operating expenses and capital requirements beyond **Q1 2026**[195](index=195&type=chunk) [Research and Development Costs](index=54&type=section&id=Research%20and%20Development%20Costs) - The company estimates R&D costs for activities performed by CMOs, CROs, and other vendors, recognizing expenses based on estimated progress and contracted amounts. Significant judgments are made in determining accrued liabilities and prepaid expenses[197](index=197&type=chunk)[198](index=198&type=chunk)[199](index=199&type=chunk) [Equity-based Compensation](index=54&type=section&id=Equity-based%20Compensation) - Equity-based compensation awards are measured at fair value on the grant date and expensed over the vesting period. The **Black-Scholes option pricing model** is used, requiring assumptions for fair value, expected life, volatility, and risk-free interest rate[201](index=201&type=chunk)[202](index=202&type=chunk) [Income Taxes](index=54&type=section&id=Income%20Taxes) - Deferred tax assets and liabilities are recognized for temporary differences and carryforwards, measured using enacted statutory tax rates. A **full valuation allowance** is maintained against net deferred tax assets due to historical operating losses and uncertainty of future taxable income[204](index=204&type=chunk)[205](index=205&type=chunk) - Tax benefits from uncertain tax positions are recognized only if it's more likely than not they will be sustained, measured at the largest likely realized amount[206](index=206&type=chunk) [Warrants Issued in Connection with a Sale of Common Stock or Issuance of Debt](index=56&type=section&id=Warrants%20Issued%20in%20Connection%20with%20a%20Sale%20of%20Common%20Stock%20or%20Issuance%20of%20Debt) - Warrants are classified as liabilities or equity based on **ASC 480-10** or **ASC 815-40**. Liability-classified warrants are measured at fair value through profit or loss, while equity-classified warrants are allocated proceeds based on relative fair values at issuance[209](index=209&type=chunk)[210](index=210&type=chunk) [Recently Adopted Significant Accounting Policies](index=56&type=section&id=Recently%20Adopted%20Significant%20Accounting%20Policies) - Refer to **Note 2** for details on recently issued accounting standards and their potential impact[211](index=211&type=chunk) [Off-Balance Sheet Arrangements](index=56&type=section&id=Off-Balance%20Sheet%20Arrangements) - The company did not have any **off-balance sheet arrangements** as defined under SEC rules during the periods presented[212](index=212&type=chunk) [Emerging Growth Company ("EGC") Status](index=56&type=section&id=Emerging%20Growth%20Company%20(%22EGC%22)%20Status) - As an **Emerging Growth Company (EGC)** under the **JOBS Act**, the company utilizes reduced disclosure requirements and has elected to delay the adoption of certain new or revised accounting standards[213](index=213&type=chunk)[214](index=214&type=chunk) - The company may remain an EGC until **December 31, 2026**, unless its non-affiliate common stock market value exceeds **$700 million**, annual gross revenues reach **$1.235 billion**, or it issues over **$1.0 billion** in non-convertible debt[215](index=215&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=58&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, IO Biotech, Inc. is not required to provide quantitative and qualitative disclosures about market risk - The company is a **smaller reporting company** and is not required to provide quantitative and qualitative disclosures about market risk[216](index=216&type=chunk) [Item 4. Controls and Procedures](index=58&type=section&id=Item%204.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and procedures were not effective as of June 30, 2025, due to a previously identified material weakness in internal control over financial reporting related to CRO-related accruals and prepayments. Remediation efforts are ongoing - Management, with CEO and CFO participation, concluded that disclosure controls and procedures were **not effective** as of **June 30, 2025**[217](index=217&type=chunk)[219](index=219&type=chunk) - A **material weakness** was identified in internal control over financial reporting related to the accounting for CRO-related accruals and prepayments, specifically concerning the accounting framework and processes for ongoing clinical trials[219](index=219&type=chunk) - Remediation efforts are underway and expected to be fully implemented during the fiscal year ending **December 31, 2025**, but the material weakness will not be considered fully remediated until new controls are operational and tested effectively[220](index=220&type=chunk) - There has been **no change** in internal control over financial reporting during the most recently completed fiscal quarter that materially affected, or is reasonably likely to materially affect, internal control over financial reporting[221](index=221&type=chunk) [PART II. OTHER INFORMATION](index=59&type=section&id=PART%20II.