I-Mab Biopharma is initiating the development of TJM2 (TJ003234) to treat cytokine storm in severe and critically ill patients caused by the coronavirus disease (COVID-19). TJM2 is an I-Mab-discovered neutralizing antibody against human granulocyte-macrophage colony stimulating factor (GM-CSF), an important cytokine that plays a critical role in acute and chronic inflammation.

The development will start following the U.S. Food and Drug Administration’s (FDA) acceptance of I-Mab’s Investigational New Drug (IND) application, and the study will commence initially in the United States with plans to expand into other hardest-hit countries.

Cytokine storm is characterized by surge of high levels of circulating inflammatory cytokines, and is an overreaction of the immune system under the conditions, such as CAR-T therapy and patients infected with SARS-CoV-2. Recent studies revealed that high levels of GM-CSF, along with a few other cytokines, are critically associated with severe clinical complications in COVID-19 patients. High concentration of GM-CSF was found in the plasma of severe and critically ill patients, which account for approximately 20% of all patients [3], especially in those requiring intensive care.

"Research data provide the rationale to use TJM2 as a potential treatment for cytokine storm associated with COVID-19, because the antibody effectively neutralizes circulating GM-CSF to control acute inflammatory responses, and it may also exhibit potential advantages over conventional IL-6 antibodies," said Dr. Joan Shen, CEO of I-Mab. "This expanded IND application of TJM2 would allow us to act timely to help battle the global COVID-19 pandemic."

The Company has successfully completed a Phase I single ascending dose (SAD) study of TJM2 in the United States, in which TJM2 has exhibited favorable safety, tolerability, PK/PD, and immunogenicity profiles. TJM2 also received IND clearance from China’s National Medical Products Administration for a multiple-dose Phase 1b study in patients with rheumatoid arthritis (RA). The results from the planned COVID-19 study will also be used to further evaluate the potential therapeutic role of TJM2 in reducing or preventing cytokine storm and neurotoxicity associated with CAR-T therapy.

TJM2 is an internally discovered neutralizing antibody against human GM-CSF, an important cytokine that plays a critical role in chronic inflammation and destruction in autoimmune diseases such as RA. GM-CSF can polarize macrophages into the pro-inflammatory M1 phenotype and is known to induce an inflammatory cascade involving other pro-inflammatory cytokines such as tumor-necrosis factor (TNF), interleukin-1 (IL-1), IL-6, IL-12, and IL-23. It is evident that GM-CSF plays a crucial role in the pathogenesis and disease progression of multiple autoimmune conditions.

TJM2 specifically binds to human GM-CSF with high affinity and can block GM-CSF from binding to its receptor, thereby preventing downstream signaling and target cell activation. As a result, it can effectively inhibit inflammatory responses mediated by macrophages, neutrophils, and dendritic cells, leading to reduced tissue inflammation and damage.

TJM2 is expected to be the first antibody of its class to enter clinic trials in China in 2020.

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