Cortexyme, Inc. (now Quince Therapeutics, Inc.)

Pipeline (2)

• LHP588Small moleculeLysine-gingipain (Kgp) InhibitorLed by Lighthouse Pharmaceuticals, Inc.
  • Alzheimer's diseasePhase 2Recruiting
• Atuzaginstat (COR388)Small moleculeKgp Inhibitor
  • Alzheimer's diseaseDiscontinuedDiscontinued

Deals & partnerships

• LHP588Led by Lighthouse Pharmaceuticals, Inc.

• Apr 23, 2026FinancingLighthouse closes a $12M Series A led by Double Point VenturesLighthouse Pharmaceuticals closed a $12 million Series A financing led by Double Point Ventures with participation from new and existing investors, to advance LHP588 in Alzheimer's disease and expand the pipeline. Campbell Murray, M.D., a partner at Double Point Ventures, joined the board. The release reiterated that the SPRING trial is additionally supported by the $49.2M NIA grant and is currently enrolling participants across the United States.LHP588source ↗
• Aug 22, 2025FinancingNIA awards Lighthouse a $49.2M grant to fund the Phase 2 SPRING trial of LHP588The National Institute on Aging (NIH) awarded Lighthouse Pharmaceuticals $49.2 million under award R01AG088524 to support the Phase 2 SPRING trial of LHP588 in Alzheimer's disease patients with confirmed P. gingivalis infection. NIH RePORTER records the project as 'A Randomized, Double-Blind, Placebo-Controlled Study of LHP588 in Subjects with P. gingivalis-Positive Alzheimer's Disease', contact PI Michael J. Detke, M.D., Ph.D. (chief medical officer), project period 2025-08-15 to 2029-07-31, with $12,591,952 obligated in fiscal year 2025.LHP588source ↗
• Jan 27, 2023AcquisitionLighthouse Pharmaceuticals acquires Cortexyme's gingipain-inhibitor portfolio from Quince Therapeutics; COR588 becomes LHP588Quince Therapeutics (Nasdaq: QNCX, formerly Cortexyme, Inc.) sold its legacy small-molecule protease-inhibitor portfolio — COR588, COR388 (atuzaginstat), COR852 and COR803 — outright to Lighthouse Pharmaceuticals, Inc. under an asset purchase agreement consummated the same day. Lighthouse, co-founded by Casey Lynch, Cortexyme's former CEO, gained exclusive worldwide rights to develop, manufacture and commercialize the portfolio. Quince received 7.5% of Lighthouse's common stock with anti-dilution through the first $10M raised, up to $150M in regulatory and commercial milestone payments product-by-product, tiered royalties (high-single-digit to mid-teens on the two clinical-stage programs, low-single-digit on the preclinical ones) and a share of sublicense income; Quince also took an option, expiring 2023-06-30, on COR388 for animal-health indications. Quince described COR588 as 'a selective, oral small molecule inhibitor of lysine-gingipain that is Phase 2 ready'. The compound was renamed LHP588 under Lighthouse.LHP588source ↗
• Jan 27, 2023DivestitureQuince Therapeutics sells the legacy protease-inhibitor portfolio, including atuzaginstat, to Lighthouse PharmaceuticalsQuince Therapeutics (formerly Cortexyme) entered into and simultaneously consummated an Asset Purchase Agreement with Lighthouse Pharmaceuticals, Inc. for the sale of its legacy small-molecule protease-inhibitor portfolio for all uses and indications worldwide — COR388 (atuzaginstat), COR588, COR803 and COR852, plus drug substance, drug product, regulatory materials, intellectual property and related contracts. Consideration was common stock equal to 7.5% of Lighthouse's issued and outstanding shares, milestone payments of up to $150 million per product on regulatory approvals and net-sales thresholds, and royalties from high single-digit to mid-teens of annual net sales on the two clinical-stage programmes (low single-digit on the preclinical ones). Lighthouse was co-founded by former Cortexyme leadership and now develops the second-generation Kgp inhibitor LHP588 (COR588).Atuzaginstat (COR388)source ↗

Catalysts · 1 upcoming · 3 reported

• January 2029Anticipated

  LHP588forAlzheimer's diseaseRegistry results

  ClinicalTrials.gov estimated primary completion of the Phase 2 SPRING trial (NCT06847321) of LHP588 25 mg and 50 mg vs placebo in P. gingivalis-positive mild-to-moderate Alzheimer's disease: January 2029 (estimated study completion 2029-03-15).

