28 December 2018 - - China-based biopharmaceutical company Bio-Thera Solutions has filed an Investigational New Drug Application with the China National Medical Products Administration for the company's anti-Trop2 Antibody-Drug Conjugate, BAT8003, as a therapeutic agent for the treatment of Trop2 positive cancers, the company said.

Subject to NMPA acceptance, Bio-Thera Solutions plans to initiate the Phase I clinical trial early in 2019.

The planned Phase I trial will evaluate the safety, tolerability and pharmacokinetics of BAT8003 as a single agent in subjects with Trop2 positive cancers.

The first cohort of patients in the planned clinical trial will be enrolled in a standard [3+3] dose escalation regimen to assess safety and pharmacokinetics and to determine maximum tolerated dose of BAT8003.

Multiple dose expansion cohorts are planned with patients with Trop2 positive cancers, such as triple negative breast cancer and gastric cancer.

The primary objective of the dose expansion cohort is to confirm the safety and clinical activity of BAT8003 in patients with Trop2 positive cancers.

BAT8003 is an investigational Trop2-ADC being evaluated in multiple tumor types. BAT8003 utilizes Bio-Thera Solutions' proprietary linker-payload combination, Batansine.

The antibody component of the BAT8003 is engineered for site-specific conjugation to allow for better control of the ADC DAR providing a more homogenous product. The linker is non-cleavable ensuring superior delivery of the payload to the cancer cells and improving the safety profile of the ADC.

BAT8003 is being developed for use as a single agent and in combination with other agents for the treatment of Trop2 positive cancers.

Trop2, also known as tumor-associated calcium signal transducer 2 and trophoblast cell surface antigen 2, is a transmembrane glycoprotein that functions as an intracellular calcium signal transducer.

It signals cells for self-renewal, proliferation and invasion. While Trop2 is expressed in some normal tissues at low levels, Trop2 is overexpressed in many types of cancers and the overexpression of Trop2 is of prognostic significance.

Antibody-drug Conjugates or ADCs are designed to harness the targeting ability of monoclonal antibodies to deliver cytotoxic agents selectively to tumor cells by linking the monoclonal antibody and cytotoxic agent through a chemical linker.

An ideal ADC consists of a highly selective mAb for a tumor-associated antigen that has little or no expression on normal cells, a potent cytotoxic agent designed to induce target cell death after being internalized in the tumor cell and released and a chemical linker that is stable in circulation but releases the cytotoxic agent in target cells.

By selectively delivering a cytotoxic agent directly inside a tumor cell, ADCs increase the safety and tolerability of the cytotoxic agent relative to giving the cytotoxic agent systemically to the patient.

Bio-Thera Solutions is a specialist in next generation antibody discovery and engineering. The company has advanced five candidates into late stage clinical trials and has applied for marketing authorisation for one candidate.

In addition, the company has multiple promising candidates in early clinical trials and IND-enabling studies, focusing on innovative targets in immuno-oncology and autoimmune diseases.