This technology centres around the development of bioactive peptide Adrenomedullin (AM) which consists of 52 amino acids.
Pilot clinical studies suggested that AM has a remarkable regeneration effect on the intestinal mucosa of patients with refractory inflammatory bowel disease. The team is developing AM and long-acting AM derivatives (Next-generation AM) to provide novel treatment with an approach that is completely different from existing drugs.
Technology Features, Specifications and Advantages
Adrenomedullin (AM) is a biologically active peptide ﬁrst isolated from human pheochromocytoma based on its potent vasodilatory activity. AM had an ameliorative effect in two experimental colitis models, acetic acid-induced colon ulcer, and dextran sulfate sodium-induced colitis. In addition to experimental models of inﬂammatory bowel disease (IBD), the pilot study evaluated the clinical feasibility of intravenous administration of AM in patients with refractory ulcerative colitis (UC).
Details of pilot study: Seven patients with active refractory UC participated and received intravenous infusion of AM for 8 h daily for 14 days, and their Disease Activity Index (DAI) were evaluated. DAI were improved in all patients after AM administration. Within 2 weeks, marked declines in DAI were observed in six patients, while a more modest decline was observed in one patient. Endoscopic examination revealed substantial amelioration of ulcers, with mucosal healing and scarring. Four patients remained in clinical remission 12 months after AM treatment. AM administration produced signiﬁcant increases in plasma AM concentrations (approximately 2.5-fold) that had a mild effect on blood pressure and heart rate, but with no serious adverse effects.
AM is a potentially useful agent that acts via a novel mechanism to safely induce mucosal healing and clinical remission in patients with refractory UC. The Next-generation AM is currently in development.
- Novel mechanism; mucosal healing (remodeling of damaged tissue) as well as anti-inflammatory.
- Safety of endogenous human peptide AM is higher than existing drugs.
New drug candidates for inflammatory bowel diseases, such as Ulcerative Colitis and Crohn's Disease.
- AM: Double-blind, placebo-controlled Phase2a clinical trials are ongoing in Japan.
- Next-generation AM: Preparing for First in Human study in 2020.
- IP: Issued patents of AM and pending applications of Next-generation AM.