%20OTHER%20INFORMATION) [Item 1. Legal Proceedings](index=59&type=section&id=Item%201.%20Legal%20Proceedings) The company is not currently a party to any material legal proceedings and believes that the outcome of ordinary course litigation will not have a material adverse effect on its business - The company is not currently a party to any **material legal proceedings** and believes that the final outcome of ordinary course matters will not have a material adverse effect on its business[223](index=223&type=chunk) [Item 1A. Risk Factors](index=60&type=section&id=Item%201A.%20Risk%20Factors) This section outlines numerous material risks associated with the company's business, including its limited operating history, substantial doubt about its ability to continue as a going concern, dependence on product candidate success, regulatory approval challenges, manufacturing complexities, intense competition, intellectual property protection issues, and general operational and market risks [Summary of the Material and Other Risks Associated with Our Business](index=60&type=section&id=Summary%20of%20the%20Material%20and%20Other%20Risks%20Associated%20with%20Our%20Business) - Key risks include a limited operating history with recurring losses, **substantial doubt about going concern**, the need for additional funding, and the absence of marketing approval for any product candidates, including **Cylembio®**[227](index=227&type=chunk) - Other significant risks involve potential clinical trial failures, reliance on third-party manufacturers, intense competition, challenges in intellectual property protection, and the impact of public health emergencies or geopolitical events[227](index=227&type=chunk) - The company also faces risks related to regulatory changes, data privacy and security, and a **material weakness** in internal control over financial reporting[230](index=230&type=chunk) [Risks Related to Limited Operating History, Financial Position and Capital Requirements](index=62&type=section&id=Risks%20Related%20to%20Limited%20Operating%20History%2C%20Financial%20Position%20and%20Capital%20Requirements) - The company has a limited operating history, has incurred net losses since inception (**$48.6 million** for H1 2025), and expects to continue incurring significant losses, raising **substantial doubt** about its ability to continue as a **going concern**[228](index=228&type=chunk)[231](index=231&type=chunk) - Existing cash and cash equivalents, even with the **EIB Tranche B funds**, are only sufficient to fund development activities into **Q1 2026**, necessitating substantial additional funding[233](index=233&type=chunk) - Failure to raise additional capital when needed could force delays, reductions, or elimination of product development programs, or even cessation of operations, and may lead to dilution for existing stockholders or restrictive debt covenants[236](index=236&type=chunk)[237](index=237&type=chunk)[238](index=238&type=chunk) [Risks Related to the Discovery, Development and Regulatory Approval of Our Product Candidates](index=67&type=section&id=Risks%20Related%20to%20the%20Discovery%2C%20Development%20and%20Regulatory%20Approval%20of%20Our%20Product%20Candidates) - None of the company's product candidates, including **Cylembio®**, have received marketing approval, and successful advancement through clinical development and regulatory approval is uncertain and critical for business success[240](index=240&type=chunk)[241](index=241&type=chunk)[243](index=243&type=chunk) - The Phase 3 trial for **Cylembio®** narrowly missed statistical significance on its primary endpoint (**PFS**), potentially requiring additional data or trials for regulatory approval and extending commercialization timelines[245](index=245&type=chunk) - Preclinical and early clinical trial results are not always predictive of later-stage outcomes, and product candidates based on novel **T-win® platform** technologies face unpredictable development, timing, and costs[246](index=246&type=chunk)[247](index=247&type=chunk) - Delays or difficulties in clinical trial site activation, patient enrollment, or retention could hinder regulatory approvals. The **FDA's Breakthrough Therapy Designation** for **IO102-IO103** does not guarantee faster development or approval[252](index=252&type=chunk)[255](index=255&type=chunk)[273](index=273&type=chunk)[274](index=274&type=chunk) - Regulatory approval processes are lengthy and unpredictable, and product candidates could fail to receive approval due to various factors, including disagreement with trial design, insufficient safety/efficacy data, or manufacturing issues[257](index=257&type=chunk)[258](index=258&type=chunk)[259](index=259&type=chunk) [Risks Related to Ongoing Regulatory Obligations and Review](index=76&type=section&id=Risks%20Related%20to%20Ongoing%20Regulatory%20Obligations%20and%20Review) - Even if approved, product