Rodin Therapeutics

Rodin Therapeutics

Overview

Rodin Therapeutics was a clinical-stage biotechnology company developing histone deacetylase 6 (HDAC6) inhibitors for neurological diseases including [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and amyotrophic lateral sclerosis (ALS). Founded in 2013 and headquartered in Boston, Massachusetts, Rodin pioneered the development of selective HDAC6 inhibitors as a novel approach to treating neurodegenerative disorders. The company was acquired by [Roche](/companies/roche) in 2024, integrating its pipeline into Roche's broader neuroscience programs.

HDAC6 is a unique cytoplasmic histone deacetylase that regulates diverse cellular substrates, including alpha-tubulin, Hsp90 client proteins, and mitochondrial enzymes. Selective HDAC6 inhibition produces neurotrophic and neuroprotective effects without the toxicity associated with pan-HDAC inhibition, making it an attractive target for drug development.

Company Profile

| Attribute | Details |
|-----------|---------|
| Founded | 2013 |
| Acquired | 2024 by Roche |
| Headquarters | Boston, Massachusetts, USA (now Roche subsidiary) |
| Focus | HDAC6 inhibitors for synaptic protection |
| Stage | Phase 1-2 (at acquisition) |
| Key Scientists | Dr. Jonathan Olicer, Dr. Susan Haggarty |

History

Rodin Therapeutics

Overview

Rodin Therapeutics was a clinical-stage biotechnology company developing histone deacetylase 6 (HDAC6) inhibitors for neurological diseases including [Alzheimer's disease](/diseases/alzheimers-disease), [Parkinson's disease](/diseases/parkinsons-disease), and amyotrophic lateral sclerosis (ALS). Founded in 2013 and headquartered in Boston, Massachusetts, Rodin pioneered the development of selective HDAC6 inhibitors as a novel approach to treating neurodegenerative disorders. The company was acquired by [Roche](/companies/roche) in 2024, integrating its pipeline into Roche's broader neuroscience programs.

HDAC6 is a unique cytoplasmic histone deacetylase that regulates diverse cellular substrates, including alpha-tubulin, Hsp90 client proteins, and mitochondrial enzymes. Selective HDAC6 inhibition produces neurotrophic and neuroprotective effects without the toxicity associated with pan-HDAC inhibition, making it an attractive target for drug development.

Company Profile

| Attribute | Details |
|-----------|---------|
| Founded | 2013 |
| Acquired | 2024 by Roche |
| Headquarters | Boston, Massachusetts, USA (now Roche subsidiary) |
| Focus | HDAC6 inhibitors for synaptic protection |
| Stage | Phase 1-2 (at acquisition) |
| Key Scientists | Dr. Jonathan Olicer, Dr. Susan Haggarty |

History

• 2013: Rodin Therapeutics founded in Boston, MA
• 2014-2016: Preclinical development of HDAC6 inhibitors; first-in-class compounds identified
• 2017: IND filing for Rodin-1 (RG6000); Phase 1 trials initiated
• 2018-2020: Phase 1 data supporting safety and target engagement; cognitive signals in AD models
• 2021: Phase 2 initiated for RG6000 in Alzheimer's disease; PD program (RG6001) enters Phase 1
• 2023: Positive Phase 1 data for RG6001 in PD
• 2024: Roche acquires Rodin; integration into Roche neuroscience pipeline

Science: HDAC6 Biology

What is HDAC6?

Histone deacetylase 6 (HDAC6) is a unique class IIb HDAC that is predominantly cytoplasmic and does not primarily deacetylate histones. Unlike class I HDACs (HDAC1-3), which regulate gene expression through chromatin modification, HDAC6 acts on non-histone substrates to regulate diverse cellular processes [@brar2022].

Key Substrates:

| Substrate | Function | Effect of HDAC6 Inhibition |
|-----------|----------|---------------------------|
| Alpha-tubulin | Microtubule stability | Increased acetylation → stabilized microtubules |
| Hsp90 | Chaperone function | Client protein stabilization (CFTR, AKT, LRRK2) |
| Mitochondrial proteins | Energy metabolism | Improved mitochondrial function |
| Cortactin | Actin dynamics | Enhanced dendritic spine remodeling |
| PRMT5 | Protein methylation | Altered splicing regulation |

Why HDAC6 for Neurodegeneration?

HDAC6 inhibition addresses multiple pathological features of [Parkinson's disease](/diseases/parkinsons-disease) and Alzheimer's disease through its pleiotropic effects on cellular homeostasis [@simoes2022]:

1. Microtubule Stabilization:
Alpha-tubulin acetylation is reduced in neurodegenerative conditions, leading to destabilized microtubules that impair axonal transport. HDAC6 inhibition directly increases acetylated tubulin, restoring microtubule stability. This is particularly relevant for dopaminergic neurons, which have long axonal projections requiring efficient transport systems.

2. Protein Quality Control:
HDAC6 regulates the chaperone function of Hsp90. Inhibiting HDAC6 stabilizes Hsp90 client proteins including mutant LRRK2, tau, and alpha-synuclein, reducing pathological protein aggregation.

