Landos Biopharma announces publication of results from first-in-human phase 1 study
Wednesday, May 15, 2019
Landos Biopharma, Inc., a clinical-stage biopharmaceutical company focused on the discovery and development of first-in-class, oral therapeutics for patients with autoimmune diseases, announced the publication of Phase 1 results of BT-11, its orally-active, gut-restricted investigational new drug (IND) for Crohn’s disease (CD) and ulcerative colitis (UC), in the IBD Journal published in association with the Crohn’s & Colitis Foundation. The first-in-human, Phase 1 single ascending dose (SAD) and 7-day multiple ascending dose (MAD) studies showed that BT-11 treatment is well-tolerated with no dose-limiting toxicities, and no detectable systemic immunosuppression up to daily oral doses of 100 mg/kg.
“The results of our Phase 1, first-in-human clinical study showed that the adverse event (AE) profile between placebo and BT-11 cohorts were comparable, and verified gut-restricted activity with minimal BT-11 systemic absorption, ” said Dr. Josep Bassaganya-Riera, Chairman and CEO of Landos. “These Phase 1 clinical results reinforce BT-11’s safety profile and show lower concentrations of fecal calprotectin, a predictive biomarker of therapeutic response and extended clinical remission in both UC and CD. These results support our plans to advance the evaluation of BT-11 to Phase 2 therapeutic efficacy studies in UC and CD patients.”
The publication, Safety, tolerability, and pharmacokinetics profile of BT-11, an oral, gut-restricted LANCL2 agonist investigational new drug for IBD: A randomized, double-blind, placebo-controlled Phase I clinical trial, was authored by researchers at Landos; the Icahn School of Medicine at Mount Sinai, NYC, NY; and Royal Adelaide Hospital, Adelaide, Australia. In the study, oral BT-11 was assessed for safety, tolerability and Pharmacokinetics in 70 normal healthy volunteers in a randomized, double-blind, placebo-controlled trial. Subjects were randomized into five single ascending dose cohorts (up to 100 mg/kg, p.o.) and three multiple ascending dose cohorts (up to 100 mg/kg QD for seven days, p.o.). Safety and tolerability were assessed by adverse event reporting, vital signs, ECG, hematology and clinical chemistry. BT-11 did not increase total or gastrointestinal AE rates relative to placebo, with no serious adverse events (SAE) observed. Oral BT-11 dosing did not result in any clinically significant findings by biochemistry, coagulation, ECG, hematology, or urinalysis when compared to placebo.
Additional details from the study:
• The study found that fecal concentrations of BT-11 were 6,000-fold higher than maximum plasma concentrations. We believe this gut-restriction in humans validates the local actions of BT-11 observed preclinically in animal models, in which plasma concentrations of BT-11 were less than 0.1% of fecal concentrations.
• BT-11 did not induce any effect on vital signs, cardiovascular or respiratory function, no systemic immune effects were observed. Clinical laboratory results additionally support a lack of hepatic and renal toxicities in the study.
• BT-11 did not result in a decrease in White Blood Cell count or other hematology related parameters, which suggests that given its gut-restricted activity, BT-11 may reduce or avoid systemic immunosuppression. These initial results are consistent with findings from nonclinical studies and suggest a lower risk for systemic immunosuppression with BT-11 as opposed to systemic IBD drugs.
• Doses of 7-14 mg/kg in the form of a once daily tablet are expected to be evaluated in Phase II studies in IBD patients for therapeutic effect. The results of this Phase 1 study suggest a wide safety margin (7- to 15-fold compared to clinical doses to be studied) in human subjects.
• Fecal calprotectin is believed to be a predictive biomarker in IBD, is a key diagnostic test for differentiating UC and CD from IBS. Over 99% of IBD patients have elevated calprotectin and is predictive of relapse. In this study, fecal calprotectin levels were lower in all BT-11 treated groups when compared to placebo.