I-MAB advances repositioned RA drug in early trial to treat COVID-19 cytokine storm

I-Mab Biopharma management
I-MAB Biopharma's executives are consulting with regulators to develop a plan for speeding their anti-inflammatory drug TJM2 to market to treat COVID-19 cytokine release syndrome. (I-Mab Biopharma)

Several weeks after the COVID-19 pandemic rolled across the globe, the term “cytokine storm” started popping up in medical reports from physicians treating the disease. The emergence of the syndrome—a hyperactive immune response that can be deadly—prompted several companies to scour their product portfolios and pipelines for drugs that might be able to target it.

China-based I-MAB Biopharma, fueled by a recent $104 million initial public offering, has joined the effort to speed medicines to market that can treat cytokine release syndrome. The company said last week that it saw positive results from a small clinical study of its experimental drug TJM2 and is progressing to part two of the study.

TJM2 is an antibody that inhibits GM-CSF, a cytokine that’s known to contribute to tissue inflammation and degeneration in diseases such as rheumatoid arthritis (RA). It’s a different mechanism of action than Roche’s Actemra, which is an IL-6 inhibitor that has been snapped up during the pandemic to treat patients with cytokine release syndrome.

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In part one of I-MAB’s trial, 24 patients were randomized to receive one of two doses of TJM2 or a placebo. The company didn’t provide many details about the results except to note a “correlation between clinical improvement and reduced levels of some disease related cytokines.”

The higher of the two doses of TJM2 will be tested against a placebo in the next phase of the study, which will include 120 patients, the company said. I-MAB recently completed a phase 1 safety study of the drug in healthy volunteers in the U.S.

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Studies of COVID-19 patients have documented high levels of both GM-CSF and IL-6 in the bloodstream of those who become severely ill, said Jingwu Zang, founder of I-MAB, in a conference call with analysts about the clinical trial plan. “While our goal remains to develop TJM2 in rheumatoid arthritis and other autoimmune conditions, there is strong scientific evidence to suggest that inhibiting GM-CSF may have a beneficial impact on patients with cytokine release syndrome … associated with COVID-19,” he said.

I-MAB does have an IL-6 inhibitor in phase 2 trials to treat ulcerative colitis and other diseases, leading one analyst to ask during the call why the company chose to pursue TJM2 in COVID-19 instead.

“In terms of the mechanism of action, GM-CSF works upstream in the pro-inflammatory cytokine network,” Zang said. “It sits above IL-6. So targeting GM-CSF not only inhibits IL-6, but also other inflammatory cytokines that play an important role in cytokine release syndrome.”

I-MAB will face some competition from other companies stepping up to address cytokine release syndrome in COVID-19. In mid-May, Roivant Sciences said it has seen positive signals from a 56-patient trial of its GM-CSF inhibitor, gimsilumab, in treating COVID-19 patients with lung injuries. The company is continuing the trial and amending it to include patients who are being treated with antivirals or plasma from survivors.

There are multiple other approaches being examined for controlling cytokine release syndrome in COVID-19. In April, the FDA granted emergency approval to a device that strips inflammatory cytokines out of the blood. Novartis and Incyte are testing their JAK inhibitor Jakafi for treating the syndrome, and Roche said last week it would launch a trial combining Actemra with Roche’s recently approved remdesivir in patients with severe COVID-19 pneumonia.

I-MAB may not be as big a name as other COVID-19 players, but it does have a large network of backers. Prior to its January IPO, it raised more than $400 million from C-Bridge Capital, CDH Investment and several other private investors who were attracted to its strategy of advancing multiple phase 2 and 3 trials simultaneously.

I-MAB’s executives said during the call that if the results of part two of the TJM2 study in COVID-19 are positive, it will consult with the FDA to develop a plan to speed the drug to market. The company is also accelerating a manufacturing plan to ensure it will have enough of the drug for further clinical trials and to meet the public demand, they said.

Editor's note: This story has been updated with details from Roivant Sciences.

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