Preclinical posters from IO Biotech’s pipeline reported tumor growth inhibition and, in a lung metastasis model, reduced metastatic burden. IO112, a peptide vaccine targeting arginase 1, expanded Arg1-specific T cells and appeared to reprogram immunosuppressive myeloid populations, including tumor-associated macrophages, toward a pro-inflammatory phenotype. IO170, a TGF-β–directed vaccine, induced T-cell responses against TGF-β–expressing cells with associated anti-tumor activity in vivo.
The company unveiled the data at SITC 2025 and flagged an IND filing for IO112 in 2026, positioning it as the following program to enter the clinic after its lead vaccine, Cylembio. The two assets extend IO Biotech’s T-win platform beyond tumor antigen targeting into direct modulation of suppressive elements of the tumor microenvironment. In this space, prior small-molecule arginase inhibitors and systemic TGF-β blockers have struggled to deliver consistent clinical benefit.
Strategically, this is an expansion play aimed at differentiating in a crowded immuno-oncology space by shifting the mechanism from enzymatic blockade to immune-mediated cell targeting. By vaccinating to generate T cells against Arg1-expressing myeloid cells and TGF-β–expressing stromal or immune components, IO Biotech is betting that precision immunomodulation can avoid the efficacy–toxicity tradeoffs that have dogged pathway-level inhibition. It also gives the company optionality across solid tumors where Arg1-positive myeloid cells and TGF-β signaling are prevalent, potentially enabling tumor-agnostic early trials with biomarker-enriched cohorts rather than single-indication bets.
For clinical operations, the read-through is clear: if INDs proceed on schedule, first-in-human studies will be biomarker-heavy and logistics-driven. Expect protocols built around serial biopsies, high-frequency PBMC sampling, and centralized immunomonitoring to capture on-mechanism signals, including TAM polarization, MDSC depletion, Arg1 activity, and TGF-β pathway readouts. Sites with tissue-acquisition capacity and immune-assay infrastructure will be at an advantage. As off-the-shelf peptides, these vaccines could be simpler to operationalize than cell therapies, but adjuvant selection, dosing cadence, and combination backbones will dictate visit intensity and AE surveillance. Safety oversight will be a gating factor: TGF-β modulation raises familiar concerns about tissue homeostasis and inflammation, and myeloid-targeted responses can carry risks of cytokine release and autoimmunity, necessitating tight protocol guidance, rapid AE adjudication, and clear stopping rules.
For sponsors and CROs, the platform pushes toward adaptive designs that integrate pharmacodynamic endpoints early, with contingency to pivot between monotherapy and PD-1 combinations if objective response rates lag. Given the failures of prior TGF-β and arginase agents, regulators will expect robust translational packages that link TME remodeling to clinical activity and avoid broad systemic blockade. CMC will matter: consistent peptide manufacturing, potency assays aligned with T-cell activation, and cold-chain reliability must be locked down before expansion cohorts.
The following milestones to watch are the IO112 IND specifics and the initial clinical protocol choices: tumor selection, biomarker inclusion criteria, adjuvant and dosing strategy, and whether the company starts with combination therapy to amplify signal detection. Early human data will need to show not only safety and immunogenicity but credible evidence of TME reprogramming in matched biopsies. The central risk is translational fidelity; many TME-targeting approaches have performed well preclinically but underdelivered in heterogeneous human tumors. If IO Biotech can demonstrate on-target remodeling with manageable safety and even modest response signals in checkpoint-refractory settings, it could reopen clinical interest in TME-directed vaccination and set a template for operationally tractable, biomarker-led trials in this category.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
