Cerepeut | Targeting the Biology of Aging at its Core

The Opportunity

The Aging Process Can Be Altered

Aging drives most chronic disease and the biology behind it can be changed

Specific biological mechanisms drive aging

Mitochondrial dysfunction, inflammation, DNA damage

Lifespan is malleable

Caloric restriction and rapamycin extend lifespan across species

Human aging responds to intervention

Medicine delays cardiovascular, metabolic, and neurological decline

One target, many diseases

A fundamental mechanism of aging can change the course of multiple age-related conditions

The Problem

Aging is Driven by Interconnected Vicious Cycles

A network of self-reinforcing damage that progressively erodes cellular function

Mitochondrial dysfunction → energy failure → further mitochondrial decline

Oxidative stress → mitochondrial damage → more ROS

Tauopathy → misfolding → mitochondrial dysfunction → synaptic loss → more tauopathy

Impaired mitophagy → accumulation of damaged mitochondria → further impairment

Neuroinflammation → cytokine/ROS release → worsened tau & mitochondrial injury

NAD⁺ depletion → impaired repair & mitochondrial regulation → more damage

Calcium dysregulation → mitochondrial Ca²⁺ overload → ROS burst → cell death

Proteostasis failure → protein aggregates → increased cellular stress

The Biology

Mitochondria Sit at the Center of Aging

Energy failure and oxidative stress drive systemic decline

Mitochondrial Disorders and Aging Share the Same Core Biology

Aging and frailty are driven by progressive mitochondrial dysfunction
Energy failure and redox imbalance propagate systemic damage
Mitochondrial diseases are aging biology compressed in time

The Brain Is Where Aging Becomes Visible

Neurons are highly energy-dependent
Long-lived cells amplify damage over time
Cognitive and motor decline provide clear clinical signals

Our Science

A Single Mechanism Connecting Aging and Disease

Mitochondrial reverse electron transport (RET) drives oxidative stress and cellular dysfunction.

Cerepeut is built on a novel understanding of mitochondrial biology centered on reverse electron transport (RET). RET occurs in mitochondrial Complex I when electrons flow in reverse, generating reactive oxygen species (ROS) and altering the NAD⁺/NADH balance. Once viewed primarily as damaging, RET is now recognized as a central regulator of mitochondrial function, cellular homeostasis, and stress adaptation.

This biology has been extensively studied by our co-founders at Stanford University and UCSF. Recent work shows that RET is activated during aging, contributing to oxidative stress and redox imbalance, while its inhibition can restore cellular function and extend lifespan in model systems (Rimal et al., EMBO Reports, 2023; Rimal and Lu, Aging and Disease, 2026).

Additional studies link dysregulated RET to neurodegeneration, cancer, and other age-related diseases:

Diagram illustrating how mitochondrial reverse electron transport (RET) drives oxidative stress and mitochondrial damage in neurodegeneration

Lead Compound

CP-235: First-in-class Small Molecule Inhibitor of RET

Designed to Restore Mitochondria Balance

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Once-Daily Oral Therapy

Oral small molecule with strong bioavailability and a first-in-class mechanism of action

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Excellent Tissue Exposure

Demonstrated penetration into target tissues including the central nervous system

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Validated Across Models

Therapeutic activity confirmed across multiple experimental systems

Human Therapeutics

Advancing Human Therapeutics Against Neurodegeneration

Cerepeut's latest paper is out in Neuron, identifying a new driver of tauopathy and confirming what we've long suspected at Cerepeut: phosphorylated tau (pTau) enters mitochondria and triggers RET, forming a self-destructive feedback loop that generates more pTau. The study also shows that Cerepeut's lead drug candidate, CP-235, breaks the loop. Across fruit flies, mouse models, and human stem cell-derived neurons, it lowered pTau, rescued cognitive deficits, reduced brain atrophy, and calmed neuroinflammation. The study shows the same overactive RET signal shows up in human Alzheimer's brain tissue, not just animal models. Full Study: Tau-induced mitochondrial reverse electron transport drives neurodegeneration.

The brain is the earliest and clearest victim of aging — Neurodegeneration tightly tracks fundamental aging processes
Neurons are uniquely vulnerable — Long-lived, non-dividing, and highly energy-dependent cells amplify mitochondrial and redox failure
Multiple aging hallmarks converge — Mitochondrial dysfunction, oxidative stress, inflammation, and protein aggregation collapse into one phenotype
Clear clinical readouts — Cognition and motor function provide unambiguous, meaningful endpoints
Strong validation of fundamental mechanisms — Disease modification in the brain signals upstream control of aging biology