  NCT06847321source ↗

Recently reported

• 2022-07-27met

  LHP588forAlzheimer's diseaseTopline data

  Cortexyme reported successful completion of the Phase 1 single- and multiple-ascending-dose study of COR588 (now LHP588): well tolerated from 25 mg to 200 mg with no serious adverse events, an 11-to-12-hour half-life supporting once-daily dosing, dose-proportional PK exceeding the exposure targeted for efficacy, and high CNS penetration confirmed after 10 days of dosing.

  source ↗

• 2021-11-11mixed

  Atuzaginstat (COR388)forAlzheimer's diseaseFull results

  Additional GAIN top-line results presented at CTAD 2021 (Boston, 9-12 November 2021): expanded P. gingivalis-infection subgroup analyses reinforcing the ~50% slowing of cognitive decline in infected participants across multiple pre-specified infection-related subgroups and analysis methods, plus periodontal sub-study and safety detail.

  source ↗

• 2021-10-26missed

  Atuzaginstat (COR388)forAlzheimer's diseaseTopline data

  GAIN Phase 2/3 topline MISSED both co-primary endpoints: atuzaginstat 40 mg and 80 mg BID showed no significant benefit on ADAS-Cog11 or ADCS-ADL at Week 48 in the overall 643-patient mild-to-moderate Alzheimer's cohort. A pre-specified P. gingivalis-saliva-positive subgroup (n=242) showed 57% slowing of cognitive decline at 80 mg BID (p=0.02), with no ADCS-ADL benefit and dose-related liver enzyme elevations up to 15%.

