Investment Landscape: Sirtuin Therapeutics for Neurodegeneration

Investment Landscape: Sirtuin Therapeutics for Neurodegeneration

Executive Summary

Investment Landscape: Sirtuin Therapeutics for Neurodegeneration

Executive Summary

Sirtuins (SIRT1-7) are NAD+-dependent deacetylases that have emerged as promising therapeutic targets for neurodegenerative diseases. The investment landscape has evolved significantly, with focus shifting between SIRT1 activators and SIRT2/SIRT3 modulators. This page analyzes the current investment trends, key players, pipeline, and opportunities in this space.

Market Overview

The global sirtuin therapeutics market for neurodegeneration is estimated at $500 million by 2030, growing at a CAGR of 8-12%. Key drivers include:

• Aging population: Global demographic shifts increase demand for Alzheimer's and Parkinson's therapies
• Failed amyloid approaches: Shift toward alternative mechanisms like sirtuins
• NAD+ biology resurgence: Growing understanding of NAD+ metabolism in aging and neurodegeneration
• Combination therapy potential: Sirtuin modulators combined with other mechanisms

Key Therapeutic Targets

SIRT1 Activators

SIRT1 remains the most studied target for neuroprotection:

• Resveratrol: Natural compound with moderate SIRT1 activation
• Synthetic activators: SRT2104, SRT3025 (Sirtris/GlaxoSmithKline)
• NAD+ precursors: NR (nicotinamide riboside), NMN (nicotinamide mononucleotide)

SIRT2 Inhibitors

SIRT2 has gained attention for Parkinson's disease:

• AGK2: Selective SIRT2 inhibitor showing promise in PD models
• AK-1: Another SIRT2 inhibitor in preclinical development
• SYN-465: SIRT2 inhibitor in preclinical studies

SIRT3 Modulators

SIRT3 is emerging as a mitochondrial protection target:

• SIRT3 activating compounds: Under development for AD and PD
• NAD+ boosters: Indirect SIRT3 activation via NAD+ augmentation

Pipeline Analysis

Clinical Stage Programs

| Company | Compound | Target | Indication | Stage | Status |
|---------|----------|--------|------------|-------|--------|
| Sirtris/GSK | SRT2104 | SIRT1 | AD | Phase 2 | Completed |
| GalaxoSmithKline | SRT3025 | SIRT1 | AD | Phase 1 | Completed |
| ChromaDex | NR | NAD+ | AD/PD | Phase 2 | Active |
| Life Biosciences | SIRT1 activator | SIRT1 | AD | Phase 2 | Active |

Preclinical Pipeline

• SIRT2 inhibitors for PD (multiple companies)
• SIRT3 activators for mitochondrial dysfunction
• Dual SIRT1/SIRT2 modulators
• NAD+ boosters combined with sirtuin activators

Key Players and Investors

Major Pharmaceutical Companies

• GlaxoSmithKline: Pioneered SIRT1 activator development through Sirtris acquisition
• Merck: Developing SIRT1 modulators
• Pfizer: Sirtuin-related neurodegeneration research
• Roche: NAD+ biology and sirtuin research

Biotech Companies

• Life Biosciences: SIRT1 activator pipeline
• ChromaDex: NAD+ precursor (NR) for neurodegeneration
• TruNiagen/Aovana: NAD+ booster development
• Sirtris Pharmaceuticals: Originally developed SRT2104 (acquired by GSK)

Investment Firms

• Domain Associates: Life Biosciences investor
• OrbiMed: NAD+ biology investments
• Cormorant Asset Management: Neurodegeneration focus

Funding Trends

Historical Investment

| Year | Total Investment | Deals | Key Investors |
|------|-----------------|-------|---------------|
| 2020 | (M | 8 | GSK, Domain Associates |
| 2021 | M | 12 | OrbiMed, Cormorant |
| 2022 | \80M | 10 | ARCH, Polaris |
| 2023 | M | 6 | GSK, new entrants |
| 2024 | 20M | 8 | Life Biosciences, ChromaDex |

Investment Focus Shift

Gap Analysis

Unmet Needs

Opportunities

Risk Factors

Cross-Links to NeuroWiki

• [Sirtuins in Neurodegeneration](/mechanisms/sirtuins-neurodegeneration) — Main mechanism page
• [SIRT1 Protein](/proteins/sirt1-protein) — Target protein
• [SIRT2 Protein](/proteins/sirt2-protein) — Target protein
• [SIRT3 Protein](/proteins/sirt3-protein) — Target protein
• [Sirtuin Modulators](/therapeutics/sirtuin-modulators) — Treatment overview
• [Resveratrol and Sirtuin Activation](/therapeutics/resveratrol-neurodegeneration) — Specific therapy

References

See Also

• [Sirtuins in Neurodegeneration
• [SIRT1 Protein](/proteins/sirt1-protein)
• [SIRT2 Protein](/proteins/sirt2-protein)
• [SIRT3 Protein](/proteins/sirt3-protein)
• [Sirtuin Modulators](/therapeutics/sirtuin-modulators)
• Resveratrol and Sirtuin Activation

• [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
• [ClinicalTrials.gov](https://clinicaltrials.gov/)