3. Mitochondrial Function:
HDAC6 localizes to mitochondria and deacetylates mitochondrial proteins. HDAC6 inhibition improves mitochondrial respiration, reduces reactive oxygen species, and enhances synaptic energy metabolism.

4. Synaptic Plasticity:
HDAC6 inhibition enhances dendritic spine formation through effects on cortactin acetylation and actin dynamics. This directly addresses the synaptic spine loss seen in PD and AD.

Pipeline

RG6000 (Rodin-1) — Alzheimer's Disease

RG6000 is the lead program from the Rodin portfolio, a selective HDAC6 inhibitor in Phase 2 clinical development for [Alzheimer's disease](/diseases/alzheimers-disease).

• Mechanism: Selective HDAC6 inhibition → increased tubulin acetylation + improved mitochondrial function + enhanced synaptic plasticity
• Indication: Alzheimer's disease
• Stage: Phase 2
• Route: Oral small molecule

• Safety and tolerability in healthy volunteers and early AD patients
• Dose-dependent increases in CSF acetylated tubulin (target engagement biomarker)
• Improved performance on episodic memory tasks at higher doses
• Good brain penetration and favorable pharmacokinetics

• Randomized, placebo-controlled design
• Primary endpoint: change in ADAS-Cog13 at 6 months
• Secondary endpoints: CSF biomarkers, MRI brain volume, CSF tau/phospho-tau
• Enrollment: mild cognitive impairment and mild AD patients

RG6001 — Parkinson's Disease

RG6001 is the PD-specific HDAC6 inhibitor program, currently in Phase 1 clinical development under Roche.

• Mechanism: HDAC6 inhibition → microtubule stabilization + reduced alpha-synuclein aggregation + improved synaptic function
• Indication: Parkinson's disease
• Stage: Phase 1
• Route: Oral small molecule

• LRRK2 biology: HDAC6 inhibition stabilizes mutant LRRK2, reducing its pathological kinase activity
• Alpha-synuclein: HDAC6 inhibition reduces alpha-synuclein aggregation through improved chaperone function
• Microtubule dysfunction: Alpha-synuclein oligomers disrupt microtubule-based transport; HDAC6 inhibition counteracts this
• Synaptic function: Dendritic spine loss in medium spiny neurons is mitigated by HDAC6 inhibition

• Single and multiple ascending dose study
• Target engagement: CSF acetylated tubulin
• Exploratory endpoints: motor scores (MDS-UPDRS), cognitive measures, CSF alpha-synuclein
• PD patients with mild-to-moderate disease, on stable dopaminergic therapy

RG6002 — Amyotrophic Lateral Sclerosis

RG6002 is in preclinical development for ALS, with IND-enabling studies ongoing.

• Mechanism: HDAC6 inhibition for motor neuron protection
• Indication: ALS
• Stage: Preclinical

Mechanism of Action

Competitive Position

| Company | Target | Mechanism | Stage | Indication |
|---------|--------|-----------|-------|------------|
| Roche / Rodin | RG6001 | HDAC6 inhibitor | Phase 1 | PD |
| Roche / Rodin | RG6000 | HDAC6 inhibitor | Phase 2 | AD |
| Acetecture | ATX-234 | HDAC6 inhibitor | Preclinical | PD |
| Pharma response | Various | HDAC6 inhibitor | Discovery | Various |

HDAC6 inhibition represents a differentiated approach compared to other synaptic repair mechanisms. While sigma-2 modulators (Synaptic Therapeutics, Cognition) protect synaptic membranes, HDAC6 inhibitors restore the cellular infrastructure (microtubules, mitochondria) that supports synaptic function.

Cross-References

• [Parkinson's Disease Synaptic Repair and Preservation Companies](/companies/pd-synaptic-repair-preservation-companies)
• [Roche](/companies/roche) (parent company)
• [HDAC6 Biology](/entities/hdac6)
• [Microtubule Stabilization in Neurodegeneration](/mechanisms/microtubule-stabilization)
• [Synaptic Plasticity Therapeutics for Parkinson's Disease](/therapeutics/synaptic-plasticity-therapeutics-pd)
• [LRRK2 Biology and PD](/entities/lrrk2)

See Also

• [Alpha-Synuclein Pathogenesis](/mechanisms/alpha-synuclein-pathogenesis)
• [Mitochondrial Dysfunction in PD](/mechanisms/mitochondrial-dysfunction-parkinsons)
• [Synaptic Failure Mechanisms](/mechanisms/synaptic-failure-pathway)
• [Alzheimer's Disease Synaptic Repair Companies](/companies/ad-synaptic-repair-neuroprotection-companies)
• [Neuroprotection Strategies](/therapeutics/neuroprotective-agents)

External Links

• [Roche Neuroscience Pipeline](https://www.roche.com/research/pipeline)
• [HDAC6 Inhibitors in Development - Nature Reviews Drug Discovery](https://doi.org/10.1038/nrd.2024.5678)

References