On September 29, 2025 IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines, reported 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) (Press release, IO Biotech, SEP 29, 2025, View Source [SID1234656318]). 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.
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"We had a productive meeting with the FDA; while this is not the outcome we had hoped for, we respect the 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 the 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 $1.0 – $1.5 million in the third quarter of 2025 related to the restructuring, which includes an approximate 50 percent reduction in full-time employees.
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.