8-K
IO Biotech, Inc. (IOBTQ)
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(D)
OF THE SECURITIES EXCHANGE ACT OF 1934
Date of Report (Date of earliest event reported): August 11, 2025
IO BIOTECH, INC.
(Exact name of Registrant as Specified in its Charter)
| Delaware | 001-41008 | 87-0909276 |
|---|---|---|
| (State or other jurisdiction<br>of incorporation) | (Commission<br>File Number) | (IRS Employer<br>Identification No.) |
| Ole Maaløes Vej 3 | ||
| --- | ||
| DK-2200 Copenhagen N | ||
| Denmark | ||
| (Address of principal executive offices) (Zip Code) |
Registrant’s telephone number, including area code: +45 7070 2980
N/A
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ☐ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
|---|---|
| ☐ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| --- | --- |
| ☐ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| --- | --- |
| ☐ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
| --- | --- |
Securities registered pursuant to Section 12(b) of the Act:
| Title of each class | Trading<br>Symbol(s) | Name of each exchange<br>on which registered |
|---|---|---|
| Common Stock, par value $0.001 per share | IOBT | The Nasdaq Stock Market LLC |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 2.02. | Results of Operations and Financial Condition. |
|---|
As discussed below, IO Biotech, Inc., a Delaware corporation (the “Company”), is hosting a conference call and webcast, during which the Company will make a slide presentation. In the slide presentation, the Company is disclosing an estimated cash and cash equivalents balance of approximately $28.1 million as of June 30, 2025, and further disclosing that the Company estimates that these cash and cash equivalents, plus the €12.5 million drawn on July 4, 2025 from the second tranche of the term loan facility with the European Investment Bank, will be sufficient to meet its working capital requirements into the first quarter of 2026.
Because the Company’s financial closing procedures as of and for the six months ended June 30, 2025, are not yet complete, its final results upon completion of those procedures may differ materially from its preliminary estimate. Accordingly, you should not place undue reliance on this preliminary estimate.
| Item 7.01. | Regulation FD Disclosure. |
|---|
On August 11, 2025, the Company issued a press release announcing topline results from IOB-013, the Company’s Phase 3 trial of Cylembio® in combination with pembrolizumab as a first-line treatment for patients with unresectable or metastatic (advanced) melanoma. The Company is hosting a conference call and webcast at 8:30 am Eastern Time, on August 11, 2025, during which the Company will discuss the topline results and will make a slide presentation.
The press release is attached as Exhibit 99.1 and the form of slide presentation is attached as Exhibit 99.2, and each is incorporated into this Item 8.01 by reference.
The information contained in this Current Report on Form 8-K is being furnished and shall not be deemed to be “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section and shall not be incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as shall be expressly set forth by specific reference in such filing.
| Item 8.01. | Other Events |
|---|
The randomized, open-label study enrolled 407 patients across more than 100 sites worldwide. Patients received either Cylembio in combination with pembrolizumab (n=203) or pembrolizumab alone (n=204). The primary endpoint was PFS as assessed by a blinded independent review committee per RECIST v1.1. The early and sustained separation of PFS curves demonstrated an improvement with a hazard ratio of 0.77 [95% CI: 0.58-1.00; p=0.056; threshold for significance p≤0.045]. Based on an intent-to-treat analysis, patients in the study treated with Cylembio in combination with pembrolizumab achieved 19.4 months of median progression free survival compared to 11.0 months in patients treated with pembrolizumab alone. Although not yet mature, a trend toward an improvement in overall survival was also observed [HR 0.79 (95% CI: 0.57-1.10)]; the company expects OS to mature over the next six to nine months. Improvement in PFS was achieved across virtually all subgroups, including those with poor prognostic factors, with a profound effect in patients with PD-L1 negative tumors treated with Cylembio plus pembrolizumab (n=67) compared to patients treated with pembrolizumab monotherapy (n=63), HR: 0.54 (CI 0.35-0.85) (nominal p=0.006), with mPFS of 16.6 months vs. 3.0 months, respectively. Additionally, in a post hoc analysis of patients enrolled in this study without prior anti-PD-1 treatment (n=371), patients treated with Cylembio plus pembrolizumab achieved improvement in PFS compared to patients treated with pembrolizumab monotherapy, HR: 0.74 (CI 0.56-0.98) (nominal p=0.037), with mPFS of 24.8 months vs. 11.0 months, respectively. The combination was well tolerated, with no new safety signals observed. Injection site reactions, which were transient and resolved on treatment, were the most commonly reported adverse events in the combination arm, with 56% of patients receiving Cylembio plus pembrolizumab reporting an event. Based on these results, the Company plans to meet with the regulatory authorities to discuss the totality of data and determine next steps for submission of a Biologics License Application (BLA) for the treatment of advanced melanoma to the U.S. Food and Drug Administration (FDA). Additionally, the Company plans to present more detailed results from the IOB-013 study at an upcoming medical meeting.
