Restoring mitochondrial and lysosomal function in neurodegeneration

Reprogramming cells. Repairing neurons. Restoring lives.

Endurance Bio develops first-in-class oral small molecules designed to restore mitochondrial and lysosomal function through the PGC-1α–TFEB axis. Our lead programs, T-168 and T-621, target interconnected cellular systems that become dysfunctional in neurodegenerative, metabolic, muscle and age-related diseases - rather than a single downstream pathway. Our lead clinical program is Parkinson's disease.

T-168 and T-621 restore mitochondrial and lysosomal function in dopaminergic neurons, and restore dysfunctional and inflamed microglia to their normal, homeostatic state, reducing oxidative stress and inflammation while enhancing autophagy
T-168 has completed Phase 1 and is selected for the SLEIPNIR platform trial in Parkinson's disease, coordinated by Neuro-SysMed in Norway with funding from Cure Parkinson's, the Norwegian Parkinson's Research Fund and the Norwegian Parkinson's Association
T-621 is in preclinical development

Explore the science Request our deck

Clinical Phase 1 Completed

Completed in 77 healthy volunteers with excellent tolerability and PK results, no safety signals

Clinical Phase 2-ready

Placebo-controlled SLEIPNIR PD study, readout expected in 2028

First-in-class molecules

Our small molecules T-168 and T-621 have a unique Mechanism of Action to restore mitochondrial and lysosomal health simultaneously across different cell types

Pipeline-in-a-product

Broad indication opportunities across neurodegenerative, metabolic, aging and other diseases

Pipeline

Two first-in-class oral small molecules in development

A pipeline-in-a-product: T-168 delivers clinical proof-of-concept in Parkinson's disease, a stepping stone for indication expansion, while T-621 opens complementary indication positioning.

T-168

Phase 1 complete

Lead asset · first-in-class oral small molecule

Phase 1 successfully completed
Generally safe and well tolerated
Favorable PK supports once-daily oral dosing
Results published (Hannestad et al., Clin Transl Sci 2024)
Start of Phase 2 in Parkinson's disease expected in 4Q2026 (under publication)

T-621

Preclinical development

Second asset · active metabolite

In IND-enabling studies
Differentiated preclinical profile alongside T-168
Active metabolite of T-168 with a differentiated profile
Unique opportunity for indication positioning alongside T-168

A library of T-168 and T-621 analogs with composition of matter IP is available for exploration.

The problem

PGC-1α and TFEB are both impaired in neurodegenerative disease

The resulting biology spans mitochondrial, lysosomal and inflammatory pathways

PGC-1α is reduced in vulnerable brain regions in Parkinson's disease

CNS-specific PGC-1α transcripts are selectively reduced in the substantia nigra pars compacta, the dopaminergic region most affected in Parkinson's disease (Soyal et al., 2019). Reduced PGC-1α is a recognized contributor to mitochondrial failure and neuronal damage in the PD brain, with loss of PGC-1α function driving dopaminergic neurodegeneration in Parkinson's disease models (Shin et al., 2011).

PGC-1α deficit leads to dysfunctional microglial metabolism and neuroinflammation

Our scientific founders established that restoration of normal PGC-1α levels in inflamed and dysfunctional microglia induces a 'metabolic switch' from glycolysis to oxidative phosphorylation. This reduces the release of pro-inflammatory cytokines. Microglia are restored to their normal homeostatic state.

Nuclear TFEB translocation is impaired in patient brain

Nuclear TFEB, which is essential for lysosomal function, is reduced in dopaminergic neurons and in microglia of patients with Parkinson's disease. Reduced nuclear translocation is the result of α-synuclein pathology (Moors et al., 2024; Wang et al., 2026).

Because the two pathways are functionally linked, this dual loss compounds itself: cells lose the capacity to generate energy at the same time they lose the capacity to acidify lysosomes and clear damaged proteins such as α-synuclein, the pathological hallmark of Parkinson's disease.

The therapeutic gap

No approved therapy restores both the mitochondrial and lysosomal programs
Indirect approaches are weak and lack the necessary specificity
This biology is system-level, and hard to target through a single downstream node

The Endurance Bio solution and proposed mechanism

T-168 directly activates PGC-1α transcription
T-168 drives TFEB nuclear translocation
Acting upstream of most current and previously tested therapeutic approaches

Research is ongoing to further elucidate and confirm the proposed dual Mechanism of Action of T-168 across cell types and disease states.

Consistent biological activity across disease models

Across published and internal studies in Parkinson's disease, ALS and other neurodegeneration models, T-168 effects have been consistent and significant.

Increased survival
Enhanced motor function
Enhanced cognitive function
Reduced neuroinflammation
Replicated across several PD models (MPTP, SNCA*A53T), KA, and SOD1/TDP-43 ALS models
Benefits disappear when PGC-1α is deleted in microglia

Independently published work in Retinitis Pigmentosa, Cognitive Impairment, Fragile X syndrome and PTSD converges on the same PGC-1α mechanism. Our scientific slide deck and publications deck are available upon request — get in touch.

T-168 enhanced mobility and wheel-running in a Parkinson's disease mouse model

Control
T-168

Immobility duration (% reduction compared to healthy animals — lower scores are better)

Wheel-running activity (% reduction compared to healthy animals — lower scores are better)

SNCA*A53T model (a-syn), with and without PGC-1a in microglia.

