IO Biotech Provides Update Following Pre-BLA Meeting with FDA
IO Biotech (NASDAQ:IOBT) received a setback as the FDA recommended against submitting a Biologics License Application (BLA) for Cylembio based on the IOB-013 clinical trial data. The trial, which evaluated Cylembio plus pembrolizumab, showed improved progression-free survival (PFS) but narrowly missed statistical significance.
The company plans to design a new registrational study and will continue discussions with FDA and European regulators. In response, IO Biotech is implementing a restructuring plan, including a 50% workforce reduction. The company expects to incur a $1.0-$1.5 million restructuring charge in Q3 2025 and has capital to operate into Q1 2026.
- Company has sufficient capital to operate into Q1 2026
- Treatment showed improved progression-free survival despite missing statistical significance
- Potential pathway remains open with European regulators
- FDA recommended against BLA submission based on current trial data
- Clinical trial narrowly missed statistical significance
- 50% workforce reduction implemented
- Expected restructuring charge of $1.0-$1.5 million in Q3 2025
- New registrational study required, potentially delaying approval
Insights
FDA rejection of IO Biotech's BLA submission path creates significant regulatory setback, forcing 50% staff reduction and new trial design.
The FDA's recommendation against submitting a BLA for Cylembio represents a significant regulatory setback for IO Biotech. The company's IOB-013 trial results for its cancer vaccine narrowly missed statistical significance for progression-free survival when combined with pembrolizumab. This regulatory roadblock effectively resets the timeline for potential approval, as the company must now design and conduct an entirely new registrational trial.
This outcome substantially delays the commercialization pathway for Cylembio in the US market. The company's plan to engage with European regulators suggests a potential strategy to pursue approval in the EU with the existing data, though this remains uncertain. The regulatory divergence between regions is not uncommon, especially for therapies with borderline statistical results.
The workforce reduction of approximately 50 percent indicates the severity of this setback, as the company attempts to extend its cash runway while navigating this challenging period. With capital projected to last only until
The FDA's recommendation against IO Biotech's BLA submission for Cylembio creates a substantial commercial delay in the competitive melanoma market. First-line advanced melanoma represents a significant commercial opportunity, with pembrolizumab (Keytruda) already established as standard of care. Cylembio was positioned as a potential combination therapy to enhance pembrolizumab's efficacy.
The narrow miss on statistical significance in the IOB-013 trial—specifically on the progression-free survival (PFS) endpoint—highlights the challenges in demonstrating sufficient incremental benefit in the current melanoma treatment landscape. While the company maintains confidence in Cylembio's therapeutic potential, the requirement for an entirely new registrational study will likely add 2-3 years minimum to the approval timeline.
The
The company's parallel strategy to pursue European approval suggests they believe the existing data may meet the EMA's standards, potentially providing an earlier revenue stream. However, the melanoma therapeutic landscape continues to evolve rapidly with numerous competing modalities, including other immunotherapies, targeted therapies, and cell therapies advancing through clinical development, further complicating Cylembio's market potential by the time of a potential approval.
- FDA recommends that IO Biotech not submit a Biologics License Application (BLA) based on the data from the IOB-013 clinical trial
- Company plans to design new registrational study for Cylembio for the treatment of first-line patients with advanced melanoma
- Company implementing a restructuring, reducing its workforce by approximately 50 percent
NEW YORK, Sept. 29, 2025 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines, today provided an update on the regulatory pathway for Cylembio® (imsapepimut and etimupepimut, adjuvanted) following a pre-BLA meeting with the U.S. Food and Drug Administration (FDA). The FDA has recommended that IO Biotech not submit a BLA based on the data from the IOB-013 clinical trial. As previously announced, in the IOB-013 trial, treatment with Cylembio plus pembrolizumab improved progression free survival (PFS), however the results narrowly missed statistical significance. The company plans to continue the dialogue with FDA to align on the design of a potential new registrational study for Cylembio.
“We had a productive meeting with FDA; while this is not the outcome we had hoped for, we respect FDA’s feedback and remain confident in the therapeutic potential of Cylembio,” said Mai-Britt Zocca, PhD, president and chief executive officer of IO Biotech. “We look forward to continuing the dialogue with FDA to align on the design for a potential new registrational study. Additionally, we plan to discuss the data from our IOB-013 study with European regulators and determine a path to submission in the EU.”
The company is implementing a plan to conserve capital while it pursues a pathway to regulatory approval for Cylembio and works to complete ongoing studies. The company currently has capital to run its operations into the first quarter of 2026 and is restructuring to reduce the company’s ongoing expense structure. The company expects to incur a non-recurring charge of between
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 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 the IOB-013/KN-D18 Phase 3 Clinical Trial
IOB-013/KN-D18 (ClinicalTrials.gov: NCT05155254) is 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 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.
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 regulatory pathway for Cylembio/IO102-IO103, the timing or outcome of communications with regulatory authorities including the FDA and EMA, the timing or outcome of the submission of marketing applications, including a BLA, for Cylembio, the timing or outcome of the launch of Cylembio, and statements regarding other current or future clinical trials, their timing, 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.
Contact:
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
FAQ
What did the FDA recommend to IO Biotech (IOBT) regarding Cylembio's BLA submission?
How many employees will be affected by IO Biotech's 2025 restructuring?
What was the outcome of IO Biotech's IOB-013 trial for Cylembio?
How long can IO Biotech operate with its current capital?
What is the expected restructuring charge for IO Biotech in Q3 2025?
