Tagworks Pharmaceuticals has announced the initiation of the third dosing level in its ongoing Phase 1 clinical trial for TGW101, a next-generation antibody-drug conjugate (ADC) designed to treat solid tumors. The advancement represents a significant milestone for the first-in-class therapeutic that targets TAG-72, a tumor-associated glycoprotein, using the company's proprietary Click-to-Release linker chemistry.
Novel Click Chemistry Approach
TGW101 distinguishes itself as the first bioorthogonal, in vivo click chemistry-activated ADC, incorporating a monomethyl auristatin E (MMAE) payload. This innovative approach enables superior control of tumor payload activity compared to conventional ADC therapies. The drug targets TAG-72, a non-internalizing marker found on the surface of many solid tumor cells, through a unique two-step administration process.
The therapeutic mechanism involves first administering TGW101 intravenously, allowing it to bind to TAG-72 in the tumor. Subsequently, a small molecule trigger is administered intravenously, resulting in selective chemical cleavage of the linker of the tumor-bound TGW101. This process releases MMAE in the extracellular tumor microenvironment, enabling diffusion into surrounding tumor cells while minimizing impact on healthy tissue.
Phase 1 Trial Progress
The ongoing Phase 1 trial is a multicenter, open-label, dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of TGW101 in patients with relapsed or refractory solid tumors. The primary objectives include determining the maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and optimal dose regimen for cohort expansion.
"We are pleased to report continued progress in our Phase 1 clinical trial of TGW101 which reflects our strong operational execution and commitment to advancing our pioneering Click-to-Release technology," said Ken Mills, Chief Executive Officer of Tagworks. "The Safety Oversight Committee's decision to proceed to the third dose level highlights TGW101's favorable safety profile to date."
The trial has successfully initiated three dose levels following favorable safety reviews by the Safety Oversight Committee (SOC). Up to seven dose levels are currently planned, with the maximum dose potentially updated based on evolving clinical safety and pharmacokinetic data. The study aims to enroll up to 50 patients across sites in the United States, with potential expansion to additional regions.
Clinical Expectations and Timeline
Mills expressed optimism about TGW101's potential to address significant unmet needs in treating advanced solid tumors while overcoming limitations observed with other ADC therapies. The company expects to share preliminary data from the study, including safety, pharmacokinetics, and potential early signs of clinical activity, in early to mid-2026.
The advancement to the third dose level demonstrates the therapeutic's promising safety profile and represents continued progress in Tagworks' mission to develop a new standard of care for patients suffering from solid tumors. The company's Click-to-Release treatment platform targets clinically validated tumor markers that have remained out of reach of current therapies.
Company Background
Tagworks Pharmaceuticals is a clinical-stage precision oncology company headquartered in the Netherlands with operations in the United States. Beyond TGW101, the company is developing a pipeline of novel cancer treatments leveraging its Click-to-Release technology across various therapeutic modalities, including ADCs and targeted radiopharmaceutical therapies.
