atuzaginstat (COR388) / Lighthouse Pharma - LARVOL DELTA

Porphyromonas gingivalis, neuroinflammation and Alzheimer's disease. (PubMed, Niger J Physiol Sci) - "In addition, some treatment methods could modulate the adverse effects of P. gingivalis like probiotic dietary supplements, maintaining personal hygiene, as well as gingipain inhibitors which modulate cytokines through blocked Aβ production, ApoE proteolysis, and reduced neuroinflammation. In addition, therapeutic compounds like COR388 and COR286, as gingipain inhibitors, prevent P. gingivalis colonization in the brain and have a beneficial action in some conditions like aspiration pneumonia, low birth rate, rheumatoid arthritis, PerioD and AD."

Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Cognitive Disorders • Dementia • Dental Disorders • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Arthritis • Inflammatory Bowel Disease • Metabolic Disorders • Movement Disorders • Obesity • Oncology • Parkinson's Disease • Periodontitis • Pneumonia • Respiratory Diseases • Rheumatoid Arthritis • Rheumatology • Targeted Protein Degradation • APOE

Phase 1 SAD/MAD data and Phase 2 study design for LHP588, a second-generation gingipain inhibitor for the treatment of P. gingivalis-positive Alzheimer's dementia (CTAD 2023) - P1, P2/3 | "LHP588 was well-tolerated in healthy volunteers without evidence of hepatic safety signals to date, and its PK profile was supportive of once daily dosing. The Phase 2 trial of LHP588 will be similar in design to the prior atuzaginstat study but will be restricted to subjects with Pg+ saliva. gingivalis, Alzheimer’s."

P1 data • P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Developmental Disorders • Infectious Disease • Inflammation

The gingipain inhibitor atuzaginstat and results of the GAIN trial (AAIC 2023) - "Since the patients most likely to benefit from the results of the clinical trials underway are those with mild-to-moderate AD, more studies are being planned. Atuzaginstat can address the ongoing need for treatment for most patients for whom anti-amyloids are not suitable."

Alzheimer's Disease • Dental Disorders • Hepatology • Infectious Disease • Periodontitis

Phase 2 Study Design and New Data from the Phase 1 SAD/MAD Trial of LHP588, A Second-Generation Gingipain Inhibitor for the Treatment of P. Gingivalis - Positive Alzheimer Dementia (AAIC 2023) - "Conclusion : LHP588 was well-tolerated in healthy volunteers without evidence of hepatic safety signals to date, and its PK profile was supportive of once daily dosing. The Phase 2 trial of LHP588 proposed to start in late 2023 will be similar in design to the prior atuzaginstat study but will be restricted to subjects with Pg + saliva."

New P1 trial • P1 data • P2 data • Alzheimer's Disease • CNS Disorders • Dementia • Infectious Disease • Inflammation • Targeted Protein Degradation

Phase 2 Study Design and New Data from the Phase 1 SAD/MAD Trial of LHP88, a Second-Generation Gingipain Inhibitor for the Treatment of P. Gingivalis-Associated Dementia (ASCP 2023) - "LHP588 was well tolerated in healthy volunteers without evidence of hepatic safety signals to date, and its PK profile was supportive of once daily dosing, with 10x lower liver metabolite levels. Chronic toxicology and rodent metabolite studies are also supportive of safety and progression to Phase 2. Clinical results with the first generation gingipain inhibitor atuzaginstat informed the new study design for precision enrollment and efficacious exposures."

New P1 trial • P1 data • P2 data • Alzheimer's Disease • CNS Disorders • Dementia

Phase 2 Study Design and New Data from the Phase 1 SAD/MAD Trial of LHP88, a Second-Generation Gingipain Inhibitor for the Treatment of P. Gingivalis-Associated Dementia (ASCP 2023) - "LHP588 was well tolerated in healthy volunteers without evidence of hepatic safety signals to date, and its PK profile was supportive of once daily dosing, with 10x lower liver metabolite levels. Chronic toxicology and rodent metabolite studies are also supportive of safety and progression to Phase 2. Clinical results with the first generation gingipain inhibitor atuzaginstat informed the new study design for precision enrollment and efficacious exposures."