| Item 9.01. | Financial Statements and Exhibits. |
|---|
(d) Exhibits
| Exhibit<br> <br>Number | Exhibit Description |
|---|---|
| 99.1 | IO Biotech, Inc. Press Release, dated as of August 11, 2025 |
| 99.2 | IO Biotech, Inc. Presentation |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document) |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| IO BIOTECH, INC. | ||
|---|---|---|
| Date: August 11, 2025 | By: | /s/ Mai-Britt Zocca, Ph.D. |
| Name: | Mai-Britt Zocca, Ph.D. | |
| Title: | Chief Executive Officer |
EX-99.1
Exhibit 99.1
IO Biotech Announces Clinical Improvement in Progression Free Survival Demonstrated in Pivotal Phase 3Trial of Cylembio^®^ plus KEYTRUDA^®^ (Pembrolizumab) **** for the Treatment of First-line Advanced Melanoma, butStatistical Significance Narrowly Missed
| • | Patients treated with Cylembio (imsapepimut and etimupepimut, adjuvanted) plus pembrolizumab achievedimprovement in progression free survival (PFS) compared to patients treated with pembrolizumab monotherapy, HR=0.77 (CI 0.58-1.00), (p=0.056), with median PFS (mPFS) of 19.4 months vs. 11.0 months,respectively; the results on the primary endpoint narrowly missed the study’s statistical significance threshold of p≤0.045 |
|---|---|
| • | In patients enrolled in this study without prior neo-adjuvant/adjuvantanti-PD-1 treatment (n=371), patients treated with Cylembio plus pembrolizumab achieved improvement in PFS, HR: 0.74 (CI0.56-0.98) (nominal p=0.037), with mPFS of 24.8 months vs. 11.0 months for the control arm |
| --- | --- |
| • | Improvement in PFS was achieved across virtually all subgroups, including those with poor prognosticfactors |
| --- | --- |
| • | A profound effect was observed in patients with PD-L1 negative tumorstreated with Cylembio plus pembrolizumab, HR: 0.54 (CI 0.35-0.85) (nominal p=0.006), with mPFS of 16.6 months vs. 3.0 months for the control arm |
| --- | --- |
| • | A trend towards improvement in overall survival (OS) was observed in patients treated with Cylembio pluspembrolizumab (OS not yet mature), HR=0.79 (CI 0.57-1.10) |
| --- | --- |
| • | Cylembio plus pembrolizumab was well tolerated, with no new safety signals observed |
| --- | --- |
| • | IO Biotech plans to meet with the FDA this fall to discuss the data and next steps for a potential regulatorysubmission |
| --- | --- |
| • | Company to host conference call today at 8:30 a.m. ET to discuss these results |
| --- | --- |
New York, NY – August 11, 2025: IO Biotech (Nasdaq: IOBT) today announces topline results from the pivotal Phase 3 trial of its investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine, Cylembio^®^ (imsapepimut and etimupepimut, adjuvanted). The trial evaluated Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA^®^ (pembrolizumab), vs. pembrolizumab alone as a first-line treatment in 407 patients with unresectable or metastatic (advanced) melanoma. In the study, Cylembio plus pembrolizumab demonstrated clinical improvement in progression free survival compared to pembrolizumab alone, but statistical significance was narrowly missed on the primary endpoint.
“In this study, we observed a highly encouraging improvement in progression free survival and consistent trend in overall survival in patients treated with Cylembio,” said Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech. “The magnitude and durability of clinical effect observed consistently across subgroups supports our confidence in Cylembio and its potential as a treatment for advanced melanoma patients. We look forward to engaging with the FDA to determine a potential path to approval based on these data.”
The randomized, open-label study enrolled 407 patients across more than 100 sites worldwide. Patients received either Cylembio in combination with pembrolizumab (n=203) or pembrolizumab alone (n=204). The primary endpoint was PFS as assessed by a blinded independent review committee per RECIST v1.1. The early and sustained separation of PFS curves demonstrated an improvement with a hazard ratio of 0.77 [95% CI: 0.58-1.00; p=0.056; threshold for significance p≤0.045]. Based on an intent-to-treat analysis, patients in the study treated with Cylembio in combination with pembrolizumab achieved 19.4 months of median progression free survival compared to 11.0 months in patients treated with pembrolizumab alone.
1
Although not yet mature, a trend toward an improvement in overall survival was also observed [HR 0.79 (95% CI: 0.57-1.10)]; the company expects OS to mature over the next six to nine months.
Improvement in PFS was achieved across virtually all subgroups, including those with poor prognostic factors, with a profound effect in patients with PD-L1 negative tumors treated with Cylembio plus pembrolizumab (n=67) compared to patients treated with pembrolizumab monotherapy (n=63), HR: 0.54 (CI 0.35-0.85) (nominal p=0.006), with mPFS of 16.6 months vs. 3.0 months, respectively. Additionally, in a post hoc analysis of patients enrolled in this study without prior anti-PD-1 treatment (n=371), patients treated with Cylembio plus pembrolizumab achieved improvement in PFS compared to patients treated with pembrolizumab monotherapy, HR: 0.74 (CI 0.56-0.98) (nominal p=0.037), with mPFS of 24.8 months vs. 11.0 months, respectively.
