TTX-080 / Tizona Therap - LARVOL DELTA

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 (GlobeNewswire) - "The poster...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....Key Clinical Translational Findings:...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."

P1 data • Solid Tumor

TTX-080, A First-In-Class HLA-G Specific Antagonist, Increases Distinct Innate and Adaptive Immune Cells in the Tumor Microenvironment and Periphery (SITC 2025) - "TTX-080 is currently in Phase 1 clinical development as a monotherapy and in combination with pembrolizumab, cetuximab (anti-EGFR IgG1:FcgR ADCC & ADCP competent), and FOLFIRI + cetuximab in patients with metastatic or advanced cancer.Here we present translational data demonstrating the significant TTX-080 on-mechanism activation of innate and adaptive immune cells in the tumor microenvironment and in the periphery validating the functional impact of HLA-G blockade on immune cells in a clinical setting.As a monotherapy, increased activation of myeloid genes (phagocytosis & ADCP) was observed comparing tumor samples pre- vs post-treatment...In addition, increased numbers of activated antigen experienced ILT2+CD8+ T cells (TEMRA), and CD4+ T cells were found highlighting changes to the adaptive immune response and differentiation of the HLA-G/ILT2/ILT4 pathway from conventional checkpoint therapies like anti-PD-(L)1, where exhausted T cells are predominately..."

Biomarker • Immune cell • IO biomarker • Tumor microenvironment • Tumor mutational burden • Oncology • Solid Tumor • CD4 • CD8 • CXCL10 • CXCL9 • FCGR2A • TMB

TTX-080-001: TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers (clinicaltrials.gov) - P1 | N=240 | Recruiting | Sponsor: Tizona Therapeutics, Inc | Active, not recruiting ➔ Recruiting | Trial primary completion date: Jun 2024 ➔ Jun 2027

Combination therapy • Enrollment open • Metastases • Monotherapy • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF

TTX-080-001: TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers (clinicaltrials.gov) - P1 | N=240 | Active, not recruiting | Sponsor: Tizona Therapeutics, Inc | Trial completion date: Jun 2024 ➔ Jun 2027 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • BRAF

Tizona Therapeutics Announces Expansion of Phase 1b Clinical Trial to Evaluate TTX-080 in Combination with EGFR Inhibitor Cetuximab and Chemotherapy in Advanced Colorectal Cancer (GlobeNewswire) - "Tizona Therapeutics, Inc...today announced the initiation of two randomized arms within the ongoing Phase 1b clinical trial of TTX-080, a novel, first-in-class antibody targeting HLA-G. Patients with biomarker-defined metastatic colorectal cancer (mCRC) will be enrolled to receive either TTX-080 plus cetuximab and FOLFIRI or cetuximab and FOLFIRI alone in the second-line setting."

Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology

Results from phase 1a/1b analyses of TTX-080, a first in class HLA-G antagonist, in combination with cetuximab in patients (pts) with metastatic colorectal cancer and head and neck squamous cell carcinoma. (ASCO 2024) - P1 | "This Ph1a/1b study evaluated the safety and preliminary efficacy of TTX-080 alone or in combination with cetuximab (Cetx) or pembrolizumab (Pem) in multiple solid tumor cohorts (NCT04485013). TTX-080 is well tolerated alone and in combination with Cetx. TTX-080 + Cetx demonstrates promising activity in pts with HPV-Neg HNSCC and WT RAS/BRAF/Her2-Neg mCRC as manifested by the responses and PFS. These early findings warrant further investigation of TTX-080 + Cetx in a randomized controlled study against standard of care in mCRC and HNSCC."

Clinical • Combination therapy • Metastases • P1 data • Anemia • Colorectal Cancer • Fatigue • Gastrointestinal Cancer • Head and Neck Cancer • Hematological Disorders • Musculoskeletal Pain • Oncology • Pain • Pruritus • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • BRAF • HER-2

Tizona Therapeutics Presents Phase 1b TTX-080 Clinical Data in Advanced Colorectal Cancer and Head and Neck Squamous Cell Carcinoma at ASCO 2024 (GlobeNewswire) - P1a/1b | N=240 | NCT04485013 | Sponsor: Tizona Therapeutics, Inc | "Tizona Therapeutics, Inc...announced first-in-human Phase 1b clinical data of TTX-080...The most common Grade 3 adverse events (AEs) in patients with mCRC were increases in AST (n=3) and ALT (n=3), fatigue (n=1), dermatitis acneiform (n=1) and myalgias (n=1)...TTX-080 plus cetuximab demonstrated anti-tumor activity in patients with WT RAS, BRAF, HER2-negative mCRC...Median progression-free survival (PFS) was 24.4 weeks, with a 36-week PFS rate of 47%; The most common Grade 2 AEs were anemia (n=2), fatigue (n=1) and an increase in AST (n=1). One (1) patient experienced Grade 4 anemia...TTX-080 in combination with cetuximab generated anti-tumor activity in patients with human papillomavirus (HPV)-negative mHNSCC...Median PFS was 23.9 weeks, with a 24-week PFS rate of 43%."