New P1 trial • P1 data • P2 data • Alzheimer's Disease • CNS Disorders • Dementia

New Biomarker Data from the GAIN Trial of atuzaginstat (COR388) Link Target Inhibition with Efficacy in Reducing Cognitive Decline in P. gingivalis Infected Subjects with Mild-Moderate Alzheimer’s Disease (AAIC 2022) - No abstract available

Biomarker • Clinical • Alzheimer's Disease • CNS Disorders

COR388 (atuzaginstat): an investigational gingipain inhibitor for the treatment of Alzheimer disease. (PubMed, Expert Opin Investig Drugs) - "gingivalis is opsonized by Aβ42, is capable of entering the brain, and is an accelerant of neuropathologies in rodent models of AD. Thus, in our opinion, this bacteria is highly likely to be a pathogen capable of initiating or precipitating the progression of AD, which agrees with the pathogen hypothesis of clinical AD development."

Journal • Alzheimer's Disease • CNS Disorders • Dental Disorders • Immunology • Infectious Disease • Inflammation • Periodontitis

Cortexyme to Participate at 4th International Conference on Porphyromonas gingivalis and Related Species in Oral and Systemic Diseases (Businesswire) - “Cortexyme, Inc…announced that the company will participate at The 4th International Conference on Porphyromonas gingivalis and Related Species in Oral and Systemic Diseases (PgLouisville2022) taking place May 15-17, 2022 in Louisville, Kentucky. Cortexyme’s clinical advisory board member Mark Ryder, D.M.D., will provide an overview of GAIN Trial results and biomarker data examining the role of P. gingivalis in oral and systemic diseases.”

Biomarker • P2/3 data • Alzheimer's Disease • CNS Disorders

Cortexyme Provides New GAIN Trial Data at AD/PD 2022 Demonstrating Potential Benefit of Lysine Gingipain Inhibition in Mild to Moderate Alzheimer’s Population (Businesswire) - P2/3 | N=643 | GAIN (NCT03823404) | Sponsor: Cortexyme Inc. | “Target engagement and biomarker data expands understanding of the role of P. gingivalis and the potential benefit of lysine gingipain inhibition. Biomarker data and correlations to clinical outcomes consistent with the gingipain hypothesis. Cortexyme, Inc…presented new target engagement and biomarker data from the GAIN Trial at the AD/PD™ 2022 International Conference on Alzheimer’s and Parkinson’s Diseases….GAIN Trial findings support that atuzaginstat engaged the target, inhibiting lysine gingipains, which are essential to the survival of P. gingivalis. Lysine gingipain inhibition by atuzaginstat resulted in a 30% to 50% slowing of cognitive decline in the participants with high P. gingivalis load.”

P2/3 data • Alzheimer's Disease • CNS Disorders

Cortexyme to Present New GAIN Trial Data at AD/PD 2022 (Businesswire) - “Cortexyme, Inc…announced that the company will participate at the AD/PD™ 2022 International Conference on Alzheimer’s and Parkinson’s Diseases, which is a hybrid event taking place March 15-20, 2022 in Barcelona, Spain, as well as virtually. Cortexyme’s chief medical officer Michael Detke, MD, PhD, will present new GAIN Trial results and biomarker data examining the role of P. gingivalis in Alzheimer’s disease and the P. gingivalis-positive population, in addition to sharing study data that reinforces the efficacy of the company’s first-in-class gingipain inhibitor in slowing cognitive decline in Alzheimer’s disease with P. gingivalis. These new data analyses will be reviewed at AD/PD 2022 and at additional conferences as more data becomes available throughout 2022.”

Biomarker • P2/3 data • Alzheimer's Disease • CNS Disorders

GAIN Trial: Phase 2/3 Study of COR388 in Subjects With Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=643 | Completed | Sponsor: Cortexyme Inc. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2022 ➔ Jan 2022

Trial completion • Trial completion date • Alzheimer's Disease • CNS Disorders

ADDITIONAL DATA FROM THE PHASE 2/3 GAIN TRIAL OF COR388 (ATUZAGINSTAT) FOR THE TREATMENT OF MILD-MODERATE ALZHEIMER’S DISEASE (ADPD 2022) - P2/3 | "Atuzaginstat slowed cognitive decline in Alzheimer’s disease with P. gingivalis by approximately 50% on ADAS-cog. Additional analyses are pending and will be shared."