  source ↗

Recent activity

• Feb 17, 2025Phase changeLHP588·Alzheimer's diseasePhase 2Phase 2 advance: the SPRING trial (NCT06847321, LHP588-201) actual start date per ClinicalTrials.gov, announced by Lighthouse on 2025-02-26. The step before this — FDA's 'Study May Proceed' letter clearing the LHP588 IND on 2023-11-16 — is not represented as its own timeline row because the closed event vocabulary has no code for an IND clearance (see _comment, vocabulary gap `ind_cleared`); it is recorded in the program description.source ↗
• Aug 1, 2022Phase changeAtuzaginstat (COR388)·Alzheimer's diseaseDiscontinuedProgramme discontinued by the sponsor. On 2022-08-01 the renamed company (Quince Therapeutics, Nasdaq: QNCX) announced a strategic shift to a bone-targeting platform and disclosed 'the company's intent to out-license its legacy neuroscience and antiviral assets' — the first unambiguous, company-stated exit from the atuzaginstat programme. This is the discontinuation anchor; the earlier 2022-01-25 full clinical hold is logged separately because that announcement still described continued Alzheimer's development (of COR588). Cause chain: dose-dependent hepatotoxicity plus a missed co-primary endpoint. The compound was sold to Lighthouse Pharmaceuticals on 2023-01-27.source ↗
• Jul 27, 2022ReadoutLHP588·Alzheimer's diseasemetCortexyme reported successful completion of the Phase 1 single- and multiple-ascending-dose study of COR588 (now LHP588): well tolerated from 25 mg to 200 mg with no serious adverse events, an 11-to-12-hour half-life supporting once-daily dosing, dose-proportional PK exceeding the exposure targeted for efficacy, and high CNS penetration confirmed after 10 days of dosing.source ↗
• Apr 30, 2022Phase changeLHP588·Alzheimer's diseasePhase 1Phase 1 SAD/MAD completed (actual primary completion and study completion 2022-04-30 per ClinicalTrials.gov). Cortexyme announced SAD results on 2022-03-08 and the successful completion of the full study on 2022-07-27: well tolerated from 25 mg to 200 mg with no serious adverse events and no clinically significant vital-sign, laboratory, telemetry or ECG findings; dose-proportional PK with an 11-to-12-hour half-life consistent with once-daily dosing; high CNS penetration confirmed after 10 days of once-daily dosing in the MAD portion (50, 100, 200 mg).source ↗
• Jan 25, 2022Phase changeAtuzaginstat (COR388)·Alzheimer's diseasePhase 2/3FDA FULL clinical hold. Cortexyme received an FDA letter on 2022-01-25 placing a full clinical hold on atuzaginstat's IND 134303 (announced 2022-01-26), following the dose-dependent hepatotoxicity signal. The company immediately began a cost-reduction programme, said it would prioritise the next-generation gingipain inhibitor COR588 in Alzheimer's disease instead, and would 'explore strategic alternatives for its coronavirus program and non-Alzheimer's indications for COR388'. Recorded as 'suspended' rather than 'discontinued' because at this date the company had not yet stated it was abandoning the asset. The hold was never publicly lifted.source ↗
• Nov 11, 2021ReadoutAtuzaginstat (COR388)·Alzheimer's diseasemixedAdditional GAIN top-line results presented at CTAD 2021 (Boston, 9-12 November 2021): expanded P. gingivalis-infection subgroup analyses reinforcing the ~50% slowing of cognitive decline in infected participants across multiple pre-specified infection-related subgroups and analysis methods, plus periodontal sub-study and safety detail.source ↗
• Oct 26, 2021ReadoutAtuzaginstat (COR388)·Alzheimer's diseasemissedGAIN Phase 2/3 topline MISSED both co-primary endpoints: atuzaginstat 40 mg and 80 mg BID showed no significant benefit on ADAS-Cog11 or ADCS-ADL at Week 48 in the overall 643-patient mild-to-moderate Alzheimer's cohort. A pre-specified P. gingivalis-saliva-positive subgroup (n=242) showed 57% slowing of cognitive decline at 80 mg BID (p=0.02), with no ADCS-ADL benefit and dose-related liver enzyme elevations up to 15%.source ↗
• Aug 26, 2021Phase changeLHP588·Alzheimer's diseasePhase 1First-in-human Phase 1 randomized, double-blind, placebo-controlled single- and multiple-ascending-dose study of COR588 began at Nucleus Network in Melbourne, Australia, sponsored by Cortexyme, Inc. (64 healthy adult subjects, NCT04920903). COR588 was the compound later renamed LHP588 — Cortexyme became Quince Therapeutics on 2022-08-01 and sold the asset to Lighthouse Pharmaceuticals on 2023-01-27.source ↗
• Feb 15, 2021Phase changeAtuzaginstat (COR388)·Alzheimer's diseasePhase 2/3FDA PARTIAL clinical hold, imposed after its review of hepatic adverse events in the atuzaginstat trial. Scope was limited to the open-label extension: no new OLE enrolment and all enrolled OLE participants discontinued. The fully enrolled (N=643) double-blind, placebo-controlled phase was explicitly allowed to continue to its Q4 2021 topline, so the programme stays 'active' at this step rather than 'suspended'.source ↗
• Mar 28, 2019Phase changeAtuzaginstat (COR388)·Alzheimer's diseasePhase 2/3Pivotal Phase 2/3 GAIN trial (NCT03823404, COR388-010) started per ClinicalTrials.gov: randomised, quadruple-masked, placebo-controlled, 48 weeks of 40 mg or 80 mg BID in mild-to-moderate AD dementia, co-primary endpoints ADAS-Cog11 and ADCS-ADL, with an open-label extension and a periodontal-disease sub-study.source ↗
• Dec 11, 2017Phase changeAtuzaginstat (COR388)·Alzheimer's diseasePhase 1First-in-human. Phase 1 single ascending dose study COR388-001 (NCT03331900) started, 34 healthy adults, 5-250 mg oral capsules; completed 2018-04-02. Followed by the multiple ascending dose study COR388-002 (NCT03418688, started 2018-03-06, completed 2018-10-15) in 33 healthy older volunteers and patients with Alzheimer's disease. Status recorded as 'completed' because both Phase 1 studies did complete; no severe adverse events, drug-related TEAE rates 14% on COR388 vs 20% on placebo, and no dose-limiting toxicity.source ↗

Competitive landscape

Other companies developing against Cortexyme, Inc. (now Quince Therapeutics, Inc.)'s targets or indications.

• Intra-Cellular Therapies, Inc.1 compoundAlzheimer's disease
• Johnson & Johnson2 compoundsAlzheimer's disease
• Merck & Co., Inc.2 compoundsAlzheimer's disease