I-Mab (NSDQ: IMAB), a Shanghai clinical-stage biopharma, has started to develop TJM2 (TJ003234) to treat cytokine release syndrome in severe cases of COVID-19. TJM2 is an I-Mab-discovered neutralizing antibody that binds human granulocyte-macrophage colony stimulating factor (GM-CSF), an important cytokine that plays a critical role in acute and chronic inflammation. By binding GM-CSF, TJM2 prevents downstream signaling and target cell activation, inhibiting other inflammatory responses. I-Mab intends to start clinical trials upon US acceptance of its IND. The company will expand the trials to countries especially hard-hit by COVID-19.

I-Mab said 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.

Cytokine storm is characterized by a surge in levels of circulating inflammatory cytokines, and is an overreaction of the immune system under conditions that include 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, especially the 20% of all patients whose disease requires intensive care.

I-Mab has completed a Phase I single ascending dose (SAD) study of TJM2 in the United States, in which TJM2 exhibited favorable safety, tolerability, PK/PD, and immunogenicity profiles. TJM2 also received IND clearance in China for a multiple-dose Phase Ib 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.

“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.”

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Disclosure: none.