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Small Molecule to Be Evaluated for Treatment of CAR-T-related Cytokine Release Syndrome

Poolbeg Pharma’s POLB 001 previously showed promise in a lipopolysaccharide human challenge trial.

Poolbeg Pharma has announced its intention to pursue an expanded indication for POLB 001, a small molecule immunomodulator originally developed to address hypercytokinemia in severe influenza, for the treatment of cytokine release syndrome (CRS) in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of hematological cancers.1,2

POLB 001 is intended to inhibit p38 MAP kinase in order to reduce expression of cytokines, including IL-6 and TNFα, which can damage tissue.3 POLB 001 recently demonstrated promising safety and efficacy in initial data from a phase 1 clinical trial evaluating the drug in 36 healthy volunteers aged 18 to 55 years who were challenged with bacterial lipopolysaccharide (LPS), intended to simulate a hyperinflammatory response from severe influenza or other diseases.2,3 Poolbeg reported that the participants in the randomized, double-blind trial who received POLB 001 achieved a “marked reduction in both systemic and localized inflammatory response.”2,3 It was additionally noted that responses showed a dose-dependent relationship. In terms of safety, POLB 001 was well-tolerated with no serious adverse events observed and no participants choosing to voluntarily withdraw.

"Following the completion of the LPS human challenge trial in December, we are excited to see this positive initial data of POLB 001,” Jeremy Skillington, chief executive officer, Poolbeg Pharma, said in a statement.2 “The clear anti-inflammatory dose response, with no serious adverse events, further demonstrates the strong potential for POLB 001 to address the significant unmet medical need in severe influenza and beyond. We look forward to presenting the full data in Q2 2023.”

In light of data gathered during the research for the severe influenza indication, which Poolbeg Pharma described as specific to the immune response in patients receiving CAR-T, the company determined that POLB 001 could serve as a potential treatment for CRS caused by CAR-T, and submitted a patent application related to the use of p38 inhibitors for this indication.1 Poolbeg is now performing research with the intention of enabling a clinical trial for the evaluation of POLB 001 in patients receiving CAR-T for the treatment of cancer. The company expects to be able to initiate a clinical trial in 2024, with updates on data and progress towards this goal expected later this year.

"Hyperinflammation as a driver of disease severity in influenza is also fundamental to CRS, which can severely complicate CAR-T cell therapy of patients with blood cancers,” Brendan Buckley, Scientific Advisory Board member, Poolbeg Pharma, said in a statement regarding the news.1 “By reducing runaway inflammation associated with CRS, POLB 001 has the potential to significantly reduce the serious adverse effects that many CAR-T cell patients suffer...With oncology clinical trial enabling activities for POLB 001 underway, we look forward to updating the market as to the progress of this exciting program."

1. Poolbeg announces strategic expansion of POLB 001 into oncology. News release. Poolbeg Pharma. January 16, 2023. https://polaris.brighterir.com/public/poolbeg_pharma/news/rns_widget_home/story/xel2nzr 
2. Positive initial data analysis in POLB 001 LPS challenge trial. News release. Poolbeg Pharma. January 9, 2023. https://polaris.brighterir.com/public/poolbeg_pharma/news/rns/story/w69767w 
3. Poolbeg Pharma. POLB 001 – severe influenza. Website Accessed January 16, 2023. https://www.poolbegpharma.com/pipeline/polb-001/