P1 data • Colorectal Cancer • Squamous Cell Carcinoma of Head and Neck

TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers (clinicaltrials.gov) - P1 | N=240 | Active, not recruiting | Sponsor: Tizona Therapeutics, Inc | Phase classification: P1a/1b ➔ P1

Combination therapy • Metastases • Monotherapy • Phase classification • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers (clinicaltrials.gov) - P1a/1b | N=240 | Active, not recruiting | Sponsor: Tizona Therapeutics, Inc | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2023 ➔ Dec 2023

Combination therapy • Enrollment closed • Metastases • Monotherapy • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers (clinicaltrials.gov) - P1a/1b | N=240 | Recruiting | Sponsor: Tizona Therapeutics, Inc | Trial primary completion date: Dec 2022 ➔ Jun 2023

Combination therapy • Monotherapy • Trial primary completion date • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

Tizona Initiates Phase 1b Expansion Study of TTX-080 in Advanced Refractory or Resistant Malignancies (Businesswire) - "Tizona Therapeutics, Inc...announced....that its lead investigational therapy, TTX-080, a novel antibody targeting HLA-G, has advanced to Phase 1b. This phase includes expansion tumor arms to evaluate the safety and efficacy of TTX-080 as monotherapy and combination regimens in patients with advanced malignancies.....The Phase 1b is a dose expansion study designed to assess TTX-080 as monotherapy and in combination with either pembrolizumab or cetuximab in patients with advanced refractory or resistant solid tumor malignancies, including head and neck squamous cell carcinoma, non-small cell lung cancer, colorectal cancer, and triple negative breast cancer."

Trial status • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers (clinicaltrials.gov) - P1a/1b; N=200; Recruiting; Sponsor: Tizona Therapeutics, Inc; Phase classification: P1 ➔ P1a/1b; N=40 ➔ 200; Trial completion date: Feb 2022 ➔ Jun 2024; Trial primary completion date: Aug 2021 ➔ Dec 2022

Clinical • Combination therapy • Enrollment change • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer

[VIRTUAL] Targeting HLA-G-mediated immunosuppression with a first-in-class antagonist antibody (SITC 2020) - "Conclusions TTX-080 reverses HLA-G-mediated suppression of ILT2+ and ILT4+ immune cells that are found within the tumor microenvironment. Blockade of HLA-G using TTX-080 therefore has the potential to reverse broad immune suppression in patients with advanced solid tumors by reinvigorating CD8+ T cells, enhancing NK cytolytic activity, and increasing macrophage phagocytosis."

Oncology • Solid Tumor • CD8

[VIRTUAL] Targeting HLA-G-mediated immunosuppression with a first-in-class antagonist antibody (SITC 2020) - "Conclusions TTX-080 reverses HLA-G-mediated suppression of ILT2+ and ILT4+ immune cells that are found within the tumor microenvironment. Blockade of HLA-G using TTX-080 therefore has the potential to reverse broad immune suppression in patients with advanced solid tumors by reinvigorating CD8+ T cells, enhancing NK cytolytic activity, and increasing macrophage phagocytosis."

Oncology • Solid Tumor • CD8

Gilead Buys into Tizona's Anti-HLA-G Strategy. (PubMed, Cancer Discov) - "Gilead announced plans in July to pay $300 million for a 49.9% stake in Tizona Therapeutics, with the option to buy the rest of the company for $1.25 billion. Whether Gilead follows through with the acquisition will hinge on how well Tizona's investigational HLA-G inhibitor, TTX-080, fares in early-stage clinical trials."

Journal

Gilead Sciences Secures Exclusive Option to Acquire Tizona Therapeutics for $300 Million (Businesswire) - "Gilead Sciences, Inc...announced that it will invest $300 million to acquire a 49.9 percent equity interest in Tizona Therapeutics, Inc...Gilead will also receive an exclusive option to acquire the remainder of Tizona for up to an additional $1.25 billion, including an option exercise fee and potential future milestone payments...The U.S. Food and Drug Administration has cleared Tizona’s Investigational New Drug (IND) application for TTX-080, and in the third quarter of this year, Tizona plans to initiate a Phase 1 clinical trial evaluating TTX-080 both as a monotherapy and in combination with other agents in patients with advanced cancers....Tizona will spin off TTX-030, the company’s investigational, first-in-class anti-CD39 antibody partnered with AbbVie, into a separate entity prior to closing of this transaction. TTX-030 is not subject to this agreement."

IND • M&A • New P1 trial • Oncology • Solid Tumor

TTX-080 HLA-G Antagonist in Subjects With Advanced Cancers (clinicaltrials.gov) - P1; N=40; Recruiting; Sponsor: Tizona Therapeutics, Inc

Clinical • New P1 trial • Oncology • Solid Tumor

Tizona Initiates Clinical Development of TTX-080 in Advanced Cancers (GlobeNewswire) - "Tizona Therapeutics, Inc…announced today that its Investigational New Drug (IND) application for TTX-080, a novel antibody targeting HLA-G, has been cleared by the U.S. Food and Drug Administration (FDA). The first clinical study of TTX-080 will be initiated in advanced cancers in Q3 2020…Tizona plans to evaluate TTX-080 as both a monotherapy and in combination therapy in advanced cancers in a Phase 1 clinical trial."

IND • New P1 trial • Oncology