- AMT-101, an oral GI-selective rhIL-10, showed potent activity at the site of disease in the colon in UC model with negligible systemic exposure
- Once daily, oral AMT-101 efficiently crossed the intestinal epithelium barrier, offering potentially improved pharmacokinetics and pharmacodynamics compared to systemically administered IL-10
South San Francisco, Calif., February 18, 2020 — Applied Molecular Transport Inc. (AMT), a clinical-stage biopharmaceutical company, today announced the presentation of preclinical data demonstrating the ability of AMT-101, an oral gastrointestinal (GI)-selective rhIL-10 fusion biologic therapeutic, to selectively target immunomodulatory pathways within the GI tissue to treat local GI-tissue inflammation, such as ulcerative colitis (UC), in a preclinical model of disease. The data were presented as an oral presentation in a plenary session by AMT’s co-founder and chief scientific officer, Randy Mrsny, Ph.D., at the European Crohn’s and Colitis Organisation (ECCO) held in Vienna, Austria on Saturday, February 15.
“Our AMT-101 preclinical data support the advancement of AMT-101 in the clinic and serve as an important validation of our technology platform that drives the active transport of therapeutic payloads across the intestinal epithelium barrier,” said Tahir Mahmood, Ph.D., Chief Executive Officer and Co-Founder of AMT. “Our clinical development of AMT-101 is initially focused on leveraging well-established IL-10 biology and we have a Phase 1b trial currently underway in ulcerative colitis.”
Following the conclusion of the Phase 1b trial, AMT plans to expand the development of AMT-101 beyond UC into other inflammatory bowel disease indications as well as peripheral inflammatory indications such as rheumatoid arthritis, that may benefit from the immunomodulatory and anti-inflammatory activity of an oral GI-selective rhIL-10 as well as its potentially enhanced safety profile.
These preclinical studies demonstrated increased intestinal epithelium (IE) barrier trafficking and intestinal localization of AMT-101 compared to systemic IL-10 administration, as well as improved pharmacokinetic and pharmacodynamic activity of AMT-101 compared to systemically administered biologics. AMT-101 was observed to effectively cross the IE barrier to reach the intestinal lamina propria and engage IL-10 receptors. Specifically, oral administration and localization of AMT-101 in the gut demonstrated efficacy in local GI tissues using preclinical models of colitis as well as showing systemic immunomodulatory benefits, as measured by the induction of IL-1Ra, a marker of anti-inflammatory activity and IL-10 pathway signaling, in systemic circulation.
AMT-101 is a GI-selective, oral fusion of rhIL-10 and its proprietary carrier molecule, currently in a Phase1b trial in UC. AMT-101 is designed to cross the IE barrier while not entering the bloodstream, thereby focusing the drug directly at the site of action of the underlying biology of the disease in the GI tissue and, therefore, potentially avoiding the side effects observed with systemic administration. By design, AMT-101 is actively transported through the IE barrier into the GI tissue, the primary site of inflammation in UC, a disease with approximately 2.2 to 2.4 million patients in the United States and Europe according to a 2014 report. As a locally-targeted, GI-selective biologic therapeutic, AMT-101 has potential use in a variety of inflammatory indications beyond UC.
About Applied Molecular Transport Inc.
Applied Molecular Transport Inc. (AMT) is a clinical-stage biopharmaceutical company leveraging its proprietary technology platform to design and develop a pipeline of novel oral biologic product candidates to treat autoimmune, inflammatory, metabolic, and other diseases. AMT’s proprietary technology platform allows it to exploit existing natural cellular trafficking pathways to facilitate the active transport of therapeutic payloads across the intestinal epithelium barrier. Active transport is an efficient mechanism that uses the cell’s own machinery to transport materials across the IE barrier. AMT believes that its ability to exploit this mechanism is a key differentiator of its approach. AMT is developing oral biologic product candidates in patient-friendly tablet and capsule forms that are designed for either targeting local GI tissue or entering systemic circulation to precisely address the relevant biology of a disease. AMT is building a portfolio of oral product candidates based on its technology platform including its lead product candidate, AMT-101, an oral GI-selective IL-10 that is currently in a Phase 1b clinical trial for UC. AMT plans to initiate multiple Phase 2 clinical trials of AMT-101 in UC and related inflammatory indications in 2020. AMT’s technology platform enables it to design and develop various oral biologic therapeutic modalities, such as peptides, proteins, full-length antibodies, antibody fragments, and RNA therapeutics, with potentially significant advantages over existing marketed and development-stage drugs. To learn more, please visit www.appliedmt.com.
Principal, Wheelhouse Life Science Advisors
Senior Partner, Wheelhouse Life Science Advisors