Tagworks Pharmaceuticals Announces CTA Authorization and Initiation of Phase 0/1 Clinical Trial for TGW211, a Radiopharmaceutical for the Treatment of HER2+ Tumors

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• USA - English

• TGW211 is a next-generation, first-in-class HER2-directed radioimmunoconjugate developed based on Tagworks' proprietary Click-to-Release – bioorthogonal, in vivo click chemistry – linker platform
• TGW211 is designed to achieve strong tumor uptake with selective and rapid elimination of undesired circulating radioactivity
• Phase 0/1 clinical trial (CleavHER trial) of TGW211 initiated, sponsored by the Radboud University Medical Center in the Netherlands; enrollment of first patients expected by end of 2025 and preliminary safety and dosimetry data expected in 2026

NIJMEGEN, Netherlands and BOSTON, Oct. 15, 2025 /PRNewswire/ -- Tagworks Pharmaceuticals BV ("Tagworks"), a clinical-stage precision oncology company using its proprietary Click-to-Release treatment platform to develop a new standard of care for patients suffering from solid tumors, today announced that the Dutch regulatory authorities approved the Clinical Trial Application (CTA) for the CleavHER Phase 0/1 clinical trial, sponsored by the Radboud University Medical Center (Radboudumc), evaluating TGW211, a first-in-class radioimmunoconjugate, in patients with HER2-positive tumors.

"The CTA approval and initiation of our second clinical trial this year mark a major milestone for Tagworks and validate the potential of our Click-to-Release platform," said Marc Robillard, PhD, Chief Scientific Officer and Co-Founder of Tagworks. "Unlike peptides, radiolabeled monoclonal antibodies avoid high radiation doses in the kidney. Many antibody therapies show strong tumor uptake, making them ideal vehicles for targeted radiotherapy. However, their clinical use has been limited by prolonged blood circulation resulting in myelotoxicity. Our Click-to-Release technology addresses this limitation by enabling precise tumor targeting and rapid clearance from healthy tissue—broadening the therapeutic window and unlocking new potential in radioimmunoconjugate development."

Under an investigator-initiated trial agreement, Tagworks and Radboudumc have initiated the first-in-human Phase 0/1 clinical development of TGW211 in a single center, open-label imaging study in patients with HER2-positive solid tumors. The primary objectives of the study are to determine safety and tolerability of Indium-111 (¹¹¹In)-labeled TGW211, and secondary endpoints include evaluating the pharmacokinetics and dosimetry of ¹¹¹In-TGW211 in tumor and healthy tissue. The study is currently recruiting and aims to enroll up to 18 patients.

"The Click-to-Release platform has the potential to redefine the therapeutic window of antibodies as vectors for radioactivity and represents a paradigm shift in the use of radiolabeled monoclonal antibodies in cancer treatment by enabling selective removal of circulating radioactivity after tumor targeting, enhancing the tumor-to-blood dose ratio and reducing healthy tissue exposure," said Prof. James Nagarajah, MD, Principal Investigator of the study at Radboudumc. "We are proud to lead the first clinical evaluation of TGW211 and help advance this innovative approach for patients."

Based on preclinical data recently highlighted at the European Association of Nuclear Medicine Congress, ¹¹¹In-TGW211 has shown positive results in in vitro functional assays and in vivo animal models. These results suggest that TGW211 may have a positive effect on reducing the unfavorable radiation burden in patients undergoing targeted therapy and improve imaging by reducing background noise.

Preliminary safety and dosimetry data from the Phase 0/1 clinical trial is expected in 2026 and may support continued development towards the application of a Phase 1 therapeutic study with Actinium-225 or Lutetium-177-labeled TGW211.

About TGW211
TGW211 is a radiopharmaceutical targeting Human Epidermal Growth Factor Receptor 2 (HER2), a well-validated target in multiple solid tumors. TGW211 is a HER2-directed antibody (trastuzumab) radioimmunoconjugate linked using Tagworks' proprietary Click-to-Release linker platform. TGW211 is administered intravenous (IV) first and allowed to bind to HER2 and internalize in the tumor. Then a non-cell permeable, small molecule trigger is administered IV, resulting in selective chemical cleavage of the linker of the remaining systemically circulating TGW211, release and rapid elimination of the radionuclide from the body through the kidneys. ¹¹¹In-TGW211 is under evaluation in an open-label, Phase 0/1 clinical trial (CleavHER trial) designed to evaluate safety, pharmacokinetics and dosimetry in patients with HER2-positive solid tumors.

About Tagworks Pharmaceuticals
Tagworks Pharmaceuticals is a clinical-stage precision oncology company using its proprietary Click-to-Release linker platform to develop a new standard of care for patients suffering from solid tumors. Tagworks is developing a pipeline of novel cancer treatments leveraging its proprietary Click-to-Release technology in a range of therapeutics modalities, including antibody-drug conjugates (ADCs) and targeted radiopharmaceutical therapies. Its lead programs include, TGW101, an ADC targeting TAG-72, a non-internalizing marker found on the surface of many solid tumor cells and TGW211, a radioimmunoconjugate targeting HER2-positive cancers. The Company is headquartered in the Netherlands with operations in the U.S. For more information, visit us at www.tagworkspharma.com.

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