The combination was well tolerated, with no new safety signals observed. Injection site reactions, which were transient and resolved on treatment, were the most commonly reported adverse events in the combination arm, with 56% of patients receiving Cylembio plus pembrolizumab reporting an event.
“In this study, patients treated with Cylembio in combination with pembrolizumab have achieved the longest median PFS ever observed in a Phase 3 clinical study in advanced melanoma, and in the PD-L1 negative population, patients achieved a remarkable 16.6 months of median PFS, compared to 3.0 months in patients treated with pembrolizumab alone,” said Omid Hamid, MD, Director, Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate. “The significant benefit seen across patients with poor prognostic factors, including PD-L1 negative patients, cannot be overlooked. Given the notable safety profile and the strong clinical effect observed with Cylembio, as well as the unmet need in advanced melanoma patients, Cylembio, if approved, has the potential to become a new standard of care for patients with advanced melanoma.”
“These data show the potential of a therapeutic cancer vaccine in patients with metastatic melanoma,” said Jessica Hassel, MD, Professor at the Department of Dermatology and National Center for Tumor Diseases at the University Hospital Heidelberg, Germany, and lead enrolling investigator for the Phase 3 trial. “We were thrilled to play such an important part in this study and to have had the ability to offer our patients an investigational therapy that potentially offers improvements in PFS while not adding significant systemic toxicity.”
“Delaying progression and improving survival is the ultimate treatment goal for patients and although overall survival is not yet mature, the trend we are seeing in OS with separation of the curves is encouraging, with a consistent PFS clinical improvement and OS trend favoring the combination arm across virtually all subgroups, with no new safety signals or significant additional systemic toxicity,” said Qasim Ahmad, MD, chief medical officer of IO Biotech. “We are deeply grateful to the patients for their participation in this study, as well as to investigators and study coordinators whose dedication and collaboration brings us one step closer to delivering a new treatment option to patients in need.”
“Since reporting the positive outcome of our Phase 1/2 study (MM1636) in a similar patient population, we have been eagerly awaiting these results supporting the activity of Cylembio combined with an anti-PD-1 in patients with advanced melanoma,” said Inge Marie Svane, MD, PhD, Professor, Director of the National Center for Cancer Immune Therapy (CCIT) at the Copenhagen University Hospital, Herlev and Principal Investigator in the Phase 3 trial. “These data provide evidence that a therapeutic cancer vaccine can improve progression free survival in patients with metastatic disease.”
Based on these results, IO Biotech plans to meet with the United States (US) Food and Drug Administration (FDA) this fall to discuss the totality of data and determine next steps for submission of a Biologics License Application (BLA) for the treatment of advanced melanoma. Additionally, the company plans to present more detailed results from the IOB-013 study at an upcoming medical meeting.
2
Conference Call and Webcast Information
IO Biotech management will hold a conference call and webcast today at 8:30 a.m. ET to discuss these clinical data results. Participants can register for the live webcast here. The live webcast and replay will be available through IO Biotech’s website here.
About the IOB-013/KN-D18 Pivotal Phase 3 Clinical Trial
IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) was an open label, randomized Phase 3 pivotal clinical trial evaluating Cylembio^®^ in combination with Merck’s anti-PD-1 therapy, KEYTRUDA^®^ (pembrolizumab) versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. Enrollment in the trial was completed by December 2023 with a total of 407 patients enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study was progression free survival. Secondary endpoints include overall response rate, overall survival, durable objective response rate, complete response rate, duration of response, time to complete response, disease control rate, and incidence of adverse events and serious adverse events (safety and tolerability). Biomarkers in the blood and tumor tissue will also be assessed as exploratory endpoints. The company reported topline results from this trial in the third quarter of 2025. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab.
About Cylembio^®^
Cylembio^®^ (imsapepimut and etimupepimut, adjuvanted) is an investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine candidate designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase 1 (IDO1) positive and/or programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating Cylembio in combination with Merck’s anti-PD-1 therapy, KEYTRUDA^®^ (pembrolizumab) versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating Cylembio in combination with pembrolizumab as first line treatment in patients with advanced solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating Cylembio in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. Enrollment in the Phase 3 trial was completed rapidly by December 2023 with topline results from this trial reported in the third quarter of 2025. Enrollment in the two ongoing company-sponsored Phase 2 clinical trials is now complete.
The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck, which is supplying pembrolizumab. IO Biotech maintains global commercial rights to Cylembio.
Cylembio^®^ is a registered trademark of IO Biotech ApS, a subsidiary of IO Biotech.
KEYTRUDA^®^ is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (known as MSD outside of the US and Canada).
