SynOx Therapeutics has announced the dosing of the first patients in its Phase 3 registrational study, TANGENT, evaluating emactuzumab for the treatment of Tenosynovial Giant Cell Tumour (TGCT). The company also completed a final close of its Series B financing, raising a total of $92 million to support the trial.
The TANGENT trial (NCT05417789) is a global, multi-center, randomized, double-blind, placebo-controlled Phase 3 trial designed to assess the efficacy and safety of emactuzumab in patients with TGCT. The primary outcome measure is overall response rate (ORR). Secondary outcomes include functional and quality of life measurements, impact on tumor volume, and duration of response. Approximately 130 patients are expected to enroll in the trial.
Emactuzumab: A CSF-1R Inhibitor
Emactuzumab is a humanized IgG1 CSF-1R targeted antibody that inhibits and depletes macrophages in the tumor tissue. It targets the CSF-1 receptor (CSF-1R), which is expressed on macrophages and certain other cells, affecting their production, differentiation, and function. TGCT is driven by excessive production of CSF-1, making CSF-1R a key target for therapeutic intervention.
Tenosynovial Giant Cell Tumour (TGCT)
TGCT is a rare, non-malignant but aggressively growing tumor of the synovium, primarily located in knee, hip, and ankle joints. It is a chronically debilitating disease causing loss of function of the affected joints, pain, stiffness, and limited range of motion. Current treatments often involve surgical intervention, but recurrence rates post-surgery can be high, exceeding 50% at three years.
Clinical Data and Potential
Previous clinical studies of emactuzumab as a monotherapy in 63 patients with TGCT have demonstrated a substantial effect on tumor response, with an ORR of approximately 71%, while also being well-tolerated. These earlier phase I/II studies indicated good tolerability, a manageable safety profile, and substantial preliminary efficacy in TGCT patients, characterized by rapid, robust tumor reduction, clinical benefit, and durable response.
Leadership Commentary
"We are pleased to add Gilde Healthcare to our impressive investor syndicate and are appreciative for their support of our team and our vision for the potential of emactuzumab to address the unmet needs, and improve the quality of life, of TGCT patients around the world," said Ray Barlow, Ph.D., Chief Executive Officer of SynOx. Arthur Franken, general partner at Gilde Healthcare, added, "We are pleased to join SynOx as an investor and help support the late-stage development of emactuzumab, which we believe has a best-in-class profile as a CSF-1R targeted antibody."
