Overview
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companies_cortexyme["Cortexyme / Quince Therapeutics"]
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companies_cortexyme_0["Company Overview"]
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companies_cortexyme_1["Company History"]
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companies_cortexyme_2["Key Milestones"]
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companies_cortexyme_3["Technology Platform"]
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companies_cortexyme_4["Gingipain Inhibitor Platform"]
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companies_cortexyme_5["Why Target Bacteria"]
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...Overview
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Cortexyme, Inc. (NASDAQ: CRXT) is a clinical-stage biotechnology company that was rebranded to Quince Therapeutics in 2024 following a strategic acquisition. The company focuses on developing disease-modifying therapies for Alzheimer's disease and other neurodegenerative conditions through a novel approach targeting bacterial pathogens, particularly Porphyromonas gingivalis[@quince].
Company Overview
| Attribute | Details |
|-----------|---------|
| Ticker | NASDAQ: CRXT |
| Founded | 2012 (as Cortexyme) |
| Headquarters | San Francisco, California, USA |
| CEO | Casey Lynch |
| Former Name | Cortexyme, Inc. |
| Current Name | Quince Therapeutics (2024) |
| Market Cap | ~$30-50M (2024) |
Company History
Cortexyme was founded in 2012 by Casey Lynch and Dr. Stephen Dominy, who had been researching the connection between chronic periodontal disease and Alzheimer's disease. The company's approach was groundbreaking in proposing that bacterial pathogens could be a causative factor in neurodegenerative disease.
In 2024, the company rebranded to Quince Therapeutics after acquiring a pipeline of experimental therapeutics.
Key Milestones
- 2012: Company founded in San Francisco
- 2018: Raised 5M Series B funding
- 2019: Announced positive Phase 1b data for COR388
- 2020: GAIN Trial (Phase 2/3) initiated for COR388 in Alzheimer's
- 2021: Completed 0M Series C; IPO on NASDAQ
- 2024: Rebranded to Quince Therapeutics
Cortexyme/Quince's therapeutic approach centers on gingipain inhibitors — small molecule drugs that target and inhibit the toxic gingipain enzymes produced by Porphyromonas gingivalis:
R gingipains (Rgp): Arginine-specific gingipains
K gingipains (Kgp): Lysine-specific gingipainsThese enzymes are critical for P. gingivalis survival and pathogenicity, and have been shown to:
- Degrade [tau protein](/proteins/tau) and neuronal proteins[@porphyromonas]
- Activate pro-inflammatory cascades
- Disrupt [blood-brain barrier](/entities/blood-brain-barrier) integrity
- Cause direct neuronal death
Why Target Bacteria?
The bacterial hypothesis of Alzheimer's represents a paradigm shift:
- Epidemiological link: Chronic periodontitis associated with 1.7x increased AD risk
- Direct detection: P. gingivalis DNA found in AD brain tissue
- Gingipain antigens: Detected in AD cerebrospinal fluid and brain
- Animal models: P. gingivalis infection causes tau pathology and cognitive decline
- Treatment potential: Gingipain inhibitors reduce pathology in mouse models
Clinical Pipeline
COR388 (Gingipain Inhibitor) — Alzheimer's Disease
COR388 (later renamed in Quince pipeline) is the lead program targeting P. gingivalis gingipains.
| Attribute | Details |
|-----------|---------|
| Name | COR388 (Atuzabtagene autoleucel - no, that's different) |
| Target | Rgp and Kgp gingipains |
| Mechanism | Small molecule gingipain inhibitor |
| Indication | Alzheimer's disease |
| Phase | Phase 2/3 (GAIN Trial) |
| Route | Oral |
GAIN Trial
The GAIN (GingipAIN) trial is a pivotal Phase 2/3 clinical trial:
- Design: Randomized, double-blind, placebo-controlled
- Enrollment: ~600 patients with mild-to-moderate Alzheimer's
- Primary Endpoint: Change in ADAS-Cog11 at 12 months
- Secondary Endpoints:
- CSF gingipain activity biomarkers
- Inflammatory markers (IL-6, TNFα)
- Clinical dementia rating (CDR)
- Status: Active, completing enrollment
Phase 1b Results
Earlier Phase 1b studies showed[@gingipain]:
- Dose-dependent target engagement
- Reduction in gingipain activity in CSF
- Acceptable safety profile at all doses
- Preliminary cognitive stabilization signals
COR395 — Parkinson's Disease
Preclinical program targeting P. gingivalis in Parkinson's disease:
| Attribute | Details |
|-----------|---------|
| Target | Gingipains |
| Indication | Parkinson's disease |
| Status | Preclinical |
Rationale: P. gingivalis may contribute to [alpha-synuclein](/proteins/alpha-synuclein) aggregation and neuroinflammation in PD.
