Evelo Biosciences Announces Biomarker Data Showing Drug is Orally Delivered Dual Cytokine Inhibitor for Inflammatory Diseases

Evelo Biosciences, Inc. recently announced biomarker data for EDP1815, its lead inflammation product candidate. Interim data from individuals in the ongoing Phase 1b clinical trial showed marked activity on multiple individual systemic markers of inflammation, including interleukin-6 (IL-6) and interleukin-8 (IL-8). IL-6 and IL-8 are well-established mediators of potentially harmful effects in patients with inflammatory diseases and these data support the therapeutic potential of EDP1815 to treat classic inflammatory diseases such as psoriasis.

“These results support our central thesis that we can treat systemic inflammation by targeting SINTAX, the small intestinal axis. This radical new understanding of how inflammation is controlled is the foundation of our approach to developing effective, safe, orally delivered medicines,” said Mark Bodmer, PhD, Chief Scientific Officer of Evelo. “This analysis of specific clinical biomarkers provides further evidence that EDP1815 has the potential to address systemic inflammation by targeting the functional connections in the small intestine with the rest of the body. Concurrent reductions in the production of multiple inflammatory cytokines by a well-tolerated oral agent is a unique profile for the treatment of diseases involving inflammation.”

Evelo previously reported interim data showing reduced production of systemic markers of inflammation in individuals with mild-to-moderate psoriasis dosed with EDP1815. The detailed analysis of the previously reported data show that EDP1815 highlights the individual inflammatory cytokines and chemokines that were modulated.

Six cytokines were reliably detected in the biomarker assay. The results for IL-6 and IL-8 are shown in the waterfall plots below. Treatment with EDP1815 caused a pronounced downward shift in production compared to placebo during the 28-day treatment period. Similar, slightly less pronounced reductions were seen for TNFa and IL1b. No effect was seen on IFN-g or IL-10.

Evelo plans to study EDP1815 in a range of inflammatory diseases following interim data from a planned Phase 2 trial in psoriasis, expected in late 2020. The effect of EDP1815 on IL-6 and IL-8 induction is also notable given the emerging evidence of their potential role in driving pathogenic effects and lung damage following infection with a range of viruses including influenza, coronaviruses (SARS, MERS and SARS-CoV-2), and respiratory syncytial virus. Based on these new biomarker data, Evelo is in the early stages of evaluating opportunities to develop EDP1815 for the treatment of diseases caused by viral infection, including influenza and coronaviruses (SARS-CoV-2).

Blood samples were taken at baseline and after 28 days of daily oral administration of EDP1815 (n=20) or placebo (n=18) from patients in Evelo’s ongoing clinical study in mild to moderate psoriasis. Whole blood was incubated with a broad inflammatory activator, lipopolysaccharide (LPS). The waterfall plots show the difference between the baseline value and after 28 days of treatment. All patients from both low and high dose EDP1815 cohorts are shown.

Evelo Biosciences is a clinical-stage biotechnology company developing oral biologics that act on SINTAX, the small intestinal axis, with systemic therapeutic effects. SINTAX plays a central role in governing the immune, metabolic, and neurological systems. The company’s first product candidates are monoclonal microbials, single strains of microbes selected for defined pharmacological properties. Evelo’s therapies have the potential to be effective, safe, and affordable medicines to improve the lives of people with chronic diseases and cancer. Evelo currently has four product candidates: EDP1815, EDP1867, and EDP2939 for the treatment of inflammatory diseases, and EDP1503 for the treatment of cancer. Evelo is also advancing additional oral biologics through preclinical development in other disease areas. For more information, visit www.evelobio.com.