About IO Biotech
IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines based on its T-win^®^ platform. The T-win platform is based on a novel approach to cancer vaccines designed to activate T cells to target both tumor cells and the immune-suppressive cells in the tumor microenvironment. IO Biotech is advancing its lead cancer vaccine candidate, Cylembio^®^, in clinical trials, and additional pipeline candidates through preclinical development. IO Biotech is headquartered in Copenhagen, Denmark and has US headquarters in New York, New York.
3
For further information, please visit www.iobiotech.com. Follow us on our social media channels on LinkedIn and X (@IOBiotech).
Forward-Looking Statement
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements, including statements regarding the timing or outcome of communications with the FDA, submission of a BLA, the launch of Cylembio, and statements regarding other current or future clinical trials, their progress, enrollment or results, or the company’s financial position or cash runway, are based on IO Biotech’s current assumptions and expectations of future events and trends, which affect or may affect its business, strategy, operations or financial performance, and actual results and other events may differ materially from those expressed or implied in such statements due to numerous risks and uncertainties. Forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified. Because forward-looking statements are inherently subject to risks and uncertainties, you should not rely on these forward-looking statements as predictions of future events. These forward-looking statements speak only as of the date hereof and should not be unduly relied upon. Except to the extent required by law, IO Biotech undertakes no obligation to update these statements, whether as a result of any new information, future developments or otherwise.
Contacts:
Investors
Maryann Cimino, Director of Investor Relations
IO Biotech, Inc.
617-710-7305
mci@iobiotech.com
Media
Julie Funesti
Edelman
917-498-1967
julie.funesti@edelman.com
4
EX-99.2
Breaking Boundaries. Igniting Change. IO Biotech Conference Call Pivotal Phase 3 Trial Results 11August2025 Exhibit 99.2
DISCLAIMER | Forward Looking Statements Certain information contained in this presentation includes “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, related to our business plan, clinical trials and regulatory submissions. We may, in some cases, use terms such as “may,” “should,” “would,” “expects,” “plans,” “anticipates,” “could,” “intends,” “target,” “projects,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or other words that convey uncertainty of the future events or outcomes to identify these forward-looking statements. Our forward-looking statements are based on current beliefs and expectations of our management team that involve risks, potential changes in circumstances, assumptions, and uncertainties. Any or all of the forward-looking statements may turn out to be wrong or be affected by inaccurate assumptions we might make or by known or unknown risks and uncertainties. These forward-looking statements are subject to risks and uncertainties including risks related to the execution of our business plan, success and timing of our clinical trials or other studies and the other risks set forth in our filings with the U.S. Securities and Exchange Commission. For all these reasons, actual results and developments could be materially different from those expressed in or implied by our forward-looking statements. You are cautioned not to place undue reliance on these forward-looking statements, which are made only as of the date of this presentation. We undertake no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstances, except as required by law.
Agenda for Today’s Call Topic Speaker Introduction Mai-Britt Zocca, Ph.D., chief executive officer Cylembio Phase 3 Data Qasim Ahmad, M.D., chief medical officer First-line Advanced Melanoma Treatment Landscape Omid Hamid, MD, Director, Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate Company Milestones Amy Sullivan, chief financial officer
Cylembio is an investigational drug candidate that has not been approved for marketing by the US FDA or other regulatory authorities.
IO Biotech | Breaking boundaries. Igniting change of patients progress within one year of treatment 2025 Discuss path forward with FDA, potentially submit BLA PHASE 3 RESULTS * Statistical significance threshold for this study was p=0.045. 1. https://gco.iarc.fr/today/en/; 2. https://seer.cancer.gov/statfacts/html/melan.html; 3. Melanoma Research Alliance; 4. Larkin et al. N Engl J Med 2019;381:1535-1546; 5. Robert et al. Lancet Oncol 2019;20:1239-1251; 6. Tawbi et al. N Engl J Med 2022;386:24-34; 7. Weber et al. Oncologist. 2016;21(10):1230-1240; 8. Evaluate Pharma 2025 Cylembio in combination with pembrolizumab demonstrated clinical improvement across subgroups; company plans to engage with the FDA in Fall 2025 SCALABILITY OPPORTUNITY Improved clinical effect observed without significant added systemic toxicity vs. pembro alone 19.4 vs. 11.0 Months mPFS HR=0.77 (CI 0.58-1.00) (p=0.056)* PFS improvement observed regardless of prespecified subgroups or stratification factors 15,000 Demonstrated clinical improvement; Narrowly missed statistical significance Cylembio data across indications (Melanoma, SCCHN, NSCLC), with pipeline potentially addressing other difficult to treat cancers US patients with non-resectable / advanced melanoma 50% $5.6 billion US market opportunity growing at 9% Global supply chain and distribution in place; manufacturing at commercial scale with well-established CDMOs 3
- Melanoma of the Skin — Cancer Stat Facts; 2. https://seer.cancer.gov/statfacts/html/melan.html; Bajaj. J Natl Cancer Inst. 2020; Leeneman. EJC. 2021; Zhang. Adv Ther. 2023; Eggermont. J of Clin Onc. 2019; Eggermont. NEJM. 2022; Wolchok. J Clin Oncol. 2022; Miller, CA Cancer J Clin, 2019; National Comprehensive Cancer Network (NCCN): Clinical Practice Guidelines in Oncology (NCCN Guidelines®); Melanoma Version 2.2025 THE MELANOMA PATIENT JOURNEY 1 Disease Presentation Primary Care Physician or Dermatologist 2 Diagnosis & Referral Newly Diagnosed Melanoma in ~100,0001 patients annually in the U.S. 3 Resectable Melanoma ~92,000 patients2 Surgical candidate? Residual Disease Post-Surgery? Neo/adjuvant treatment and Surgical Resection 4 Unresectable or Metastatic Melanoma ~15,000 patients2: High unmet medical need still exists due to lack of efficacy and toxicity issues from available SOC 1L Treatment Selection, Insurance and Access (anti-PD1 monotherapy; anti PD1 combination with either anti-CTLA4 or anti LAG3 agents) Patient Checks in at the Infusion Center Product Preparation & Delivery to Infusion Center Product Administration Yes No Yes Cylembio, if approved, has the potential to address a high unmet medical need providing patients and HCPs a new treatment option.
