Nivolumab

Findings provide scientific insights into the contributions of IDO1 and PD-L1 vaccination to PD-1 blockade for the treatment of metastatic melanoma Five-year analysis of median progression free survival was 25.5 months These results reinforce the potential of immune-modulatory vaccination NEW YORK, Dec. 15, 2025 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, immune-modulatory, off-the-shelf therapeutic cancer vaccines, today announced the publication in Nature Communications of the long-term clinical and immunological outcomes from MM1636, the Phase 1/2 trial evaluating the investigational peptide vaccine IO102-IO103 targeting both tumor cells and immune-suppressive cells expressing IDO1 and/or PD-L1, in combination with PD-1 blockade in the treatment of first line metastatic melanoma. The results of this trial supported a Breakthrough Therapy Designation for the treatment of unresectable/metastatic melanoma in combination with pembrolizumab by the US Food and Drug Administration (FDA) and, together with the available preclinical and translational data, served as the foundation for IO Biotech’s decision to initiate the Phase 3 clinical trial in first-line advanced melanoma (IOB-013/KN-D18). The MM1636 results published today showed the five-year follow-up analysis of IO102-IO103 in combination with nivolumab in patients with metastatic melanoma, demonstrating durable clinical activity with a 25.5-month median progression-free survival (PFS). The results also showed the identification of potential vaccine-specific immune biomarkers of long-term benefit, not observed in a matched anti-PD-1 monotherapy cohort, suggesting a distinct vaccine-induced immune modulation increasing anti-tumor activity. These overall results provide a compelling rationale for integrating immune-modulatory vaccination into immunotherapy regimens for patients with melanoma. “These are very exciting data that continue reinforcing the scientific foundation of our immune-modulatory therapeutic approach and strengthens our belief in its potential to transform patient care,” said Mads Hald Andersen, DMSc, PhD, Director of the Center for Cancer Immune Therapy (CCIT) and scientific co-founder of IO Biotech. “IDO1 and PD-L1 are immune suppressive targets expressed in many cancers hence, we believe that IO102-IO103 could have pan-tumor activity. I am proud to be part of the team that is further developing this potential new treatment option.” “We are very encouraged that the long-term follow up data confirm the earlier results reported from this study. The notable median duration of response of more than 53 months and an impressive median overall survival of 60 months support the potential of IO102-IO103 as a first-line therapy for melanoma as part of a combination regimen.” said Inge Marie Svane, MD, PhD, Professor, Director of the National Center for Cancer Immune Therapy (CCIT) at the Copenhagen University Hospital, Herlev, clinical co-founder of IO Biotech and Principal Investigator in the IOB-013 Phase 3 Trial. “There continues to be a significant unmet need for innovative therapies that improve outcomes for cancer patients,” said Mai-Britt Zocca, PhD, President and CEO of IO Biotech. “These data strengthen our belief in Cylembio and in our approach to develop off-the-shelf, immune modulatory therapeutics, with pan-cancer potential.“ The article, titled “Five-year clinical outcome and immune biomarkers of durable response from the MM1636 trial on IDO/PD-L1 vaccination and PD-1 blockade in first line metastatic melanoma”, is now available online at https://www-nature-com.sutd.idm.oclc.org/articles/s41467-025-67508-8. 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® (IO102-IO103), 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). About the MM1636 Clinical Trial The MM1636 trial (ClinicalTrials.gov: NCT03047928), an investigator-initiated trial at the Copenhagen University Hospital, Herlev, enrolled 30 patients with metastatic melanoma. In this Phase 1/2 clinical trial, patients received the multi-antigen immunotherapeutic, IO102-IO103, in combination with the anti-programmed death 1 (PD-1) antibody nivolumab as first line treatment. Patients were treated with nivolumab according to the approved label for melanoma (3mg/kg bi-weekly for up to two years). IO102-IO103 was given from the start of administration of nivolumab and every second week for the first six weeks and thereafter, every fourth week for 41 weeks. The trial objectives were to assess safety, immune response in blood and biopsies as well as efficacy. 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® (IO102-IO103) 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. 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 regulatory authorities including the FDA, the timing or outcome of the submission of regulatory applications, including an IND for IO112, 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 and media:Maryann Cimino, Director of Investor Relations & Corporate CommunicationsIO Biotech, Inc.617-710-7305mci@iobiotech.com

Arcus Biosciences said it would discontinue the Phase III STAR-221 trial after an interim analysis found no survival advantage for its experimental domvanalimab-based regimen in first-line patients with upper gastrointestinal (GI) tract cancers.The news, which marks the latest in a string of high-profile disappointments for the TIGIT class, sent Arcus shares sliding over 14% on Friday.Despite TIGIT setbacks from the likes of Roche, Merck & Co., GSK and BeOne Medicines over the last few years, Arcus and partner Gilead Science pressed ahead with their approach.In October, they shared encouraging overall survival (OS) data from the Phase II EDGE-Gastric study of domvanalimab plus the anti-PD-1 antibody zimberelimab and chemotherapy as first-line treatment in 41 patients with locally advanced unresectable or metastatic gastric cancer. The triplet was associated with median OS of 26.7 months in both the overall population and a subset of 29 patients with PD-L1 tumour area positivity of at least 1% (see – Spotlight On: Arcus, Gilead’s gastric cancer readout is tentative step toward TIGIT resurrection).Low expectationsSTAR-221 was testing the same combination against standard-of-care with Bristol Myers Squibb's Opdivo (nivolumab) plus chemotherapy in 1040 patients who have locally advanced unresectable or metastatic gastric, gastroesophageal junction and oesophageal adenocarcinoma."Patients in the domvanalimab-containing arm derived the same benefit as patients treated in the control arm, and there were no new safety concerns," said Richard Markus, chief medical officer at Arcus, in a release Friday. The decision to drop the study followed a recommendation from the study's independent data monitoring committee citing futility. EDGE-Gastric will also be discontinued.However, the broader struggles with anti-TIGIT drugs had already led analysts to dial back their expectations, which were "very low" around domvanalimab's potential, according Wedbush's Robert Driscoll.R&D pivotArcus said it now plans to pivot its R&D efforts toward casdatifan, an oral HIF-2a inhibitor in development for clear cell renal cell carcinoma (ccRCC), as well as five small-molecule programmes targeting MRGPRX2, TNF, CCR6, CD89 and CD40L for inflammatory and autoimmune (I&I) diseases.At this year's American Society of Clinical Oncology (ASCO) meeting, Arcus unveiled the first combination data from the Phase I/Ib ARC-20 study, showing a 46% confirmed response rate for casdatifan plus Exelixis' Cabometyx (cabozantinib) in immunotherapy-experienced ccRCC, outperforming historical benchmarks for either agent alone.Arcus also plans to advance two oral I&I candidates into the clinic, with an MRGPRX2 inhibitor for atopic dermatitis and chronic spontaneous urticaria slated for 2026, followed by a TNF inhibitor for rheumatoid arthritis, psoriasis and inflammatory bowel disease in late 2026 to early 2027.CEO Terry Rosen said, "We are fortunate to be well capitalised and plan to focus our resources on casdatifan, including studying new early-line combinations in kidney cancer, broadening its development into new tumour types, and extending our capabilities beyond oncology." The company said it has about $1 billion in cash and investments to see it through to at least the second half of 2028.