P2/3 data • Alzheimer's Disease • CNS Disorders

Increased levels of phospho-tau217 in neuron cultures and CVN mice infected with Porphyromonas gingivalis. (PubMed, Alzheimers Dement) - "P. gingivalis infected neuronal cell cultures and chronically infected CVN mice display elevated p-tau217. In vitro this was apparent at low infection levels that might reflect the physiological level of gingipain exposure. Phospho-tau217 is emerging as a specific biomarker for AD and these results further validate P. gingivalis-infected neuron cultures and mice as models for AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Infectious Disease • NOS2

Cortexyme Announces Clinical Hold on Atuzaginstat’s Investigational New Drug Application (Businesswire) - “Cortexyme, Inc…announced that the company received a letter from the U.S. Food and Drug Administration (FDA) on January 25, 2022 placing a full clinical hold on atuzaginstat’s (COR388) Investigational New Drug application (IND 134303). The company plans to provide additional updates pending continued engagement with FDA….The company intends to prioritize development of its next generation gingipain inhibitor, COR588, in Alzheimer’s disease. COR588 is currently completing a Phase 1 SAD/MAD study and results are expected in the second quarter 2022.”

FDA event • P1 data • Alzheimer's Disease • CNS Disorders

Top-line Results from the GAIN Trial: A Phase 2/3 Study of Atuzaginstat in Mild to Moderate Alzheimer’s Disease (CTAD 2021) - No abstract available

Late-breaking abstract • P2/3 data • Alzheimer's Disease • CNS Disorders

Cortexyme’s Atuzaginstat Slowed Cognitive Decline in Participants With Alzheimer’s Disease and P. Gingivalis Infection in Phase 2/3 GAIN Trial: Additional Top-line Data Presented at CTAD 2021 (Businesswire) - “Cortexyme, Inc…will present additional data from its Phase 2/3 GAIN Trial at the 14th Clinical Trials on Alzheimer's Disease Conference (CTAD 2021) as a part of the meeting’s Late-Breaking Readout Roundtable program today, Thursday, November 11, 2021, at 11:35 a.m. Eastern Time taking place in Boston, Massachusetts, as well as virtually. The presentation will expand on previously reported top-line results that demonstrated the relationship between the reduction of Porphyromonas gingivalis (P. gingivalis) infection and the slowing of cognitive decline in Alzheimer’s disease with atuzaginstat treatment in a prespecified population of patients based on diagnosis of infection.”

Late-breaking abstract • P2/3 data • Alzheimer's Disease • CNS Disorders

Cortexyme's Alzheimer's treatment fails to meet main goals in study (Yahoo Finance) - “Cortexyme Inc said on Tuesday its experimental oral pill failed to meet the main goals of improving cognitive and functional abilities in patients with mild-to-moderate Alzheimer's disease in a study. The drug, atuzaginstat, is designed to target the P. gingivalis bacteria found in the brain of patients suffering from the memory robbing disease. The mid-to-late stage study tested 643 patients and did not meet statistical significance in its goals, according to two scales measuring disease progression. In a group of patients with the bacteria detected in their saliva, the drug showed 57% slowing of cognitive decline on a commonly used test but failed to show significant benefits on another scale…”

Clinical data • Alzheimer's Disease • CNS Disorders

Cortexyme Reports GAIN Trial Data Demonstrated Relationship Between Reduction of P. gingivalis Infection and Slowing of Alzheimer’s Disease Progression (Businesswire) - P2/3, N=643; GAIN (NCT03823404); Sponsor: Cortexyme; "Cortexyme...reported top-line results from its Phase 2/3 GAIN Trial, a double-blind, placebo-controlled study evaluating the efficacy of atuzaginstat (COR388)...The 643-participant study in mild to moderate patients with Alzheimer’s disease did not meet statistical significance in its co-primary cognitive and functional endpoints as measured by ADAS-Cog11 and ADCS-ADL at end of the treatment period in the overall cohort....Significant benefits in this subgroup were not seen on the other co-primary, ADCS-ADL. The cognitive benefit of atuzaginstat in patients with high P. gingivalis infection was reinforced by similar results in multiple pre-specified infection related subgroups and with multiple methods of analysis."