Source: internal data / reports

T-168 reduced frailty in aged wildtype mice

Young mice — control (dashed line)
Young mice — T-168 (dashed line)
Old mice — control
Old mice — T-168

Clinical frailty index (lower scores are better)

Week

Mechanism of action

T-168 upregulates PGC-1α to restore cellular health

T-168 increases PGC-1α expression and drives TFEB nuclear translocation, restoring interconnected mitochondrial and lysosomal pathways.

In dopaminergic neurons

Mitochondrial biogenesis: NRF1, TFAM and mitochondrial mass increase, restoring ATP production
Mitophagy restored via PINK1/Parkin-mediated clearance of damaged mitochondria
MFN1-driven mitochondrial fusion
Lysosomal function & autophagy: TFEB nuclear translocation and restored acidification via V-ATPase assembly

In microglia

Metabolic switch from glycolysis toward oxidative phosphorylation
Reduced inflammatory cytokine release (TNF, IL-6)
More homeostatic phagocytosis — effect disappears when PGC-1α is deleted specifically in microglia
Enhanced autophagy and clearance of damaged proteins

Clinical

SLEIPNIR: a biomarker-driven platform trial in Parkinson's disease

SLEIPNIR is sponsored and coordinated by Neuro-SysMed in Norway, with funding support from Cure Parkinson's, the Research Council of Norway, the Western Norway Regional Health Authority and the Norwegian Parkinson's Association. T-168 has been selected as one of the first compounds on the platform. The planned Phase 2 study is placebo-controlled, enrolling 60 patients with a treatment duration of 3 months. Biomarker and clinical proof-of-concept data is expected in 2028.

Biomarkers

Brain energetics and glucose metabolism (PET and MRI)
Markers of mitochondrial and lysosomal health (CSF and plasma)
Markers of disease and neuronal injury (α-syn, NfL; CSF and plasma)
Markers of inflammation (CSF and plasma)
CNS penetration

Clinical assessment

MDS-UPDRS
Grip strength (handheld dynamometer)
Axivity AX6 wearable activity tracking
B-SIT smell test

The biomarker-rich design is intended to establish the relationship between drug exposure, CNS biological activity and clinical outcomes directly in Parkinson's disease patients.

Trial partnersNeuro-SysMedCure Parkinson'sThe Norwegian Research CouncilNorges Parkinsonforbund

Indication expansion

One upstream mechanism, a broad therapeutic opportunity

Because PGC-1α and TFEB sit upstream of a shared cellular maintenance program, and because the same mechanism has shown effect across multiple independent disease models, the platform's relevance extends beyond Parkinson's disease. Mitochondrial dysfunction and loss of proteostasis are both recognized among the hallmarks of aging, with mitochondrial decline increasingly viewed as a central driver of the other hallmarks (López-Otín et al., 2023). By simultaneously restoring mitochondrial and lysosomal function, T-168 impacts several of these hallmarks at once, rather than acting on a single isolated pathway.

Diagram of the hallmarks of aging, with mitochondrial dysfunction among the antagonistic hallmarks — Hallmarks of Aging. Adapted from López-Otín, C., et al. (2023). https://doi.org/10.1016/j.cell.2022.11.001 (opens in a new tab)

Indication opportunities in neurodegeneration

Indication opportunities include orphan and non-orphan diseases including:

Orphan: Amyotrophic Lateral Sclerosis (ALS), Frontotemporal Dementia (FTD), Friedreich's Ataxia (FA), Huntington's Disease (HD)

Prevalent: Alzheimer's Disease (AD), Parkinson's Disease (PD)

Emerging opportunities: aging, frailty, metabolic and muscle diseases

In aged wild-type mice, T-168 produced a 50% lower frailty score, 28% less fat mass with no loss of muscle mass, 25% greater grip strength and roughly 50% greater treadmill endurance versus vehicle-treated aged controls.

Two cages of aged mice photographed after three months of treatment: the treated group is visibly more active with fuller fur — Photos taken after 3 months of treatment.

Team

Experienced team with a proven track record in drug development

TEAM

Frederic Godderis, MS
Founder · CEO · Director
Enchi Liu, PhD
Co-founder · Chief Development Officer
Andrew Lam, MS
Co-founder · Chief Technology Officer
Subhasis Roy, MBA
CFO - CBO
Clarence R. Hurt, PhD
Discovery Research / Medicinal Chemistry

Board of Directors

Taro Inaba, BE, MBA
Managing Partner, Remiges Ventures
Jackson Streeter, MD
Florida Opportunity Fund / Director, UF Innovate Ventures / Partner, DeepWork Capital
Frederic Godderis, MS
Founder · CEO · Director
Sanjay Kakkar, MD, MPH
Founder · Director · CEO, Tensive SRL · Former Chairman, Tranquis Therapeutics

Advisors

Edgar Engleman, MD, PhD
Scientific founder · Professor of Pathology and Medicine, Stanford University · Founder, Vivo Capital
Charalampos Tzoulis, MD, PhD
Advisor · Professor of Neurology & Neurogenetics, University of Bergen, Norway

Partners

Investors and collaborations

Endurance Bio is backed by specialist life-science investors and advances its clinical program thanks to the support of leading Parkinson's disease research organizations.

Managed by DeepWork Capital logo

Publications

Selected key literature

(In certain publications, T-168 is also referred to as TQS-168 or ZLN005)