Initial focus on epilepsy could drive progress in aging and healthspan therapeutics targeting the mTOR pathway.
US biotech Aeovian Pharmaceuticals today secured a $55 million Series B funding round to advance its lead program in a rare form of epilepsy – a move that could ultimately shape how longevity-linked mTOR biology is therapeutically harnessed in aging and healthspan. The oversubscribed round, led by Luma Group, will fund completion of a Phase 2 proof-of-concept study of AV078, a selective mTORC1 inhibitor in tuberous sclerosis complex (TSC)-related refractory epilepsy.
Also backed by longevity-focused investors like Hevolution and Apollo Health Ventures, Berkeley, CA-based Aeovian is addressing a long-standing challenge in mTOR drug development. mTOR sits at the crossroads of nutrient sensing, cellular growth, stress response, proteostasis, metabolism and inflammation. In healthy cells, its two complexes, mTORC1 and mTORC2, operate in balance to maintain homeostasis. With aging and in specific genetic disorders, this balance breaks down, most often through chronic hyperactivation of mTORC1. While this dysregulation has been implicated in neurodegeneration, metabolic decline, immune dysfunction and other age-associated pathologies, therapeutic attempts to modulate the pathway have largely relied on drugs that inhibit both complexes. Those nonselective agents, including rapamycin analogs, have demonstrated biological activity but at the cost of tolerability issues that limit dosing, durability and long-term use – constraints that are especially problematic for chronic conditions linked to aging.
According to Aeovian, TSC offers a uniquely clear biological context to address this problem. Caused by certain gene mutations, the disease leads to unchecked mTORC1 activity, with epilepsy emerging as one of its most common and debilitating manifestations. AV078 was engineered to correct the pathological mTORC1 signaling while preserving the broader physiological functions of the pathway.
By selectively inhibiting mTORC1 and achieving penetration into the central nervous system, the compound is designed to directly address the hyperactive signaling driving neuronal network instability in TSC-related epilepsy, without triggering the downstream liabilities associated with mTORC2 inhibition. The ongoing Phase 2 study will test whether that selectivity translates into sustained seizure control with improved tolerability. For Aeovian, however, the implications extend well beyond epilepsy.
“While this program represents a precision medicine approach targeting a genetically defined rare disease, the underlying biology of mTORC1 implicates a broader range of more prevalent, age-related conditions,” said Aeovian CEO Dr Allison J Hulme. “Successful clinical validation of AV078 in TSC-refractory epilepsy is expected to derisk and validate Aeovian’s wholly owned, internally developed pipeline of selective mTORC1 inhibitors, enabling potential expansion into additional indications over time.”
From a translational standpoint, epilepsy serves as a measurable, mechanistically defined system in which to validate precise mTORC1 modulation in humans. Demonstrating that selective inhibition can safely restore cellular balance in the brain would provide critical clinical validation for a broader platform aimed at metabolic quality control. mTOR is not a disease-specific pathway; it is a central regulator of cellular resilience. Chronic dysregulation of mTORC1 is increasingly recognized as a contributor to the hallmarks of aging, including impaired proteostasis, heightened inflammatory tone, reduced stress adaptability and declining metabolic efficiency across tissues. A drug capable of correcting pathological mTORC1 activity without disrupting essential anabolic and survival signals would address one of the key barriers that has limited the translation of mTOR biology into viable therapeutics.
Aeovian is betting that precision control of mTORC1, rather than broad suppression of the pathway, may be necessary to unlock its therapeutic potential in chronic, age-related diseases. Successful clinical validation in a genetically defined population like TSC could reduce scientific and regulatory risk for expansion into more prevalent indications where mTORC1 overactivation emerges over time rather than from a single mutation.
While Aeovian’s near-term priority remains advancing AV078 through clinical development in epilepsy, the company is conducting additional preclinical work in age-related and chronic conditions characterized by inflammation, metabolic dysfunction and reduced cellular stress tolerance. These studies are designed to evaluate how selective mTORC1 inhibition affects core aging-associated processes across multiple tissues, laying the groundwork for future, healthspan-focused indications.
