I-Mab and MorphoSys announced the first patient has been dosed in a phase 1 dose escalation study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TJ210/MOR210 monotherapy in patients with relapsed or refractory advanced solid tumors in the United States.

TJ210/ MOR210 is a monoclonal antibody developed by MorphoSys that is directed against complement factor C5a receptor 1 (C5aR1). Produced in the tumoral microenvironment, its ligand C5a acts as a chemoattractant to recruit tumor-promoting cells such as myeloid-derived suppressor cells, M2 macrophages and neutrophils. TJ210/MOR210 is designed to induce anti-tumor properties by blocking the activation and migration of C5aR1-expressing myeloid cells.

Preclinical studies have shown that targeting the C5aR-C5a axis exerts anti-tumor activity with immune checkpoint inhibitors. Furthermore, in vitro activity was observed for blocking the C5a/C5aR pathway also at very high C5a concentrations leading to a long duration of action. TJ210/MOR210 demonstrated a good safety profile with no observed adverse effects up to the highest dose tested in non-clinical safety studies.

The phase 1 clinical trial is an open-label dose escalation study with multiple doses in multiple centers in the U.S. to evaluate the safety, tolerability, and PK/PD of TJ210/MOR210 in subjects with advanced solid tumors. The development program will evolve into further clinical combination studies of TJ210/MOR210 with checkpoint inhibitors.

"We are encouraged by the data observed in the preclinical studies and believe that TJ210/MOR210 with its unique properties has great potential to target difficult-to-treat cancers," said Dr. Joan Shen, CEO of I-Mab. "The data generated from this study will provide valuable information about TJ210/MOR210's safety and tolerability profile and its potential benefits in patients with advanced cancers."

"We look forward to progressing with TJ210/MOR210 into clinical studies together with I-Mab to investigate its potential as a novel therapeutic option for patients with advanced solid tumors," said Dr. Malte Peters, Chief Research & Development Officer of MorphoSys.

MorphoSys will receive a $1.5 million payment from I-Mab for achieving this milestone under the license agreement between the two companies. MorphoSys and I-Mab entered into an exclusive strategic collaboration and licensing agreement to develop and commercialize TJ210/MOR210 in November 2018. Under the terms of agreement, I-Mab receives exclusive rights to develop and commercialize TJ210/ MOR210 in Greater China and South Korea, while MorphoSys retains rights in other parts of the world. With support from MorphoSys, I-Mab will also fund and conduct all global development activities of TJ210/MOR210, including clinical trials in China and the U.S., towards clinical proof-of-concept (PoC) in oncology.

TJ210/MOR210 is a novel human antibody directed against C5aR1 derived from MorphoSys's HuCAL Platinum? technology. C5aR1, the receptor of the complement factor C5a, is investigated as a potential new drug target in the field of immuno-oncology and autoimmune diseases. Tumors have been shown to produce high amounts of C5a, which, by recruiting and activating myeloid-derived suppressor cells (MDSCs), M2 macrophages and neutrophils, is assumed to contribute to an immune-suppressive pro-tumorigenic microenvironment. TJ210/MOR210 is intended to block the interaction between C5a and its receptor, thereby potentially neutralizing the immune suppressive function of C5a and enabling immune cells to attack the tumor.