I-Mab announced interim results from a multi-center, double blinded, randomized, placebo-controlled, three-arm clinical study of TJM2 in patients with cytokine release syndrome (CRS) associated with severe coronavirus disease 2019 (COVID-19).

TJM2, also known as TJ003234, 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 tissue inflammation. This study adopts a robust clinical trial design and represents one of the first double-blind, placebo-controlled and randomized studies to evaluate the therapeutic role of anti-GM-CSF antibody in severe COVID-19 patients. I-Mab has followed a rigorous and robust clinical trial protocol, the first among similar anti-GM-CSF antibody studies globally, to ensure robustness of the study conclusion and data integrity.

"I-Mab's carefully planned clinical trial of its novel anti-GM-CSF agent brings potential new hope to effectively treat severe SARS-CoV-2 infection by suppressing uncontrolled inflammation", said Dr. Marcel Curlin, M.D., Associate Professor, Department of Medicine, Division of Infectious Diseases, Oregon Health and Sciences University. "Preliminary results and positive review from the DMC are encouraging, and if we now begin to see an efficacy signal, we will have a powerful new approach to treating severe disease due to COVID-19."

"As an innovative global biotech company, I-Mab has a responsibility to help address the urgent global health crisis. Since the outbreak took place, we sprang into action to prioritize TJM2 in response to the urgent medical needs. It is clear that the rationale and expectation of our study is further supported by the preliminary and encouraging evidence from other pilot studies with GM-CSF antibody class for this clinical indication," Dr. Jingwu Zang, M.D., Ph.D., Founder and Honorary Chairman and Director of I-Mab said.

Part 1 of the study evaluated the safety and tolerability of TJM2 in a total of 24 patients who were randomized at a ratio of 1:1:1 to receive either a single dose of 3 mg/kg TJM2, a single dose of 6 mg/kg TJM2 or placebo (standard care), administered by intravenous (IV) infusion. Data from Part 1 of the study were reviewed by a DMC to assess patient safety and overall conduct of the study. After comprehensive review and analysis, the DMC concluded that I-Mab can commence the Part 2 of the study as planned, indicating TJM2 is safe and well-tolerated in the severe COVID-19 patients in the study. The DMC also endorsed protocol changes, including broadening the inclusion criteria and dosing all patients at 6 mg/kg of TJM2 or placebo.

Part 2 of the study with a similar design to Part 1 will target the same patient population and is expected to be initiated shortly. It will evaluate the efficacy, safety and cytokine levels following a single dose of 6mg/kg TJM2 or placebo in 120 patients with severe COVID-19.

"We appreciate DMC's assessment and positive recommendation which is a testament to I-Mab's science-focused clinical development capabilities," said Dr. Joan Shen, MD, PhD, CEO of I-Mab. "We are committed to conducting a robust clinical trial to the highest standards and we believe we have the most advanced anti-GM-CSF study in COVID-19 that could potentially lead to registration of TJM2 in the U.S. The DMC's confirmation of TJM2's safety profile bolsters the drug's potential to address the complications among the severe and critically ill – and ultimately save lives."

The emerging data indicate that the common features among COVID-19 patients particularly those severely or critically ill include lymphopenia and significantly elevated serum levels of pro-inflammatory cytokines including GM-CSF and IL-6, IFN-gamma. Moreover, recently published data indicate that COVID-19 can induce a cytokine storm instigated by extensive immune cell infiltration and the release of GM-CSF and IL-6[3]. These inflammatory cytokines drive aberrant activation of monocytes and lymphocytes which in turn provoke increased production of more cytokines and chemokines in a feed forward cycle, resulting in the cytokine storm, or CRS, severe pulmonary complications and mortality. Therefore, blocking of GM-CSF by TJM2 may impact the upstream of cytokine storm network to prevent or curb the hyperinflammation and immunopathology which may be responsible for the complications associated with severe COVID-19.

According to the WHO, as of May 26, 2020, there were 5,404,512 confirmed cases and 343,514 deaths of COVID-19 globally. Severe and critically ill patients account for approximately 20% of all diagnosed patients.