candidates will be subject to extensive and ongoing regulatory requirements, including post-marketing studies, labeling restrictions, and compliance with **cGMP** and **GCP**[275](index=275&type=chunk)[276](index=276&type=chunk) - Later discovery of unknown problems or non-compliance could lead to severe consequences such as product withdrawal, labeling revisions, fines, or refusal of pending applications[277](index=277&type=chunk)[280](index=280&type=chunk) - The company's product candidates are expected to be used in combination with third-party drugs (e.g., **pembrolizumab**), over which the company has limited control regarding supply, regulatory status, or approval, posing risks to development and commercialization[279](index=279&type=chunk)[281](index=281&type=chunk)[283](index=283&type=chunk) [Resource Allocation Risks](index=78&type=section&id=Resource%20Allocation%20Risks) - With limited resources, the company must prioritize R&D, potentially forgoing more profitable opportunities or relinquishing valuable rights to product candidates through collaborations[284](index=284&type=chunk) [Product Candidate Success and Commercialization Risks](index=78&type=section&id=Product%20Candidate%20Success%20and%20Commercialization%20Risks) - The company's success heavily relies on the development and regulatory approval of its limited product candidates (**Cylembio®**, **IO112**, **IO170**). Failure of any could significantly impact revenue and profitability[285](index=285&type=chunk)[286](index=286&type=chunk) - Difficulty in enrolling or retaining patients in clinical trials, due to factors like competition or eligibility criteria, could delay or prevent regulatory approvals and increase development costs[287](index=287&type=chunk)[288](index=288&type=chunk)[289](index=289&type=chunk)[290](index=290&type=chunk)[291](index=291&type=chunk) [International Market Penetration Risks](index=80&type=section&id=International%20Market%20Penetration%20Risks) - Future growth depends on penetrating multiple international markets, which exposes the company to risks such as foreign currency fluctuations, adverse tax consequences, complex regulatory requirements, differing medical practices, and price controls[292](index=292&type=chunk)[294](index=294&type=chunk) - Adverse global economic conditions or political instability could affect purchasing decisions, reimbursement obligations, and milestone payments, materially harming the business[295](index=295&type=chunk) [Risks Related to Manufacturing and Commercialization](index=82&type=section&id=Risks%20Related%20to%20Manufacturing%20and%20Commercialization) - Manufacturing product candidates is complex, and difficulties in production, quality control, or regulatory compliance by CMOs could delay clinical trials or product supply, increasing costs[296](index=296&type=chunk)[297](index=297&type=chunk)[298](index=298&type=chunk) - Changes in manufacturing or formulation may require additional testing or regulatory approval, leading to delays and increased costs[300](index=300&type=chunk) - Market acceptance of approved products is uncertain and depends on factors like efficacy, safety, cost, reimbursement, and physician/patient adoption. Failure to achieve broad market acceptance would harm the business[301](index=301&type=chunk)[302](index=302&type=chunk)[303](index=303&type=chunk) - Unfavorable pricing regulations or inadequate third-party coverage and reimbursement policies could make commercialization unprofitable, as patients rely on payors to cover costs[304](index=304&type=chunk)[306](index=306&type=chunk)[307](index=307&type=chunk) - Governmental cost containment initiatives, such as the **'most-favored-nation' pricing policy** or the **Inflation Reduction Act**, could further reduce product prices and reimbursement rates, impacting profitability[309](index=309&type=chunk)[311](index=311&type=chunk)[312](index=312&type=chunk)[313](index=313&type=chunk)[314](index=314&type=chunk)[315](index=315&type=chunk) [Sales and Marketing Capabilities Risks](index=86&type=section&id=Sales%20and%20Marketing%20Capabilities%20Risks) - If approved, the company must establish its own sales and marketing capabilities or outsource these functions. Both options involve significant risks, including high costs, recruitment challenges, and reliance on third-party efforts[317](index=317&type=chunk)[318](index=318&type=chunk)[319](index=319&type=chunk) - Failure to successfully establish sales and marketing capabilities, either internally or through third parties, would prevent successful commercialization of product candidates[319](index=319&type=chunk) [Off-Label Promotion and Regulatory Compliance Risks](index=88&type=section&id=Off-Label%20Promotion%20and%20Regulatory%20Compliance%20Risks) - Regulatory approval is limited to specific indications. Promoting products for unapproved (**'off-label'**) uses or inconsistently with approved labeling could lead to