Phase 2 Proof-of-Concept Efficacy of BT-11 in Crohn?s Disease Patients Landos Biopharma is a clinical-stage biopharmaceutical company focused on the discovery and development of innovative first-in-class oral therapeutics for patients with autoimmune diseases. Our lead asset, BT-11, is a novel oral, gut-restricted investigational new drug (IND) targeting the Lanthionine Synthetase C-Like 2 (LANCL2) pathway in the gut during inflammatory bowel disease (IBD). An unmet clinical need for safer, more effective IBD drugs remains, as current therapies have limited efficacy and adverse side effects. The Technology & Product. Landos designed BT-11, a new chemical entity, to activate the LANCL2 pathway selectively within the gastrointestinal (GI) tract for the treatment of Crohn?s disease (CD). BT-11 activation of LANCL2 functions through a dual upregulation of regulatory responses and downregulation of inflammatory responses. BT-11 efficacy is proven in 5 mouse models of IBD and translational studies in primary human PBMCs and LPMCs. BT-11 is primarily localized to the GI with a NOAEL of >1,000 mg/kg in 3-month GLP rat and dog toxicity studies. The BT-11 program has 2 open INDs (138071 & 128490), completed Phase I clinical testing in 2018 and initiated a Phase 2 clinical study in mild to moderate UC patients in August of 2019.
The Specific Aims for the R01 application are to: (1) Evaluate the blood and fecal PK profiles of BT-11 in CD patients. Blood samples will be collected at 16 timepoints (pre-dose, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 48 h) on days of the first dose and the seventh dose. Fecal samples will be collected daily. Plasma and feces will be processed and analyzed for systemic and gut BT-11 concentrations. (2) Validate PD biomarkers of BT-11 activity in CD patients. Using samples generated from the 14-d Phase 1b study, we will measure the concentration of C-reactive protein, TNF?, IFN?, IL-6, and IL-10 in plasma and calprotectin and lactoferrin in feces. (3) Perform a proof-of-concept study to assess efficacy and mechanisms of BT-11 in CD patients. Moderate to severe CD patients will be treated with for 12 wk with oral tablets containing 1,000 mg BT- 11 or placebo (n=20 per arm). Subjects will be monitored at baseline, 2, 6, and 12 wk to assess symptoms and collect blood and feces with endoscopy at baseline and 12 wk. The primary successful outcome will be an induction of clinical remission and endoscopic response. Secondary outcomes will include: >1 mg/g concentration of BT-11 in feces, reduction of plasma CRP and fecal calprotectin by BT-11 treatment, and decrease in inflammatory cytokines in plasma. The long-term goal of Landos? technology is to develop safer, more effective first-in-class oral therapeutics for IBD that address an unmet clinical need for a market exceeding $10 billion and growing 25% annually.
The two clinical manifestations of inflammatory bowel disease (IBD), Crohn?s disease (CD) and ulcerative colitis (UC), afflict over 2,000,000 people in the United States and 5,000,000 people worldwide. This R01 application builds on the successful nonclinical development and Phase I clinical testing of BT-11, an investigational new drug that targets lanthionine synthetase C-like 2 (LANCL2) for treating IBD. Based on the successful filing of two INDs for the clinical investigation of BT-11 in UC and CD, this project will advance BT-11 into proof-of-concept Phase 2 clinical testing in CD patients with moderate to severe disease.