P2/3 data • Alzheimer's Disease • CNS Disorders

Cortexyme to Present Results from the GAIN Trial: A Phase 2/3 Study of Atuzaginstat in Mild to Moderate Alzheimer’s Disease at CTAD 2021 (Businesswire) - "Cortexyme, Inc…a company advancing a pivotal Phase 2/3 trial in Alzheimer’s disease and a growing pipeline of therapeutics for degenerative diseases, today announced that it will participate at the upcoming 14^th Clinical Trials on Alzheimer's Disease (CTAD 2021) conference scheduled for November 9-12, 2021, in Boston, Massachusetts, as well as virtually. Cortexyme will present results from its Phase 2/3 GAIN Trial evaluating the efficacy of its lead small molecule atuzaginstat in 643 mild to moderate Alzheimer’s patients. Cortexyme expects to announce top-line results in advance of its scientific presentation at CTAD 2021. Results of the GAIN Trial’s Phase 2 periodontal disease REPAIR sub-study also are expected to be announced by mid-November."

P2/3 data • Alzheimer's Disease • CNS Disorders

Cortexyme Expands Proprietary Development Pipeline with Initiation of Phase 1 Clinical Trial of COR588 (Yahoo Finance) - “Cortexyme…today announced that the first cohort of healthy participants have been dosed in the Phase 1 clinical trial of its new drug candidate, COR588. COR588 is a second-generation small-molecule lysine-gingipain inhibitor differentiated from the company’s lead drug candidate atuzaginstat (COR388) by its improved pharmacokinetic properties and anticipated once daily oral administration. Delivering on its commitment to bring innovation to high unmet clinical needs, Cortexyme expects COR588 to be targeted for use in the treatment of periodontal disease and other P. gingivalis-related indications….The trial will enroll up to 64 participants…”

Trial status • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Cortexyme to Present at Annual Biomarkers for Alzheimer’s Disease Summit (Businesswire) - “Cortexyme, Inc…a company advancing a pivotal trial in Alzheimer’s disease with top-line data expected by mid-November 2021 and a growing pipeline of therapeutics for degenerative diseases, will participate as a featured speaker covering its pivotal Phase 2/3 GAIN Trial of atuzaginstat and the upstream role that P. gingivalis plays in key pathologies of Alzheimer’s disease at the upcoming Annual Biomarkers for Alzheimer’s Disease Summit taking place virtually August 24-26, 2021. Cortexyme will present new data demonstrating further evidence of P. gingivalis infection of the central nervous system in Alzheimer’s disease as demonstrated by analysis of anti-P. gingivalis antibodies in cerebrospinal fluid from the GAIN trial.”

P2/3 data • Alzheimer's Disease • CNS Disorders

Cortexyme Provides Business Update and Reports Second Quarter 2021 Results (Yahoo Finance) - "Pivotal GAIN Trial Top-line Data Expected by Mid-November 2021: Cortexyme is pioneering an innovative, upstream, disease-modifying therapeutic approach to Alzheimer's disease with the company’s pivotal Phase 2/3 GAIN Trial that enrolled 643 patients with mild to moderate Alzheimer’s disease…Research and Development (R&D) Expenses: For the quarter ended June 30, 2021, R&D expenses were $14.7 million primarily due to costs related to the research and development of atuzaginstat, the GAIN Trial, COR588, and personnel-related expenses."

Commercial • Enrollment status • P2/3 data • Alzheimer's Disease • CNS Disorders

An update and baseline data from the Phase 2/3 GAIN trial of COR388 (atuzaginstat) a novel bacterial virulence factor inhibitor for the treatment of Alzheimer’s Disease (CTAD 2021) - No abstract available

P2/3 data • Alzheimer's Disease • CNS Disorders

[VIRTUAL] Increased levels of phospho-tau217 in neuron cultures and CVN mice infected with Porphyromonas gingivalis (AAIC 2021) - "Tau degradation was completely inhibited by treatment with the specific Kgp inhibitor COR388 (atuzaginstat)... P. gingivalis infected neuronal cell cultures and chronically infected CVN mice display elevated p-tau217. In vitro this was apparent at low infection levels that might reflect the physiological level of gingipain exposure. Phospho-tau217 is emerging as a specific biomarker for AD and these results further validate P. gingivalis -infected neuron cultures and mice as models for AD."

Preclinical • Alzheimer's Disease • CNS Disorders • Infectious Disease • NOS2