About Us
Aeovian Pharmaceuticals is a clinical-stage biopharmaceutical company developing targeted and highly selective small molecules to restore cellular metabolic quality control, thereby addressing the dysregulated growth and hyperactive signaling found in certain rare genetic and age-related diseases.
Our lead development candidate, AV078, is a first-in-class CNS-penetrant selective inhibitor of mTOR complex 1 (mTORC1) being developed for the treatment of tuberous sclerosis complex (TSC) refractory epilepsy. TSC is a rare genetic disorder caused by the hyperactive signaling of mTORC1.
Beyond AV078, we have developed a proprietary library of small molecules, which are potent and selective inhibitors of either mTORC1 or CD38, and have the potential to precisely target the underlying biology of multiple rare and age-related diseases.
Our Science
Mechanistic target of rapamycin (mTOR) is an evolutionarily conserved kinase that serves as the catalytic center of two distinct protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).
These complexes serve as fundamental regulators of incoming environmental and nutritional signals, and finely regulate anabolic and catabolic functions to maintain healthy cellular homeostasis.
In healthy individuals, mTORC1 and mTORC2 are in balance. In TSC, pathogenic mutations in TSC1 or TSC2 cause loss of function of the normal role of the TSC complex in inhibiting mTORC1, thereby leading to selective overactivation of mTORC1 activity. This results in dysregulation of multiple physiologic processes including cellular growth and proliferation and protein synthesis, which can cause a variety of hamartomas or tumors affecting multiple organ systems, primarily the brain, kidney, heart, eyes, lungs, and skin. In addition, patients with TSC frequently develop epilepsy, and may be affected by varying degrees of developmental delay and neuropsychiatric problems such as autism.
Epilepsy can affect approximately 90% of patients with TSC, and mTORC1 overactivation appears to prominently contribute to pathophysiology, including dysregulation of cellular growth control and neuronal excitation/inhibition imbalance, implicating genetically driven hyperactive mTORC1 signaling as a root cause of epilepsy associated with TSC. It is estimated that approximately two thirds of patients with TSC will develop medically intractable epilepsy. Recurrent seizures can contribute to intellectual and developmental disabilities and an increased risk of injury and death, creating a substantial unmet need for development of new treatment options for managing intractable epilepsy in patients with TSC.
Rapamycin and its previously developed analogs functionally result in nonselective inhibition of mTORC1 and mTORC2, and this nonselective profile has been associated with tolerability issues that have limited their use. The nonselective mTORC1/mTORC2 inhibitor everolimus has demonstrated a partial degree of efficacy in TSC epilepsy, but its clinical use has been limited due to dose-limiting toxicities which often result in dose reductions or interruptions which in turn limit achievable efficacy. The suboptimal safety and efficacy profile of nonselective mTORC1/mTORC2 inhibitors has resulted in a significant ongoing unmet medical need for a next-generation treatment able to achieve improved safety and efficacy by selectively targeting the mTORC1 overactivation associated with TSC. As such, we believe TSC is an exceptionally clear and compelling precision medicine target for AV078, our first-in-class CNS-penetrant selective inhibitor of mTORC1.
Our Pipeline
