Organization Description
Aeovian is a San Francisco Bay Area-based research stage biopharmaceutical company aiming to discover, develop and commercialize therapeutics for the treatment of rare and age-related diseases. They are developing new small molecule mTOR inhibitors that are highly selective for the mTORC1 pathway.
Mechanistic target of rapamycin (mTOR) is an highly conserved kinase is the catalytic core of two protein assemblies: mTOR Complex 1 (mTORC1) and mTOR Complex 2 (mTORC2). Genetic disorders such as tuberous sclerosis complex (TSC) refractory epilepsy and focal cortical dysplasia (FCD) as well as biological aging result in excessive activation of mTORC1. Accordingly, inhibition of mTORC1 — either genetically or pharmacologically with drugs such as rapamycin/sirolimus — has been consistently reported to extend lifespan and slow or reverse age-related functional decline in lab rodents and other models, and there is some human evidence to support the translatability of these findings.
However, chronic treatment with conventional, non-selective mTOR inhibitors leads to off-target inhibition of mTORC2, which results in dose-limiting deleterious effects on metabolic health and possibly immune function. Aeovian proposes to address mTORC1-related disease and aging with novel mTOR inhibitors that do not lead to downstream mTORC2 inhibition.
In March 2024, Aeovian announced that it had secured a $50 million Series A financing extension led by a $20 million life science impact investment from Hevolution Foundation.
AV078, is a first-in-class CNS penetrant selective mTORC1 inhibitor being developed for the treatment of tuberous sclerosis complex (TSC) refractory epilepsy and is currently being evaluated in a Phase 1 trial. TSC is a rare genetic disorder caused by the hyperactive signaling of mTORC1.
AV078
AV078 is Aeovian’s first-in-class CNS-penetrant selective mTORC1 inhibitor, which is under development for the treatment of tuberous sclerosis complex (TSC) refractory epilepsy, a rare genetic disorder caused by excessive mTORC1 signaling. March 2024, Aeovian announced that it had dosed its first cohort of TSC epilepsy patients with AV078 in a Phase I trial. Its pipeline diagram indicates that AV078 is also in IND-enabling studies for focal cortical dysplasia.
AV805
AV805 is listed in Aeovian’s pipeline diagram as an additional CNS-penetrant selective mTORC1 inhibitor, evidently in early IND-enabling studies for the treatment of unspecified neurodegenerative diseases.
AV505
AV505 is listed in Aeovian’s pipeline diagram as a peripheral selective mTORC1 inhibitor, evidently in early IND-enabling studies for the treatment of unspecified metabolic diseases.
CD38 Inhibitors
Aeovian’s pipeline diagram indicates that it has both central and peripheral preclinical candidate inhibitors of CD38 in selection for unspecified indications. CD38 is a glycoprotein found on the surface of many immune cells, especially plasma B cells. CD38 can function either as a receptor or as an enzyme. As a receptor, CD38 can activate T-cells and modulate the activation of B-cells; as an enzyme, it can hydrolyze NAD+ into ADP ribose and cyclic ADPR. This NAD hydrolase activity is thought to contibute substantially to an age-related decline in NAD+ levels, although whether the latter is a meaningful problem in aging humans is uncertain.
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