Omilancor Exerts Anti-Inflammatory Effects Within the Gastrointestinal Tract
Omilancor (BT-11), our lead product candidate, is a first-in-class, gut-restricted oral therapeutic candidate that targets LANCL2, a membrane receptor that has been shown to modulate immunological mechanisms that are associated with various autoimmune diseases such as ulcerative colitis (UC) and Crohn’s disease (CD).
In 2021, Landos announced final results from its Phase 2 proof-of-concept trial of omilancor in patients with mild-to-moderate UC. The results demonstrated that omilancor was gut-restricted and well tolerated, with a similar adverse event profile across placebo and omilancor groups. In addition, omilancor induced placebo-adjusted clinical remission rates of up to 11.5% at week 12, with normalization of biomarkers such as fecal calprotectin observed after two weeks of oral dosing. Based on clinical data to date, omilancor may address the main limitations of current therapies by providing a convenient once a day dosing that offers low systemic exposure, improved tolerability and no ties to toxicities. Following a positive outcome from an End-of-Phase 2 meeting with the U.S. FDA, Landos and the FDA agreed on key elements necessary for regulatory approval.
NX-13 Modulates Epithelial Integrity and Mucosal Immune Responses in the Gastrointestinal Tract
NX-13 is a first-in-class novel, gut-restricted oral therapeutic candidate that targets NLRX1 (NOD-like receptor X1), a mitochondria-associated receptor that has been associated with the modulation of inflammatory cytokines for UC and CD.
In March 2021, Landos reported positive results from a Phase 1a trial of NX-13 in healthy volunteers, for which all primary and secondary endpoints in safety and tolerability were achieved. In April 2021, Landos initiated a Phase 1b trial to evaluate the safety and pharmacokinetics of multiple dose levels of NX-13 in patients with UC.
LABP-104 Aims to Enhance Tolerability and Restore Homeostasis in Immune Cells
LABP-104 is an oral, small molecule LANCL2 agonist in development for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other debilitating and widespread autoimmune diseases.
Patients with SLE commonly produce autoantibodies that result in inflammation and tissue damage. LANCL2 activation intercepts these events upstream through the induction of regulatory T cell (Treg) responses and support of metabolic requirements for autophagy. LABP-104 has reduced type I interferon signaling in human SLE patient peripheral blood mononuclear cells (PBMCs) in response to general, TLR and DNA antigens. In addition, oral treatment with LABP-104 maintained kidney function, reduced anti-nuclear antibody formation and shifted the balance of CD4+ T cells from effector or inflammatory subsets to protective Tregs in the spleen.
In animal models of RA, activation of the LANCL2 pathway has resulted in decreased tissue-damaging Th17 and Tfh cells with increased protective Tregs.
Landos initiated a Phase 1 trial of LABP-104 for the treatment of SLE and RA in healthy volunteers in October 2021, with topline data readout expected in the first half of 2022.