Tizona Therapeutics Presents Clinical Translational Evidence of Dual Innate and Adaptive Immune Activation with TTX-080, a First-in-Class HLA-G Antagonist, in Patients with Advanced Solid Tumors at SITC 2025

Enrolling patients in ongoing randomized Phase 1b trial in MSS metastatic colorectal cancer, evaluating TTX-080 in combination with cetuximab + FOLFIRI

SOUTH SAN FRANCISCO, Calif., Nov. 07, 2025 (GLOBE NEWSWIRE) — Tizona Therapeutics, Inc., a clinical-stage biotechnology company developing next-generation immunotherapies designed to overcome tumor immune evasion, today announced the presentation of new clinical translational data on its lead program TTX-080, a first-in-class, fully human monoclonal antibody targeting HLA-G, at the 40th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) being held November 5-9, 2025, in National Harbor, Maryland.

The poster, titled “TTX-080, A First-in-Class HLA-G Specific Antagonist, Increases Distinct Innate and Adaptive Immune Cells in the Tumor Microenvironment and Periphery” (Abstract #570), presents analyses from Tizona’s single-arm Phase 1 trial of TTX-080 as monotherapy and in combination with cetuximab or pembrolizumab in patients with advanced solid tumors.

“These translational data provide compelling evidence in humans that HLA-G blockade can activate both innate and adaptive immunity, which is differentiated from the traditional PD-1, PD-L1, and CTLA-4 checkpoints,” said Courtney Beers, Ph.D., Chief Scientific Officer of Tizona Therapeutics. “Together, these data support the potential of this first-in-class antibody to extend benefit to patients whose tumors are unresponsive to existing treatment options. We look forward to further advancing this program through the ongoing randomized Phase 1b investigation of TTX-080 in combination with cetuximab/FOLFIRI in metastatic MSS colorectal cancer.”

Key Clinical Translational Findings
Patient tumor biopsies, blood samples, and pharmacokinetic data were analyzed and demonstrated that TTX-080:

• Activates innate and adaptive immune pathways, including increased antigen-experienced CD8⁺ T cells, activated CD4⁺ T cells, and Ki67⁺ NK cells.
• Induces immune-regulating chemokines CXCL9 and CXCL10.
• Enhances myeloid and effector T-cell gene signatures in the tumor microenvironment.
• Demonstrates biological activity even in low-TMB (≤ 20 mut/Mb) tumors, which are historically less responsive to T-cell-focused checkpoint inhibitors.
• Exhibits well-behaved pharmacokinetics, supporting a biologically active dose of 20 mg/kg Q3W, with low immunogenicity and minimal target-mediated drug disposition.

Tizona Therapeutics is currently enrolling first or second line patients with microsatellite stable (MSS) RAS/RAF wild-type metastatic colorectal cancer in an ongoing randomized Phase 1b study, evaluating TTX-080 + cetuximab + FOLFIRI versus cetuximab + FOLFIRI alone (NCT04485013).

HLA-G is a non-classical MHC class I molecule expressed on many solid tumors that drives immune suppression through the ILT2 and ILT4 receptors. By blocking these interactions, TTX-080 seeks to reverse immune tolerance and promote anti-tumor activity in ways distinct from currently available immunotherapies.

About Tizona Therapeutics
Tizona Therapeutics, Inc. is a clinical-stage biotechnology company developing next-generation immunotherapies that modulate the immune system to overcome tumor resistance. The company’s lead program, TTX-080, is a first-in-class, fully human monoclonal antibody that specifically binds HLA-G to block its interactions with ILT2 and ILT4 receptors on immune cells. TTX-080 is being studied in an ongoing randomized Phase 1b trial in MSS metastatic colorectal cancer, evaluating TTX-080 + cetuximab + FOLFIRI versus cetuximab + FOLFIRI alone. Tizona is headquartered in South San Francisco, California. Follow us on LinkedIn.

Media Contact
Lori Murray
lori.murray@captivate-comms.com