substantial fines, criminal penalties, injunctions, and reputational damage[320](index=320&type=chunk)[321](index=321&type=chunk)[322](index=322&type=chunk) - Engaging in impermissible promotion could also trigger false claims litigation under federal and state statutes, resulting in civil and criminal penalties, exclusion from healthcare programs, and burdensome compliance obligations[324](index=324&type=chunk) - Off-label use could harm the company's reputation and increase the risk of product liability suits[326](index=326&type=chunk) [International Regulatory Approval Risks](index=89&type=section&id=International%20Regulatory%20Approval%20Risks) - Approval in one jurisdiction (e.g., US or EU) does not guarantee approval in others. Varying regulatory requirements, additional testing, and administrative reviews in foreign countries could delay or prevent international commercialization[327](index=327&type=chunk)[328](index=328&type=chunk)[329](index=329&type=chunk) - Failure to comply with international regulatory requirements or delays in approvals would reduce the target market and limit the full market potential of any approved products[329](index=329&type=chunk) [Risks Related to Reliance on Third Parties](index=89&type=section&id=Risks%20Related%20to%20Reliance%20on%20Third%20Parties) - The company relies on third parties (CROs, clinical investigators) to conduct clinical trials and research. Lack of control over these parties' conduct, adherence to protocols, or meeting deadlines could delay development programs or increase costs[330](index=330&type=chunk)[331](index=331&type=chunk)[332](index=332&type=chunk)[333](index=333&type=chunk)[334](index=334&type=chunk) - Reliance on third-party CMOs for manufacturing product candidates exposes the company to risks of production difficulties, quality deviations, supply interruptions, and failure to comply with **cGMP** regulations, which could halt or delay clinical trials and commercialization[335](index=335&type=chunk)[336](index=336&type=chunk)[337](index=337&type=chunk)[338](index=338&type=chunk)[339](index=339&type=chunk)[340](index=340&type=chunk)[341](index=341&type=chunk) - Dependence on limited or sole-source third-party suppliers for specialty materials and equipment creates risks of supply reduction or interruption, potentially delaying clinical studies and commercialization[342](index=342&type=chunk)[343](index=343&type=chunk)[344](index=344&type=chunk) - Sharing trade secrets with third parties increases the risk of misappropriation or disclosure, potentially eroding the company's competitive position[345](index=345&type=chunk)[346](index=346&type=chunk) - Future partnerships, collaborations, or licensing arrangements may not yield expected benefits, could incur significant costs, dilute existing stockholders, or divert management attention[347](index=347&type=chunk)[348](index=348&type=chunk)[349](index=349&type=chunk) [Risks Related to Our Industry and Business Operations](index=96&type=section&id=Risks%20Related%20to%20Our%20Industry%20and%20Business%20Operations) - Disruptions at regulatory agencies (**FDA**, **EMA**, **SEC**) due to policy changes, funding shortages, or personnel issues could delay product development, regulatory reviews, or approvals, negatively impacting the business[351](index=351&type=chunk)[352](index=352&type=chunk)[353](index=353&type=chunk)[354](index=354&type=chunk)[355](index=355&type=chunk) - The company is exposed to significant **foreign exchange risk** due to international operations, with fluctuations in currency exchange rates impacting financial results[356](index=356&type=chunk) - Employees, investigators, consultants, and partners may engage in misconduct, including non-compliance with regulations or fraud, leading to significant penalties, reputational harm, and operational disruptions[358](index=358&type=chunk) - The company faces potential **product liability claims** from clinical trials and commercial sales, which could result in substantial liability, costs, reputational damage, and delays in regulatory approval[359](index=359&type=chunk)[360](index=360&type=chunk)[361](index=361&type=chunk)[362](index=362&type=chunk) - Future success depends on retaining key senior management and attracting/motivating qualified personnel. Competition for talent is intense, and inability to do so could impede R&D and commercialization objectives[363](index=363&type=chunk)[364](index=364&type=chunk) - Expected significant growth in employees and operations (clinical development, regulatory, manufacturing, commercialization) may lead to difficulties in management, requiring improved systems and additional personnel, potentially disrupting operations[365](index=365&type=chunk)[366](index=366&type=chunk)[367](index=367&type=chunk) - The biopharmaceutical industry is highly competitive, with larger companies possessing greater resources. Failure to compete effectively on efficacy, safety, and