Benzinga | Nov 10, 2020 08:14AM EST

Applied Molecular Transport Highlights Publication Of Preclinical Data Demonstrating Potential Of Novel Oral IL-10 Biologic Therapeutic For Inflammatory Diseases In The Journal Of Immunology

- AMT-101 (oral fusion protein of hIL-10 and AMT carrier) rapidly and efficiently transports through intestinal epithelia in healthy and inflamed conditions to target local intestinal tissue -

- Demonstrates minimal systemic exposure of hIL-10 while driving induction of an anti-inflammatory profile correlated with hIL-10 in rodent and non-human primate models -

- Acts on macrophage cells and lymphocytes within intestinal tissue leading to efficacy outcomes in colitis models -

SOUTH SAN FRANCISCO, Calif., Nov. 10, 2020 (GLOBE NEWSWIRE) -- Applied Molecular Transport (NASDAQ:AMTI) (AMT), a clinical-stage biopharmaceutical company, today announced that the unique mechanism of action of AMT-101 and preclinical data supporting its potential as a treatment for ulcerative colitis (UC), and other inflammatory diseases, have been published in The Journal of Immunology. The article entitled, "A Novel Fusion of Interleukin-10 Engineered to Traffic Across Intestinal Epithelium to Treat Colitis" was published in the November 2020 online edition of The Journal of Immunology.

The research published in The Journal of Immunology highlights how AMT's proprietary technology platform exploits existing natural cellular trafficking pathways to actively transport therapeutics through the intestinal barrier directly into the underlying immune-rich milieu of the lamina propria. IL-10 is a potent immunomodulatory cytokine with significant therapeutic potential in intestinal inflammatory diseases as well as in those associated with systemic inflammation. However, clinical utilization of IL-10 to treat inflammation and immune-dysregulation has been limited due to side effects associated with systemic administration.

"Our breakthrough platform technology enables the active transport of oral biologics by solving the long-standing industry challenge of transporting large, biologically-active molecules efficiently across the intestinal barrier," said Randall Mrsny, Ph.D., chief scientific officer and co-founder of AMT. "Our technology platform is based on native, active vesicular transcytosis mechanisms to rapidly and efficiently traverse intestinal epithelial cells. Once across this epithelia barrier and in the underlying intestinal lamina propria, AMT-101 targets local macrophages and lymphocytes to activate cell signaling pathways, inducing tissue and circulating markers demonstrating IL-10 mechanism of action through cognate receptor engagement and down-stream signaling. Importantly, we continue to leverage our technology platform to be a robust engine for the design and development of a wide range of oral biologic therapeutics."

In vitro and in vivo characterization of AMT-101 demonstrated its ability to efficiently cross the human intestinal epithelium by an active, receptor-mediated vesicular transcytosis process, activating IL-10 receptor signaling to increase cellular phospho-STAT3 (pSTAT3) levels in macrophage cells. In models of induced colitis, AMT-101 was able to rectify pathologic changes by suppressing pro-inflammatory markers of disease while inducing anti-inflammatory cytokines, both locally in the intestinal tissue as well as in plasma.

"Our preclinical data has also shown that oral hIL-10 can be targeted to the intestinal lamina propria with minimal systemic PK, suggesting that we may be able treat IBD patients with fewer toxicities than previously observed following the systemic administration of this potent cytokine," said Tahir Mahmood, PhD, chief executive officer and co-founder of AMT. "We have evaluated AMT-101 in active ulcerative colitis patients in a Phase 1b study and demonstrated reductions in objective clinical measures of intestinal inflammation such as fecal calprotectin and histopathologic scores, as well as systemic indicators of inflammation such as C-reactive protein, after just 14 days of treatment. We are excited about our ongoing and planned Phase 2 trials for AMT-101 in IBD and rheumatoid arthritis and will continue to leverage the platform to build our pipeline of differentiated oral biologic therapeutics."