I-Mab Reports Positive Interim Analysis from Phase 2/3 Study of its GM-CSF Antibody Plonmarlimab (TJM2) to Treat Patients with Severe COVID-19

I-Mab a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, announced positive interim data from its U.S. phase 2/3 study (NCT04341116) of plonmarlimab (also known as TJM2 or TJ003234) for the treatment of cytokine release syndrome (CRS) in patients with severe COVID-19. Plonmarlimab was discovered and developed by I-Mab to target human granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine that plays a critical role in acute and chronic inflammation.

COVID-19 virus (SARS-CoV-2), particularly the Delta variant, is known to cause a pathologic surge of circulating inflammatory cytokines termed cytokine release syndrome (CRS) or cytokine storm, which is responsible for complications and higher mortality associated with the disease. Plonmarlimab plays a critical therapeutic role in CRS through the inhibition of GM-CSF that acts at the upstream of the pathologic inflammatory cascade and is expected to be more efficacious in preventing and treating CRS.

“We are very excited about the data and plonmarlimab could be a very promising treatment for hospitalized patients with COVID-19,” said Deepa Gotur, MD, associate professor of clinical medicine at Houston Methodist.

The ongoing U.S. phase 2/3 study is one of the first double-blind, placebo-controlled, randomized studies to evaluate the therapeutic role of GM-CSF antibody in severe COVID-19 patients. The study aimed to determine the safety, efficacy and effects on cytokine levels following a single dose of 6 mg/kg of plonmarlimab or placebo in patients with severe COVID-19.

The current interim analysis showed positive preliminary results in patients who were mechanical ventilation free (MVF) at baseline (N=91). Plonmarlimab treatment resulted in a higher MVF rate (83.6% vs 76.7%) by day 30, lower mortality rate (4.9% vs 13.3%) by day 30, higher recovery rates (68.9% vs 56.7% at day 14 and 80.3% vs 70.0% at day 30), as well as reduced time to recovery and hospitalization duration, as compared to placebo. The magnitudes of the clinical improvements are comparable to those observed with lenzilumab in a similar patient population. Biomarker results were consistent with the observed clinical outcome and indicated patients treated with plonmarlimab had a reduction in plasma levels of pro-inflammatory cytokines and chemokines critically involved in CRS, including TARC, IP10, GCSF, IL10, IL6, MCP1, IL1RA, TNF-alpha but not interferon-gamma. A transient increase in Neutrophil to Lymphocyte Ratio (NLR) that is commonly associated with disease exacerbation was only observed in placebo. Plonmarlimab was well tolerated in all patients with no significant safety concerns.

“Plonmarlimab has shown very promising results from the interim data analysis in our phase 2/3 trial, and we intend to continue advancing the study in the U.S. at this critical juncture of the COVID-19 pandemic and continue exploring other clinical opportunities associated with CRS,” said Dr. Joan Shen, CEO of I-Mab.