PHASE 3 TRIAL | Topline results Cylembio demonstrated PFS benefit regardless of prespecified subgroups or stratification factors Median progression free survival, ITT analysis: Cylembio plus pembrolizumab 19.4 months vs. 11.0 months for patients treated with pembrolizumab alone, HR=0.77 (CI 0.58-1.00) (p=0.056)* Overall Survival trend favoring Cylembio combination arm, OS not yet mature HR = 0.79 (CI 0.57, 1.10) Well-tolerated with no significant added systemic toxicity compared to pembrolizumab alone * Statistical significance threshold for this study was p=0.045. **Post-hoc analysis. Source: Data on file. In PD-L1 negative group, mPFS was 16.6 months in patients treated with Cylembio plus pembrolizumab compared to 3.0 months in patients treated with pembro alone, HR: 0.54 (CI 0.35-0.85) (nominal p=0.006) Per phase 1/2 trial population, excluding patients with prior anti-PD1 exposure** (n=36): mPFS was 24.8 months vs. 11.0 months HR: 0.74 (CI 0.56-0.98) (nominal p=0.037) (n=371)
MECHANISM OF ACTION | IO Biotech’s T-win® vaccine approach supported by improvement in mPFS demonstrated with Cylembio in Phase 3 Subcutaneous injection with T-win® therapeutic cancer vaccine T-win vaccine activates T cells with a dual mechanism of action T cells attack both target expressing tumor cells and immune-suppressive cells (e.g., IDO1, PD-L1) The modulated and inflamed TME becomes immune permissive, enabling further tumor cell killing by the T cells IO Biotech’s T-win cancer vaccine platform is designed to provide a new therapeutic strategy with the potential to improve outcomes for patients with cancer by killing tumor cells and turning the tumor micro-environment hostile to cancer cells Kjeldsen JW, et al. Nat Med 2021;27:2212–23. Erratum in: Nat Med 2022;28:871; Munir S, et al. PLoS One 2012;7:e34568; Munir S, et al. Oncoimmunology 2013;2:e23991; Ahmad SM, et al. Blood Cancer J 2014;4:e230; Andersen MH. Semin Immunopathol 2019;41:87–95; IO Biotech and Lankenau Institute (unpublished data); Andersen MH, et al. Semin Immunopathol 2023;45:253–64.
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* Cylembio demonstrates clinical improvement in mPFS, narrow miss on statistical significance Plans to discuss data with FDA in Fall 2025; potential US BLA submission IO102–IO103 IOB-022: First Line Solid Tumors* Lung (NSCLC) Head & Neck (SCCHN) SCCHN: Primary endpoint met NSCLC: Encouraging data IOB-032: Neoadjuvant / Adjuvant Solid Tumors* Melanoma Head & Neck (SCCHN) Enrollment completed in January 2025 Initial data in 2H25 IO112 Target: Arginase 1 Solid Tumors Indications TBD Next pipeline candidate expected to enter clinical development IO170 Target:TGF-b1 Solid Tumors Indications TBD Early-stage pipeline candidate PIPELINE | 3 T-win product candidates being evaluated in multiple cancer indications Cylembio® (imsapepimut and etimupepimut, adjuvanted) * In combination with pembrolizumab; NSCLC, non-small cell lung cancer, PFS, progression-free survival; SCCHN, squamous cell carcinoma of the head and neck; IOB-013: ClinicalTrials.gov: NCT05155254; IOB-022: ClinicalTrials.gov: NCT05077709; IOB-032: ClinicalTrials.gov: NCT05280314
Cylembio Phase 3 Pivotal Trial Results
Primary endpoint PFS by central review Secondary/exploratory endpoints ORR, DRR, CRR, OS, DoR, TTR, DCR Incidence of AEs and SAEs Quality of life Biomarkers in blood and tumor tissue will also be assessed Stratification Endpoints Randomization 407 enrolled across >100 sites in Europe, Australia, South Africa, Israel and the US Advanced melanoma Unresectable stage III Metastatic stage IV > 6 months after neoadjuvant/ adjuvant anti-PD-1 Measurable disease (RECIST 1.1) ECOG performance status 0-1 Stable CNS disease is allowed Eligibility criteria PHASE 3 CLINICAL TRIAL DESIGN 1L, first-line; AE, adverse event; BLA, Biologics License Application; CNS, central nervous system; CRR, complete response rate; DCR, disease control rate; DoR, duration of response; DRR, durable