Tagworks Pharmaceuticals Announces FDA Clearance of IND Application and Initiation of Phase 1 Clinical Trial for TGW101 and Appoints Keith Orford, MD, PhD, as Chief Medical Officer

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• TGW101 is a next-generation, first-in-class ADC targeting TAG-72 with an MMAE payload, developed based on Tagworks proprietary Click-to-Release linker chemistry; TGW101 is the first bioorthogonal, in vivo click chemistry-activated ADC, which enables superior control of tumor payload activity
• Phase 1 clinical trial of TGW101 initiated; Company plans to enroll up to 50 patients with advanced solid tumors in the U.S.
• Keith Orford, MD, PhD, brings over three decades of leadership in oncology research and clinical drug development and will oversee an emerging clinical pipeline of novel cancer treatments leveraging Click-to-Release technology, including ADCs and targeted radiopharmaceuticals

NIJMEGEN, Netherlands and BOSTON, April 22, 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 the U.S. Food and Drug Administration (FDA) cleared the investigational new drug (IND) application for a Phase 1 clinical trial evaluating TGW101, a first-in-class antibody drug-conjugate (ADC) targeting tumor associated glycoprotein 72 (TAG-72) with an monomethyl auristatin E (MMAE) payload, in patients with advanced solid tumors. The Company also announced the appointment of Keith Orford, MD, PhD, as Chief Medical Officer (CMO).

Tagworks initiated first-in-human Phase 1 clinical development of TGW101 in a multicenter, open-label, dose-escalation trial in patients with advanced solid tumors. The primary objectives of the study are to evaluate the safety and tolerability of TGW101 and identify the maximum tolerated dose, recommended dose, and regiment for cohort expansion. The study is currently recruiting in the U.S. and plans to enroll up to 50 patients.

"TAG-72 is a validated target with overexpression in many high unmet need solid tumors. However, due to its non-internalizing nature, this target has remained unreachable by current ADCs and other therapies which require uptake by tumor cells to activate their anti-tumor activity. TGW101's highly differentiated profile enables controlled MMAE payload release and activation in the tumor microenvironment without internalization by tumor cells. This controlled drug release is achieved through a click reaction of the ADC linker with a trigger molecule, which is administered in a second step," said Marc Robillard, Chief Scientific Officer and Co-Founder of Tagworks. "TGW101 has demonstrated a favorable safety profile as well as effective and durable responses in preclinical solid tumor models. The IND clearance and initiation of our Phase 1 clinical trial is a significant milestone for our lead program and Tagworks, the pioneer of Click-to-Release chemistry."

Anthony Tolcher, MD, FRCPC, CEO, Founder, and Director of Clinical Research of NEXT Oncology San Antonio and the TGW101 Phase 1 Primary Investigator commented, "TGW101 represents an attractive new potential treatment option in advanced solid tumors with high unmet need, overcoming certain challenges and limitations of other ADC therapies. TGW101 has the potential to offer an improved anti-tumor effect and safety profile which may lead to better clinical outcomes. I am excited to collaborate with Tagworks' team to evaluate TGW101 in patients with advanced solid tumors in the Phase 1 clinical trial."

In addition, Tagworks further strengthened its management team with the appointment of Keith Orford, MD, PhD, as CMO. Dr. Orford's proven track record as a physician, scientist, and executive leader at several biotechnology companies will support Tagworks' position as a leader and innovator in cancer drug development.

"We are pleased to welcome Keith and look forward to his contributions to the clinical development of our pipeline of innovative ADCs and targeted radiopharmaceuticals," said Ken Mills, Chief Executive Officer of Tagworks. "As we enter into clinical development, Keith's development expertise, strategic insights, and leadership in the oncology community will be critical in positioning Tagworks for long-term success."

"I am thrilled to join the experienced team at Tagworks to develop and expand on the transformative potential of the Click-to-Release technology with the clear goal of providing safe and efficacious new therapies for patients with cancer," said Keith Orford, MD, PhD, CMO of Tagworks. "I look forward to immediately working closely with all of our investigators to evaluate the therapeutic utility of TGW101 in multiple advanced solid tumor indications."

Dr. Orford brings extensive experience in leadership and oncology development, having served as CMO at public and private cancer biotechnology companies. Most recently, he was CMO, Executive Vice President, Clinical and Translational Science at Parabilis Medicines (formerly Fog Pharma), where he oversaw translational medicine and clinical development. Prior to Parabilis, he held a series of clinical development roles of increasing responsibility, including CMO of Calithera Biosciences, Clinical Development Lead and Clinical Head of Immuno-Oncology and Combinations DPU at GlaxoSmithKline, and Associate Director of Clinical Pharmacology and Experimental Medicine and Oncology at Merck. Before joining industry, he held various roles as a Research Fellow and Instructor at Massachusetts General Hospital and Harvard Medical School, where he trained in internal medicine and completed a postdoctoral fellowship. He received his BS, MD, and PhD from Georgetown University.

About TGW101
TGW101 is an antibody-drug conjugate (ADC) targeting TAG-72, a non-internalizing marker found on the surface of many solid tumor cells. TGW101 consists of a TAG-72-binding diabody conjugated with monomethyl auristatin E (MMAE) toxin. TGW101 is administered intravenous (IV) first and allowed to bind to TAG-72 in the tumor. Then a small molecule trigger is administered IV, resulting in selective chemical cleavage of the linker of the tumor-bound TGW101, release of the MMAE in the extracellular tumor microenvironment and diffusion into surrounding tumor cells. TGW101 is being studied in an open-label, multicenter, Phase 1 dose-escalation clinical trial designed to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy in patients with advanced solid tumors.

About Tagworks Pharmaceuticals
Tagworks Pharmaceuticals is 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 by targeting clinically validated tumor markers that so far have remained out of reach of current therapies. Its lead program, TGW101, is an antibody-drug conjugate (ADC) targeting TAG-72, a non-internalizing marker found on the surface of many solid tumor cells. Tagworks is developing a pipeline of novel cancer treatments leveraging its Click-to-Release technology in a range of therapeutics modalities, including ADCs and targeted radiopharmaceutical therapies. The Company is headquartered in the Netherlands with operations in the U.S. For more information, visit us at www.tagworkspharma.com.

SOURCE Tagworks Pharmaceuticals BV