Navitor’s discovery efforts leverage the potential to selectively modulate mTORC1 activity to address a broad range of diseases that are caused by dysfunctional mTOR activity.
Through selective targeting of mTORC1 activation, Navitor’s therapeutics have the potential to modulate either the catabolic or anabolic responses mediated by mTOR. This broad functionality presents unique opportunities for the development of novel product candidates that address a range of age-related diseases as well as several genetic and rare diseases linked to the dysregulation of mTORC1 signaling.
Navitor’s drug discovery efforts have identified compounds that can inhibit excessive mTORC1 activity in conditions with hyperactive response to nutrient signaling—such as metabolic, neurodegenerative, and autoimmune diseases; and age-related immune suppression (immunosenesence)—as well as compounds that can activate mTORC1 activity in conditions with reduced or suppressed response to nutrient signaling, such as musculoskeletal diseases.
Navitor’s therapies can ‘turn down’ over-activation of the mTORC1 pathway
Chronic Disease
Chronic Kidney Disease (CKD) Activation of mTOR within the kidney is observed in diabetic nephropathy and other forms of chronic and progressive kidney disease. Rapamycin treatment improves several key endpoints associated with loss of glomerular function, including glomerular hypertrophy, inflammation, and fibrosis.]However, long term therapy with rapamycin and analogs negatively impacts critical cell types important to kidney function due to mTORC2 inhibition.
Navitor’s proprietary Navalog program is uniquely suited for long term therapy in CKD due to the absolute selectivity for mTORC1 which should provide protection for critical kidney cell types
Type 2 diabetes, obesity and other metabolic diseases in which hyperactive mTORC1 activity is driven through the excess availability of nutrients and high plasma insulin concentrations, and is thought to cause dysregulated cellular function and accelerate the disease process.
Navitor’s mTORC1 inhibitors have the potential to improve insulin sensitivity and b-cell survival in metabolic diseases by specifically inhibiting the central process contributing to the nutrient-mediated pathology.
Progressive Disease
Alzheimer’s, Parkinson’s, and Huntington’s diseases and other neurodegenerative diseases that involve abnormal protein folding, possibly due to excessive and unrestrained protein synthesis.
Navitor’s mTORC1 inhibitors have the potential to restore more normal function by specifically inhibiting a central process contributing to the pathology of these diseases.
Rare Disease
Lymphangioleiomyomatosis (LAM) and Tuberous Sclerosis Complex (TSC) are rare diseases caused by specific genetic defects in the mTORC1 activation pathway, resulting in an uncontrolled hyperactivity of this complex that leads to abnormal cell and tumor growth.
Laminopathies (e.g., Progeria) are linked to increased mTORC1 activity. Selective inhibitors of mTORC1 may have utility in the management of these severe conditions.
Leigh’s syndrome, Friedrich’s ataxia, and other rare metabolic and mitochondrial diseases in which protein synthesis and/or cell growth have gone awry also involve hyperactive mTORC1 activation.
Navitor’s mTORC1 inhibitors have the potential to restore more normal function by specifically inhibiting the central process leading to these diseases.
Navitor’s therapies can ‘turn up’ reduced activation of the mTORC1 pathway
Brain Health
Depression, Cognitive Impairment/Memory and other neuropsychiatric disorders: stressors and other factors reduce mTORC1 signaling and thus neural synaptogenesis and synaptic signaling in key regions of the brain including the pre-frontal cortex and hippocampus which leads to a cascade of events that can result in depression, cognitive defects and memory problems.
Navitor’s lead clinical program, NV-5138, is a first-in-class, oral small molecule mTORC1 activator targeting the leucine nutrient sensor. NV-5138 directly activates the mTORC1 pathway in the brain leading to increased synaptogenesis, improved synaptic signaling and behavioral effects that last for up to 1 week in animal models. NV-5138 is in Phase 1 clinical testing for depression.
Muscle Health
Certain musculoskeletal conditions that involve muscle loss, such as, in the setting of glucocorticosteroid treatment, and due to aging, in which protein synthesis and/or cell growth is deficient.
Navitor mTORC1 activators have the potential to increase muscle protein synthesis and muscle function in multiple musculoskeletal indications.