response rate; ECOG, Eastern Cooperative Oncology Group; IA, interim analysis; IDMC, independent data monitoring committee; mut, mutation; ORR, objective response rate; OS, overall survival; PD-1, programmed cell death protein 1; PFS, progression-free survival; ph, phase; q3w, once every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; SAE, serious adverse event; TTR, time to response; WT, wild-type. ClinicalTrials.gov: NCT05155254. Disease Stage (Low vs high risk)* BRAF (mut vs WT) *Stage III and IV M1a-b vs. stage IV M1c-d IO102-IO103 and Pembrolizumab 200mg q3w N= 203 Pembrolizumab 200mg q3w N=204 1:1 Clinical trial design Patients in both arms can be treated for up to 2 years
PHASE 3 TRIAL | Early separation of PFS curves at 3 months – widening over time PFS primary analysis by blinded independent review committee (stratified by PD-L1 and Disease Stage) Median PFS: Cylembio + Pembro: 19.4 months Pembro: 11.0 months Marginally missed statistical significance: HR = 0.77 (0.58, 1.00) Logrank test p-value = 0.0558* *Statistical significance threshold for this study was p=0.045. Source: Company data on file.
IO102-IO103 + Pembro N (%) Pembrolizumab N (%) IO102-IO103 + Pembro N (%) Pembrolizumab N (%) Age [years] Region, n (%) n 203 204 USA 7 (3.4) 10 (4.9) Mean (SD) 67.5 (13.71) 67.7 (12.96) ROW 196 (96.6) 194 (95.1) Median (Q1, Q3) 71.0 (59.0, 78.0) 69.0 (60.0, 78.0) Weight [kg] Min, Max 28, 88 22, 91 n 203 204 Age group, n (%) Mean (SD) 82.1 (17.61) 78.5 (15.70) <65 years 78 (38.4) 77 (37.7) Median (Q1, Q3) 80.0 (71.0, 93.0) 77.5 (69.0, 88.5) >=65 and <75 years 49 (24.1) 56 (27.5) Min, Max 48, 143 45, 128 >=75 years 76 (37.4) 71 (34.8) Randomization stratification (IXRS) – Disease stage at baseline, n (%) Sex, n (%) Stage III (unresectable) or stage IV M1a-b 123 (60.6) 123 (60.3) Female 67 (33.0) 84 (41.2) Stage IV M1c-d 80 (39.4) 81 (39.7) Male 136 (67.0) 120 (58.8) Randomization stratification (IXRS)- B-RAFV600 mutation status, n (%) Race, n (%) Mutated 84 (41.4) 83 (40.7) White 196 (96.6) 191 (93.6) Wild type 119 (58.6) 121 (59.3) Other 5 (2.5) 10 (4.9) Baseline disease stage (EDC), n (%) Not Reported/Unknown 2 (1.0) 3 (1.5) Stage III (unresectable) 26 (12.8) 21 (10.3) Ethnicity, n (%) Stage IV M1a 34 (16.7) 41 (20.1) Hispanic or Latino 9 (4.4) 4 (2.0) Stage IV M1b 61 (30.0) 61 (29.9) Not Hispanic or Latino 180 (88.7) 177 (86.8) Stage IV M1c 75 (36.9) 75 (36.8) Not Reported/Unknown 14 (6.9) 23 (11.3) Stage IV M1d 7 (3.4) 6 (2.9) Confidential PHASE 3 TRIAL | Baseline characteristics balanced across treatment arms and reflect real world melanoma patients (1 of 2)
IO102-IO103 + Pembro N (%) Pembrolizumab N (%) IO102-IO103 + Pembro N (%) Pembrolizumab N (%) PD-L1, n (%) Prior melanoma systemic anti-cancer therapy, n (%) Positive (MEL score >=2) 129 (63.5) 127 (62.3) Anti PD-1/PD-L1 15 ( 7.4) 21 (10.3) Negative (MEL score =0, 1) 67 (33.0) 63 (30.9) BRAF/MEK inhibitors 9 ( 4.4) 3 ( 1.5) Not available 7 (3.4) 14 (6.9) Chemotherapy, hormonal therapy, other biological or targeted therapies 5 ( 2.5) 11 ( 5.4) ECOG performance status, n (%) No prior treatment 175 (86.2) 171 (83.8) 0 149 (73.4) 159 (77.9) Melanoma subtype, n (%) 1 54 (26.6) 45 (22.1) Cutaneous 177 (87.2) 174 (85.3) LDH [U/L] Mucosal 4 (2.0) 11 (5.4) n 203 203 Acral 6 (3.0) 3 (1.5) Mean (SD) 272.2 (193.17) 269.1 (226.93) Unknown primary melanoma or other 16 (7.9) 16 (7.8) Median (Q1, Q3) 213.0 (177.0, 284.0) 209.0 (175.0, 264.0) Baseline tumor burden [mm] Min, Max 112, 1749 100, 2384 n 200 203 LDH level group 1, n (%) Mean (SD) 66.2 (59.84) 59.7 (46.76) ≤ULN 133 (65.5) 131 (64.2) Median (Q1, Q3) 51.5 (28.0, 84.5) 46.0 (30.0, 76.0) >ULN 70 (34.5) 72 (35.3) Min, Max 7, 414 10, 278 Missing 0 1 (0.5) Baseline tumor burden group, n (%) LDH level group 2, n (%) <100 mm 167 (82.3) 179 (87.7) ≤2xULN 189 (93.1) 190 (93.1) ≥100 mm 33 (16.3) 24 (11.8) >2xULN 14 (6.9) 13 (6.4) Missing 3 (1.5) 1 (0.5) Missing 0 1 (0.5) Liver metastases, n (%) Yes 42 (20.7) 37 (18.1) No 161 (79.3) 167 (81.9) PHASE 3 TRIAL | Baseline characteristics balanced across treatment arms and reflect real world melanoma patients (2 of 2)