Scientific Foundation
The P. gingivalis-Alzheimer's Hypothesis
Dr. Stephen Dominy's research established the scientific foundation for this approach[@porphyromonas]:
Brain Invasion: P. gingivalis can enter the brain via:
- Olfactory tract (direct nose-to-brain pathway)
- Infected monocytes (Trojan horse mechanism)
- Compromised blood-brain barrier
Gingipain Toxicity: Once in the brain, gingipains:
- Degrade tau (leading to neurofibrillary tangles)
- Cleave [amyloid precursor protein](/entities/app-protein) (increasing [Aβ](/proteins/amyloid-beta) production)
- Cause neuronal death
- Trigger chronic inflammation
Evidence in Human Brain:
- P. gingivalis DNA found in 90% of AD brains vs. controls
- Gingipain antigens colocalize with tau pathology
- Gum infection correlates with cognitive decline
Key Publications
- Dominy et al. (2019). Porphyromonas gingivalis in Alzheimer disease. Journal of Alzheimer's Disease[@porphyromonas]
- Ilievski et al. (2018). Chronic oral application of P. gingivalis causes tau pathology. Journal of Alzheimer's Disease
- Chen et al. (2017). P. gingivalis lipopolysaccharide in brain triggers inflammation. Journal of Neuroinflammation
- IPO: 2021 at 6/share
- 2024 Range: /bin/bash.30-1.50/share
- Market Cap: ~0-50M
Funding History
| Round | Year | Amount |
|-------|------|--------|
| Series A | 2016 | 5M |
| Series B | 2018 | 5M |
| Series C | 2021 | 0M |
| IPO | 2021 | 5M |
Leadership
- Casey Lynch — CEO, Co-founder
- Stephen Dominy, MD — Chief Scientific Officer, Co-founder
- Michael J. Fox Foundation — Key research supporter
Competitive Landscape
Anti-Amyloid vs. Anti-Bacterial Approaches
| Approach | Examples | Mechanism |
|----------|----------|-----------|
| Anti-amyloid | Leqembi, [Donanemab](/entities/donanemab) | Remove Aβ plaques |
| Anti-tau | Anti-tau antibodies | Block tau pathology |
| Anti-inflammatory | XPro1595 | Reduce neuroinflammation |
| Anti-bacterial | COR388 | Remove bacterial trigger |
Controversies and Challenges
The bacterial hypothesis has faced skepticism:
- Causality vs. Correlation: Is P. gingivalis cause or consequence?
- Antibiotic Studies: Minocycline trials failed in AD
- Replication: Need more independent confirmations
- GAIN Trial Results: Pending (as of 2024)
Cross-References
Related Disease Pages
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Tau Pathology](/mechanisms/tau-pathology)
- [Amyloid Cascade Hypothesis](/mechanisms/amyloid-cascade)
Related Mechanism Pages
- [Neuroinflammation](/mechanisms/neuroinflammation)
- [Microbiome-Gut-Brain Axis](/mechanisms/gut-brain-axis-tauopathy)
- [Periodontitis-Alzheimer's Link](/mechanisms/periodontitis-alzheimers-link)
Related Company Pages
- [Biogen](/companies/biogen) — Leqembi developer
- [Eli Lilly](/companies/eli-lilly) — Donanemab developer
- [INmune Bio](/companies/inmune-bio) — Neuroinflammation approach
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
References
Unknown, Quince Therapeutics Website (n.d.)
[Unknown, Porphyromonas gingivalis in Alzheimer Disease (n.d.)](https://pubmed.ncbi.nlm.nih.gov/30570076/)
[Unknown, Gingipain Inhibitor Treatment for Alzheimer's Disease (n.d.)](https://pubmed.ncbi.nlm.nih.gov/31326549/)
Unknown, GAIN Trial Design (n.d.)