Preclinical Candidates

Landos utilizes its LANCE platform to discover novel targets and continue developing disease specific therapeutic candidates that aim to address unmet needs for patients with autoimmune disease.

BT-104 is an oral, small molecule LANCL2 agonist in development for the treatment of systemic lupus erythematosus (SLE) and rheumatoid arthritis. Patients with SLE produce autoantibodies that result in inflammation and tissue damage. LANCL2 activation may intercept these evens upstream to allow maintenance of metabolic requirements for autophagy.

Rheumatoid arthritis is marked by over-activation of cells within the joint synovium. LANCL2 activation may results in a net decrease of inflammatory cell infiltration.

In preclinical studies to date, BT-104 reduced interferon gamma signaling in human SLE patient PBMCs in response to general, TLR7 and DNA antigens.

Landos expects to submit an IND for BT-104 for the treatment of SLE and rheumatoid arthritis in the second half of 2021.

BT-111 is an oral, small molecule LANCL2 pathway agonist in development for the treatment of nonalcoholic steatohepatitis (NASH) and type 1 diabetes. NASH results from activation and proliferation of fibroblasts in response to chronic inflammation caused by obesity, lipid accumulation and insulin resistance. LANCL2 activation may help to restore insulin sensitivity in obesity.

In Type 1 diabetes, insulin-producing pancreatic beta cells are destroyed, requiring life-long insulin replacement therapy. LANCL2 activation may help to restore self-tolerance and promote
glycemic control.

In preclinical studies to date of NASH, BT-111 decreased inflammatory responses and reduced markers of lipid accumulation and fibrosis.

Landos expects to submit an IND for BT-111 for the treatment of NASH and type 1 diabetes in the second half of 2021.

NX-66 is an oral, small molecule NLRX1 pathway agonist in development for the treatment of multiple sclerosis (MS) and Alzheimer’s disease. Multiple sclerosis is a chronic inflammatory, demyelinating and neurodegenerative disorder of the central nervous system. NLRX1 is uniquely positioned as the natural counterbalance to inflammatory NLRs that are overactive in MS, as well as contributing to the prevention of neurodegeneration.

Alzheimer’s disease is an inflammatory and neurodegenerative disease that causes dementia. NLRX1 activation may protect neurons from oxidative stress and ameliorate CNS inflammation in patients with this disease.

In preclinical studies to date, NX-66 protected against neuronal cell death upon stimulation with oxidative or inflammatory stress as well as deceased expression of inflammatory cytokines in the spinal cord and brain.

Landos expects to submit an IND for NX-66 for the treatment of MS and Alzheimer’s disease in the second half of 2021.

NX-73 is an oral, small molecule NLRX1 pathway agonist in development for the treatment of asthma and Chronic Obstructive Pulmonary Disease (COPD). Asthma encompasses a wide range of allergic and inflammatory diseases. NLRX1 activation may lessen the severity of disease through the innate immune system.

COPD is an inflammatory disease of the lung characterized by chronic bronchitis and emphysema and caused primarily by environmental exposures and cigarette smoke. NLRX1 activation may ameliorate alveolar destruction in patients with COPD.

In preclinical studies to date, NX-73 decreased TNF and interferon gamma producing CD4+ T cells in vitro.

PX-69 is an oral, small molecule PLXDC2 pathway agonist in development for the treatment of diabetic nephropathy and rheumatoid arthritis. Diabetic nephropathy is a main complication in both type 1 and type 2 diabetes and is the leading cause of ESRD. Activation of PLXDC2 may result in the downregulation of TNF, MCP1 and other cytokines, thereby helping to return the tissue to homeostasis in the deficiency of the native ligand.

Rheumatoid arthritis is characterized by a swelling and loss of mobility in joints caused by excessive inflammation and infiltration into the joint synovium. Activation of PLXDC2 has the potential to influence osteoclast genesis and angiogenesis in patients with rheumatoid arthritis.

In preclinical studies to date, PX-69 decreased TNF and IL-6 production from macrophages stimulated with LPS.