PHASE 3 TRIAL | Baseline characteristics balanced across treatment arms and reflect real world melanoma patients (1 of 2) Consistent improvement observed across the majority of sub-groups Source: Company data on file.
PHASE 3 TRIAL | Baseline characteristics balanced across treatment arms and reflect real world melanoma patients (1 of 2) Consistent improvement observed across the majority of sub-groups Source: Company data on file. Effect observed in both PD-L1+ and PD-L1- patients, with profound effect In PD-L1 negative group, with mPFS was 16.6 months in patients treated with Cylembio plus pembrolizumab compared to 3.0 months in patients treated with pembro alone, HR: 0.54 (CI 0.35-0.85) (nominal p=0.006)
PHASE 3 TRIAL | Baseline characteristics balanced across treatment arms and reflect real world melanoma patients (2 of 2) Consistent improvement observed across the majority of sub-groups Source: Company data on file.
PHASE 3 TRIAL | Baseline characteristics balanced across treatment arms and reflect real world melanoma patients (2 of 2) Consistent improvement observed across the majority of sub-groups Source: Company data on file. Per phase 1/2 trial population, excluding patients with prior anti-PD1 exposure** (n=36): mPFS was 24.8 months vs. 11.0 months HR: 0.74 (CI 0.56-0.98) (nominal p=0.037)
PHASE 3 TRIAL | Baseline characteristics balanced across treatment arms and reflect real world melanoma patients (2 of 2) Consistent improvement observed across the majority of sub-groups Source: Company data on file. Excluding acral/mucosal patient (n=24) per protocol**: Cylembio plus pembrolizumab 22.1 months vs. 11.1 months for control arm
PHASE 3 TRIAL | Trend in Overall Survival Benefiting Cylembio (not yet mature) separated early and widens Source: Company data on file.
SAFETY DATA | Treatment with Cylembio did not add significant systemic toxicity compared to patients treated with pembrolizumab monotherapy IO102-IO103 + Pembrolizumab (N=200) Pembrolizumab (N=198) Time at risk [months] [1] Mean 14.9 14.1 Patients with AEs, n (%) 194 (97.0) 187 (94.4) Patients with treatment-related AEs [2], n (%) 171 (85.5) 161 (81.3) Patients with SAEs, n (%) 64 (32.0) 64 (32.3) Patients with treatment-related SAEs [2], 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 investigator assessed immune-related AEs (irAE) not included in imAE definition, n (%) 102 (51.0) 99 (50.0) Patients with AEs of clinical interests (ECI), n (%) 2 (1.0) 0 Patients with AEs leading to infusion interruption in pembrolizumab, n (%) 2 (1.0) 1 (0.5) Patients with AEs leading to treatment withhold in IO102-IO103, n (%) 82 (41.0) 0 Patients with AEs leading to treatment withhold in pembrolizumab, n (%) 81 (40.5) 71 (35.9) Patients with AEs leading to discontinuation of study medication, n (%) 31 (15.5) 31 (15.7) Maximum CTCAE grade, n (%) Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 33 (16.5) 82 (41.0) 70 (35.0) 5 (2.5) 4 (2.0) 25 (12.6) 88 (44.4) 64 (32.3) 5 (2.5) 5 (2.5) Patients with injection site reactions 112 (56.0) 2 (1.0) Source: Company data on file. Per protocol, if pembrolizumab was withheld, IO102-IO103 would also be withheld
PHASE 3 TRIAL | Topline results Cylembio demonstrated PFS benefit regardless of prespecified subgroups or stratification factors Median progression free survival, ITT analysis: Cylembio plus pembrolizumab 19.4 months vs. 11.0 months for patients treated with pembrolizumab alone, HR=0.77 (CI 0.58-1.00) (p=0.056)* Overall Survival trend favoring Cylembio combination arm, OS not yet mature HR = 0.79 (CI 0.57, 1.10) Well-tolerated with no significant added systemic toxicity compared to pembrolizumab alone * Statistical significance threshold for this study was p=0.045. **Post-hoc analysis. Source: Data on file. In PD-L1 negative group, mPFS was 16.6 months in patients treated with Cylembio plus pembrolizumab compared to 3.0 months in patients treated with pembro alone, HR: 0.54 (CI 0.35-0.85) (nominal p=0.006) Per phase 1/2 trial population, excluding patients with prior anti-PD1 exposure** (n=36): mPFS was 24.8 months vs. 11.0 months HR: 0.74 (CI 0.56-0.98) (nominal p=0.037) (n=371)