convenience could materially harm the business[371](index=371&type=chunk)[372](index=372&type=chunk)[373](index=373&type=chunk)[374](index=374&type=chunk)[375](index=375&type=chunk)[376](index=376&type=chunk) [Risks Related to Intellectual Property](index=109&type=section&id=Risks%20Related%20to%20Intellectual%20Property) - Inability to obtain and maintain sufficient patent protection for its **T-win® platform** and product candidates, or if the scope is not broad enough, could allow competitors to commercialize similar products, adversely affecting the business[404](index=404&type=chunk)[406](index=406&type=chunk)[407](index=407&type=chunk)[408](index=408&type=chunk)[409](index=409&type=chunk)[411](index=411&type=chunk) - Reliance on trade secret protection for unpatentable know-how carries risks of disclosure or misappropriation, which could erode competitive position if competitors independently develop or gain access to such information[412](index=412&type=chunk)[440](index=440&type=chunk)[441](index=441&type=chunk) - Future intellectual property licenses may not be available on reasonable terms, or at all, potentially forcing the company to abandon development efforts or operate in a more costly manner[419](index=419&type=chunk) - Being sued for infringing third-party intellectual property rights could lead to costly and time-consuming litigation, prevent commercialization, or require expensive licenses, diverting resources and potentially harming the business[422](index=422&type=chunk)[423](index=423&type=chunk)[424](index=424&type=chunk)[425](index=425&type=chunk) - Changes in patent law (e.g., **Leahy-Smith Act**) or interpretations could diminish the value of patents, increasing uncertainties and costs for protecting inventions and enforcing rights[430](index=430&type=chunk)[431](index=431&type=chunk)[432](index=432&type=chunk) - Patent terms may be inadequate to protect product candidates for a sufficient time, leading to early competition from generics. Failure to obtain patent term extensions could shorten market exclusivity[434](index=434&type=chunk)[435](index=435&type=chunk) - Limited geographical patent protection means competitors can use technologies in unprotected countries and export infringing products, diminishing the value of intellectual property[436](index=436&type=chunk)[438](index=438&type=chunk)[439](index=439&type=chunk) [Risks Related to Our Common Stock](index=121&type=section&id=Risks%20Related%20to%20Our%20Common%20Stock) - The trading price of the common stock is highly volatile and can fluctuate widely due to factors like operating performance, clinical trial results, regulatory developments, and market conditions[447](index=447&type=chunk)[449](index=449&type=chunk) - Substantial sales of common stock, particularly by insiders or due to a large number of shares available for sale, could cause the stock price to decline[450](index=450&type=chunk) - Failure to maintain **Nasdaq listing requirements** (e.g., minimum bid price) could lead to delisting, reducing liquidity and market price, and potentially impacting the ability to raise capital[451](index=451&type=chunk) - Delaware law and company charter/bylaw provisions could discourage or delay a change of control, potentially depressing the stock price[452](index=452&type=chunk)[453](index=453&type=chunk) - Future sales and issuances of common stock or rights to purchase common stock, including through equity incentive plans or warrant exercises, could result in significant dilution for existing stockholders and cause the stock price to fall[458](index=458&type=chunk)[459](index=459&type=chunk)[460](index=460&type=chunk)[461](index=461&type=chunk) - The company does not intend to pay dividends, so investor returns will be limited to stock appreciation[462](index=462&type=chunk) - As an **'emerging growth company'** and **'smaller reporting company,'** reduced disclosure requirements may make the common shares less attractive to investors, potentially leading to lower trading volume and increased stock price volatility[463](index=463&type=chunk)[464](index=464&type=chunk)[465](index=465&type=chunk)[466](index=466&type=chunk)[467](index=467&type=chunk) [General Risk Factors](index=128&type=section&id=General%20Risk%20Factors) - Operating as a public company incurs significantly increased costs and requires substantial management time for compliance initiatives, including **Sarbanes-Oxley Act** requirements[468](index=468&type=chunk) - A **material weakness** in internal control over financial reporting (related to CRO accruals) could impair the ability to provide timely and reliable financial information, harming the business and stock price[469](index=469&type=chunk)[470](index=470&type=chunk)[471](index=471&type=chunk)[472](index=472&type=chunk)[473](index=473&type=chunk)[475](index=475&type=chunk) - Future changes in financial accounting standards or practices could cause adverse revenue fluctuations and affect reported results[480](index=480&type=chunk) - Changes in tax laws or regulations (e.g., **TCJA**, **IRA**) could adversely affect business operations, cash flow, and financial performance[481](index=481&type=chunk)[482](index=482&type=chunk) - Broad discretion in using existing cash and cash equivalents may not lead to effective use or increased share value[483](index=483&type=chunk) - Internal IT systems or those of third parties are vulnerable to security breaches, data loss, or other disruptions, which could materially disrupt development programs, compromise sensitive information, and expose the company to liability[484](index=484&type=chunk)[485](index=485&type=chunk)[486](index=486&type=chunk)[487](index=487&type=chunk) - Global operations expose the compa

[Introduction & Disclaimer](index=1&type=section&id=Introduction%20%26%20Disclaimer) This section outlines the standard disclaimer for forward-looking statements and presents the agenda for the conference call [Disclaimer & Forward-Looking Statements](index=2&type=section&id=Disclaimer%20%26%20Forward-Looking%20Statements) This section provides a standard disclaimer for forward-looking statements, highlighting inherent risks and uncertainties without guaranteeing future results - Forward-looking statements are based on current beliefs and expectations of management, involving risks, potential changes in circumstances, assumptions, and uncertainties[5](index=5&type=chunk) - Actual results and developments could be materially different from those expressed or implied by forward-looking statements due to known or unknown risks and uncertainties[5](index=5&type=chunk) [Agenda for Today's Call](index=3&type=section&id=Agenda%20for%20Today's%20Call) The agenda outlines the key topics to be discussed during the conference call, including an introduction, detailed Phase 3 data for Cylembio, an overview of the first-line advanced melanoma treatment landscape, and company milestones Agenda Topics | Topic | | :--- | | Introduction | | Cylembio Phase 3 Data | | First-line Advanced Melanoma Treatment Landscape | | Company Milestones | [Cylembio Overview & Phase 3 Results](index=4&type=section&id=Cylembio%20Overview%20%26%20Phase%203%20Results) This section provides an overview of Cylembio, presents its Phase 3 trial results, explains its mechanism of action, and details the company's pipeline [Cylembio Product Overview](index=4&type=section&id=Cylembio%20Product%20Overview) Cylembio (imsapepimut and etimupepimut, adjuvanted) is an investigational drug candidate for non-resectable/advanced melanoma, with Phase 3 results demonstrating clinical improvement - Cylembio is an investigational drug candidate that has not been approved for marketing by the US FDA or other regulatory authorities[9](index=9&type=chunk) - Cylembio in combination with pembrolizumab demonstrated clinical improvement across subgroups, with plans to engage with the FDA in Fall 2025 for potential BLA submission[11](index=11&type=chunk) Cylembio Phase 3 Topline Data | Metric | Cylembio + Pembrolizumab | Pembrolizumab Alone | | :--- | :--- | :--- | | Months mPFS | 19.4 | 11.0 | | HR (95% CI) | 0.77 (0.58-1.00) | | | p-value | 0.056* | | *Statistical significance threshold for this study was p=0.045 [Phase 3 Trial Topline Results](index=7&type=section&id=Phase%203%20Trial%20Topline%20Results) The Phase 3 trial for Cylembio plus pembrolizumab demonstrated improved median Progression-Free Survival, with notable benefits in specific subgroups and a favorable safety profile Phase 3 Trial Key Endpoints | Endpoint | Cylembio + Pembrolizumab | Pembrolizumab Alone | HR (95% CI) | p-value | | :--- | :--- | :--- | :--- | :--- | | Median PFS (ITT) | 19.4 months | 11.0 months | 0.77 (0.58-1.00) | 0.056* | | Median PFS (excl. prior anti-PD1) | 24.8 months | 11.0 months | 0.74 (0.56-0.98) | 0.037 (nominal) | | Median PFS (PD-L1 negative) | 16.6 months | 3.0 months | 0.54 (0.35-0.85) | 0.006 (nominal) | | Overall Survival (trend, not mature) | Favoring combination arm | | 0.79 (0.57, 1.10) | | *Statistical significance threshold for this study was p=0.045 - Cylembio demonstrated PFS benefit regardless of prespecified subgroups or stratification factors[17](index=17&type=chunk)[53](index=53&type=chunk) - The treatment was well-tolerated with no significant added systemic toxicity compared to pembrolizumab alone[17](index=17&type=chunk)[53](index=53&type=chunk) [Clinical Trial Design](index=11&type=section&id=Clinical%20Trial%20Design) This section details the Phase 3 clinical trial design, including patient enrollment, eligibility criteria, and primary and secondary endpoints - The Phase 3 clinical trial enrolled **407 patients** across over 100 sites in Europe, Australia, South Africa, Israel, and the US[28](index=28&type=chunk) - Eligibility criteria included advanced melanoma (unresectable stage III or metastatic stage IV) and measurable disease (RECIST 1.1)[28](index=28&type=chunk) - The primary endpoint was Progression-Free Survival (PFS) by central review, with secondary/exploratory endpoints including Overall Response Rate (ORR), Disease Control Rate (DCR), Overall Survival (OS), Duration of Response (DoR), and incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)[28](index=28&type=chunk) [Progression-Free Survival (PFS) Analysis](index=12&type=section&id=Progression-Free%20Survival%20(PFS)%20Analysis) This section presents the Progression-Free Survival analysis, highlighting the median PFS and early separation of treatment arms - PFS curves showed early separation at **3 months**, widening over time, indicating a sustained benefit for the Cylembio combination arm[30](index=30&type=chunk)[31](index=31&type=chunk) PFS Analysis Results | Arm | Median PFS (months) | Events | | :--- | :--- | :--- | | Cylembio + Pembro | 19.4 | 99 | | Pembro | 11.0 | 119 | | HR (95% CI) | 0.77 (0.58 to 1.00) | | | Log-rank p-value | 0.0558* | | *Statistical significance threshold for this study was p=0.045 [Baseline Characteristics & Subgroup Analysis](index=13&type=section&id=Baseline%20Characteristics%20%26%20Subgroup%20Analysis) This section analyzes baseline patient characteristics and consistent PFS improvements observed across various demographic and clinical subgroups - Baseline characteristics were balanced across treatment arms and reflected real-world melanoma patient populations[33](index=33&type=chunk)[34](index=34&type=chunk) - Consistent improvement in PFS was observed across the majority of subgroups, including age, disease stage, BRAF mutation status, PD-L1 status, geographical region, ECOG status, LDH levels, prior treatment, melanoma subtype, and baseline tumor size[35](index=35&type=chunk)[38](index=38&type=chunk)[41](index=41&type=chunk)[45](index=45&type=chunk) Subgroup Analysis of PFS | Subgroup | Cylembio + Pembro Events (Patients) | Pembro Events (Patients) | Unstratified HR (95% CI) | | :--- | :--- | :--- | :--- | | Overall | 99 (203) | 119 (204) | 0.77 [0.59; 1.01] | | PD-L1 Negative | 34 (67) | 49 (63) | **0.54 [0.35; 0.85]** | | PD-L1 Positive | 63 (129) | 63 (127) | 0.93 [0.65; 1.32] | | Excluding prior anti-PD1 exposure | N/A (mPFS **24.8 months**) | N/A (mPFS **11.0 months**) | **0.74 (0.56-0.98)** (nominal p=0.037) | | Excluding acral/mucosal patients | N/A (mPFS **22.1 months**) | N/A (mPFS **11.1 months**) | N/A | [Overall Survival (OS) Trend](index=20&type=section&id=Overall%20Survival%20(OS)%20Trend) This section presents the early, not yet mature, Overall Survival data, indicating a favorable trend for the Cylembio combination arm - Overall Survival (OS) data is not yet mature, but a trend favoring the Cylembio combination arm was observed, with early separation of survival curves that widened over time[48](index=48&type=chunk)[49](index=49&type=chunk) Overall Survival Trend | Arm | Events | Median OS (months) | | :--- | :--- | :--- | | IO + Pembro | 58 | 31.9 | | Pembro | 77 | N/A | | HR (95% CI) | 0.79 (0.57, 1.10) | | [Safety Data](index=21&type=section&id=Safety%20Data) This section provides safety data, demonstrating that Cylembio did not significantly increase systemic toxicity compared to monotherapy - Treatment with Cylembio did not add significant systemic toxicity compared to patients treated with pembrolizumab monotherapy[51](index=51&type=chunk) Safety Profile Comparison | Safety Metric | IO102-IO103 + Pembrolizumab (N=200) | Pembrolizumab (N=198) | | :--- | :--- | :--- | | Patients with AEs, n (%) | 194 (97.0) | 187 (94.4) | | Patients with treatment-related AEs, n (%) | 171 (85.5) | 161 (81.3) | | Patients with SAEs, n (%) | 64 (32.0) | 64 (32.3) | | Patients with treatment-related SAEs, n (%) | 19 (9.5) | 25 (12.6) | | Patients with AEs leading to death, n (%) | 4 (2.0) | 5 (2.5) | | Patients with immune-mediated AEs (imAE), n (%) | 68 (34.0) | 76 (38.4) | | Patients with injection site reactions, n (%) | 112 (56.0) | 2 (1.0) | [Mechanism of Action: T-win® Vaccine Platform](index=8&type=section&id=Mechanism%20of%20Action%3A%20T-win%C2%AE%20Vaccine%20Platform) IO Biotech's T-win® cancer vaccine platform activates T cells with a dual mechanism to target tumor and immune-suppressive cells, modulating the tumor micro-environment - The T-win® vaccine activates T cells with a dual mechanism to attack both target-expressing tumor cells and immune-suppressive cells (e.g., IDO1, PD-L1)[20](index=20&type=chunk) - The platform aims to provide a new therapeutic strategy with the potential to improve outcomes for cancer patients by killing tumor cells and turning the tumor micro-environment hostile to cancer[21](index=21&type=chunk) [Pipeline Overview](index=9&type=section&id=Pipeline%20Overview) IO Biotech's pipeline includes three T-win® product candidates in various clinical phases for multiple cancer indications, alongside preclinical candidates IO Biotech Pipeline | Product Candidates | Targets | Line of therapy/indication | Phase | Takeaways & next steps | | :--- | :--- | :--- | :--- | :--- | | Cylembio® (IOB-013) | IDO1, PD-L1 | First Line Advanced Melanoma | Phase 3 | Demonstrates clinical improvement in mPFS, narrowly missed statistical significance. Plans to discuss data with FDA in Fall 2025; potential US BLA submission | | Cylembio® (IOB-022) | IDO1, PD-L1 | First Line Solid Tumors (Lung (NSCLC), Head & Neck (SCCHN)) | Phase 2 | SCCHN: Primary endpoint met. NSCLC: Encouraging data | | Cylembio® (IOB-032) | IDO1, PD-L1 | Neoadjuvant / Adjuvant Solid Tumors (Melanoma, Head & Neck (SCCHN)) | Phase 2 | Enrollment completed in 2025. Initial data in 2H25 | | IO112 | Arginase 1 | Solid Tumors (Indications TBD) | Pre-clinical | Next pipeline candidate expected to enter clinical development | | IO170 | TGF-B1 | Solid Tumors (Indications TBD) | Pre-clinical | Early-stage pipeline candidate | [Advanced Melanoma Treatment Landscape](index=23&type=section&id=Advanced%20Melanoma%20Treatment%20Landscape) This section analyzes the advanced melanoma treatment landscape, including patient needs, market opportunity, and competitive positioning [Melanoma Patient Journey & Unmet Needs](index=6&type=section&id=Melanoma%20Patient%20Journey%20%26%20Unmet%20Needs) This section highlights the significant unmet medical needs in unresectable or metastatic melanoma due to current treatment limitations - Unresectable or Metastatic Melanoma affects **~15,000 patients annually** in the U.S., representing a high unmet medical need due to lack of efficacy and toxicity issues with available standard of care[14](index=14&type=chunk) - Cylembio, if approved, has the potential to address this high unmet medical need by providing patients and healthcare professionals with a new treatment option[14](index=14&type=chunk) [Market Opportunity & Forecast](index=24&type=section&id=Market%20Opportunity%20%26%20Forecast) This section details the growing global melanoma market, driven by increasing incidence and a high unmet need for more effective therapies - Melanoma incidence is increasing globally, with **~331,000 patients newly diagnosed** and **~58,000 patient deaths annually**[56](index=56&type=chunk) - The 5-year survival rate for patients in stage IV is **30%**, and **~50% of patients progress within one year** of treatment, indicating a significant unmet need for more effective options[56](index=56&type=chunk)[58](index=58&type=chunk) Melanoma Drug Sales Forecast | Metric | 2024 (USD billions) | 2030 (USD billions) | CAGR | | :--- | :--- | :--- | :--- | | US Melanoma Drug Sales | 8.4 | 13.2 | +9% | | Global Melanoma Drug Sales | 9.4 | 14 | | [Competitive Landscape](index=25&type=section&id=Competitive%20Landscape) This section positions Cylembio favorably within the first-line advanced melanoma market, acknowledging the caveats of cross-trial comparisons - If approved, Cylembio would be well-positioned for the treatment of first-line advanced melanoma[59](index=59&type=chunk) Median PFS Comparison of Therapies | Drug (Combination) | Median PFS | | :--- | :--- | | Cylembio + Pembro | **19.4m** | | Pembro (KN-006) | 11.6m | | Opdualag (Nivo+Rela) | 10.2m | | Ipi/Nivo (CM-067) | 11.5m | | Nivo | 4.6m | | Ipi | 6.9m | - Comparisons across clinical trials should be interpreted with caution due to differences in study design, patient populations, endpoints, and other factors[60](index=60&type=chunk) [Company Milestones & Financials](index=26&type=section&id=Company%20Milestones%20%26%20Financials) This section outlines key company milestones, including regulatory plans and pipeline advancements, alongside its current financial position [Key Milestones](index=27&type=section&id=Key%20Milestones) This section details anticipated key milestones through 2026, encompassing regulatory submissions, clinical data readouts, and preclinical candidate advancements - Discussions with FDA for Cylembio (1L Advanced Melanoma) are planned for **Fall 2025**, with potential US BLA submission and launch thereafter[63](index=63&type=chunk) - Potential EU Marketing Authorization Application (MAA) submission for Cylembio (1L Advanced Melanoma) is expected in **2026**[63](index=63&type=chunk) - Initial data from Cylembio's neoadjuvant/adjuvant Phase 2 cohorts is expected in **H2 2025**, with final data from first-line Phase 2 for NSCLC and SCCHN also anticipated[63](index=63&type=chunk) - IND submission for IO112 (Solid Tumors) and IND enabling studies for IO170 (Solid Tumors) are planned for **2026**[63](index=63&type=chunk) [Financial Position](index=27&type=section&id=Financial%20Position) The company maintains a cash runway into Q1 2026, supported by its Q2 cash balance and a recent EIB loan tranche - Cash position extends into **Q1 2026**[62](index=62&type=chunk) Financial Metrics | Metric | Value | | :--- | :--- | | Q2 Cash Balance | **$28 million** | | EIB Loan | Second tranche received on **July 4, 2025** |