1st Line Advanced Melanoma Treatment Landscape Omid Hamid, MD, Director, Clinical Research and Immunotherapy at The Angeles Clinic and Research Institute, A Cedars Sinai Affiliate
MARKET OPPORTUNITY IN ADVANCED MELANOMA | Cylembio® profile has potential to fulfill significant unmet needs and drive market leadership 1. https://gco.iarc.fr/today/en/; 2. https://seer.cancer.gov/statfacts/html/melan.html; 3. Melanoma Research Alliance; 4. Larkin et al. N Engl J Med 2019;381:1535-1546; 5. Robert et al. Lancet Oncol 2019;20:1239-1251; 6. Tawbi et al. N Engl J Med 2022;386:24-34; 7. Weber et al. Oncologist. 2016;21(10):1230-1240; 8. Evaluate Pharma 2025 Melanoma incidence is increasing1-3 ~331,000 patients newly diagnosed annually (global) ~58,000 patient deaths annually (global) 30% 5-year survival rate for patients in stage IV Cylembio® profile has potential to drive market leadership8 2030 2024 14 12 10 8 6 4 2 +9% 13.2 9.4 Forecast global Melanoma Drug Sales in USD billions US CAGR Patients and physicians seek more effective treatment options4-7 ~50% of patients progress within one year of treatment
COMPETITIVE LANDSCAPE | If approved, Cylembio would be well-positioned for the treatment of first line advanced melanoma Cylembio (IOB-013) Opdualag (RELA-047) Ipi/Nivo (CM-067) Pembro KN-006 Pembro n=204 Cylembio + pembro n=203 Nivo n=359 Nivo+Rela n=355 Ipi n=315 Ipi+Nivo n=314 Ipi n=181 Pembro n=368 PFS 11m 19.4m 4.6m 10.2m 6.9m 11.5m 4.1m 11.6m Comparisons across clinical trials should be interpreted with caution. No head-to-head studies were conducted and differences in study design, patient populations, endpoints, and other factors limit the ability to draw direct or reliable conclusions between separate trials. Any such comparisons presented here are for general informational purposes only. 1. https://www.sciencedirect.com/science/article/pii/S0959804925003296; 2. https://www.nejm.org/doi/full/10.1056/NEJMoa2407417; 3. https://www.annalsofoncology.org/action/showPdf?pii=S0923-7534%2824%2903910-3; 4. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30388-2/abstract); PFS, progression free survival.
Company Milestones
MILESTONES | Several important milestones expected through 2026 Cylembio | 1L Advanced Melanoma Top-line readout of primary endpoint in phase 3 study, 3Q25 Discussions with FDA, Fall 2025; potential BLA submission thereafter Initial data Complete enrollment in neoadj/adj Ph2 cohorts Final data from first-line Ph2 Initial data from neoadjuvant/adjuvant Ph2 Complete enrollment in neoadj/adj Ph2 cohort IND enabling studies H1 2025 H2 2025 Continue readiness for IND submission Cylembio | Neoadjuvant / adjuvant Melanoma Cylembio | 1L Lung (NSCLC) Cylembio | Head & Neck (SCCHN) IO112 | Solid Tumors (pre-clinical) IO170 | Solid Tumors (pre-clinical) Final data from Ph2 BLA, biologics license application; IND, investigational new drug; NSCLC, non-small cell lung cancer; SCCHN, squamous cell carcinoma of the head and neck Potential US approval Potential US launch Potential EU MAA submission 2026 IND submission Additional data Cash into 1Q2026 with 2Q cash balance of $28M* and second tranche of EIB loan received on July 4, 2025 * On May 6, 2025, the Company drew on the EIB tranche A loan facility and obtained funding in the principal amount of €10.0 million and on July 4, 2025, the Company drew the second tranche of the EIB loan facility and obtained €112.5 million, before payment of certain fees and transaction related expenses;
Breaking Boundaries. Igniting Change. IO Biotech Corporate Presentation Pivotal Phase 3 Trial Results Conference Call 11August2025