What changed in this filing

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Item 1. Business

2021-03-01 compared with 2020-03-16 · 180 added, 146 removed, 394 unchanged (45% of the section changed)

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Our approach is based on the seminal discovery of the presence of Porphyromonas gingivalis , or P.

gingivalis , and its secreted toxic virulence factor proteases, called gingipains, in the brains of greater than 90% of more than 100 Alzheimer’s patients observed across multiple studies to date.

Additionally, we have observed that P.

gingivalis infection causes Alzheimer’s pathology in animal models, and these effects have been successfully treated with a gingipain inhibitor in preclinical studies.

Our proprietary lead drug candidate, COR388, is an orally administered, brain-penetrating small molecule gingipain inhibitor.

COR388 was well-tolerated with no concerning safety signals in our Phase 1a and Phase 1b clinical trials conducted to date, which enrolled a total of 67 subjects, including nine patients with mild to moderate Alzheimer’s disease.

We initiated a global Phase 2/3 clinical trial of COR388, called the GAIN trial, in mild to moderate Alzheimer’s patients in April 2019 in the United States and in September 2019 in Europe and expect top-line results by the end of 2021.

COR388 is the first and only selective inhibitor of gingipain activity being investigated in clinical trials for the treatment of Alzheimer’s disease.

COR388 is designed to target an upstream driver of multiple Alzheimer’s pathological pathways, including amyloid beta production, inflammation and neurodegeneration, in contrast to mechanisms of action targeting downstream effects, such as amyloid plaques and tau tangles, which have been largely unsuccessful in clinical trials to date.

Accordingly, we believe COR388 could represent a disease-modifying therapy for the chronic treatment of Alzheimer’s disease.

Our Phase 1a and Phase 1b clinical trials enrolled a total of 67 subjects, including nine patients with mild to moderate Alzheimer’s disease.

In these placebo-controlled trials, COR388 was well-tolerated with no concerning safety signals.

In the Alzheimer’s patients treated with COR388 for 28 days, we found changes in a number of pharmacodynamic biomarkers associated with Alzheimer’s disease, including RANTES, an inflammatory marker, and Apolipoprotein protein E, or ApoE, a target for gingipains.

For example, fragments of ApoE in the CSF were reduced compared to placebo, and blood levels of RANTES were significantly reduced.

In addition, data from the Alzheimer’s patients treated with COR388 in our Phase 1b clinical trial showed improvements across several exploratory cognitive tests.

These improvements in cognitive tests should be interpreted with caution because they were not all statistically significant.

We identified bacterial DNA from P.

gingivalis in the cerebral spinal fluid, or CSF, of all nine Alzheimer’s patients, and this finding is supported by additional data from larger studies conducted by our team both independently and in collaboration with academic institutions.

Moreover, we observed that COR388 successfully penetrated the blood-brain barrier.

In addition, in our preclinical studies, we observed that COR388 reduced bacterial load in the brain, reduced amyloid beta levels, protected neurons and reduced markers of neuroinflammation.

We plan to enroll approximately 570 mild to moderate Alzheimer’s patients in our Phase 2/3 GAIN trial, or GingipAIN Inhibitor for the Treatment of Alzheimer’s Disease Trial, to evaluate safety and efficacy after one year of treatment as measured on key endpoints that have previously supported regulatory approval of drugs for Alzheimer’s disease, including the Alzheimer’s disease Assessment Scale-Cognitive Subscale 11, or ADAS-Cog11.

We expect to report top-line data from this trial by the end of 2021.

In addition, we intend to conduct an interim analysis after approximately 100 patients in each of the GAIN trial’s three arms complete six months of treatment by the end of 2020.

gingivalis , and its secreted toxic virulence factor proteases, called gingipains, in the relevant brain areas of both Alzheimer’s and Parkinson’s disease patients.

Additionally, we and other researchers have observed that P.

gingivalis infection causes Alzheimer’s and Parkinson’s pathology in animal models, and these effects have been successfully treated with a gingipain inhibitor in preclinical studies.

Our proprietary lead drug candidate, atuzaginstat (COR388), is an orally administered, brain-penetrating small molecule gingipain protease inhibitor.

Atuzaginstat was well-tolerated with no concerning safety signals in our Phase 1a and Phase 1b clinical trials conducted to date, which enrolled a total of 74 subjects, including nine patients with mild to moderate Alzheimer’s disease.

We have fully enrolled a global pivotal Phase 2/3 clinical trial of atuzaginstat, called the GAIN ( GingipAIN Inhibitor for Treatment of Alzheimer’s Disease) trial, in mild to moderate Alzheimer’s patients.

We conducted an interim analysis in December 2020 after approximately 100 patients in each of the GAIN trial’s three arms completed 24 weeks of treatment.

Based on the successful interim analysis, topline data for the fully enrolled population of 643 subjects after the full 1-year treatment period is expected in Q4 2021.

Topline efficacy data in periodontal disease is expected from a prospective sub-study of 233 GAIN Trial subjects in Q4 2021.

The GAIN Trial included an open-label extension (OLE) in the United States that began enrollment in April 2020.

On February 12, 2021, we received a letter from the FDA stating that a partial clinical hold has been placed on atuzaginstat impacting the OLE phase of the GAIN Trial.

The partial clinical hold was initiated following the review of hepatic adverse events in the atuzaginstat trial by the FDA.

These events have been reversible and without any known long-term adverse effects for the participants.

Under the hold, we have stopped enrollment and dosing in the OLE phase of the GAIN Trial.

Atuzaginstat is the first and only selective inhibitor of gingipain activity being investigated in clinical trials for the treatment of neurodegenerative disease.

Atuzaginstat is designed to target an upstream driver of multiple pathological pathways, including amyloid beta production, inflammation and neurodegeneration, in contrast to mechanisms of action targeting downstream effects, such as amyloid plaques and tau tangles, which have been largely unsuccessful in clinical trials to date.

Accordingly, we believe atuzaginstat could represent a disease-modifying therapy for the chronic treatment of neurodegenerative disease.

COR588 is a second generation brain penetrant lysine gingipain inhibitor currently in IND enabling studies that will initially be positioned in periodontal disease with potential efficacy in multiple indications.

We anticipate initiating clinical studies in Q3 2021.

COR788 and COR822 are lead arginine gingipain inhibitors with therapeutic potential in various P.

gingivalis related diseases.

Alzheimer’s disease represents one of the most significant unmet medical needs of our time and there are no marketed treatments that address the underlying cause of the disease.

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Our drug candidate has demonstrated proof of concept in a new physiological animal model that we believe is representative of human Alzheimer’s disease pathology.

Understanding the Foundation of Our Therapeutic Approach

gingivalis is an intracellular bacterial pathogen, and its gingipains are essential for P.

gingivalis survival and pathogenicity.

Our new understanding of the P.

gingivalis brain infection and associated gingipain production, which we have observed to cause Alzheimer’s pathology in animal models, provides a new opportunity for successful upstream treatment of all aspects of Alzheimer’s disease pathology.

Significant evidence in the last decade has shown that neurodegenerative diseases, including Alzheimer’s disease, are linked to a dysfunctional immune system.

Furthermore, the pathology of Alzheimer’s disease has been shown in studies to be consistent with that of infection, including, for example, the pathological presence of amyloid beta, which recently has been characterized as an antimicrobial peptide produced in response to infection.

In preclinical mouse models, we and others have demonstrated that P.

gingivalis is capable of accessing the brain and that its presence causes amylo id beta production, inflammation and neurodegeneration, which are characteristic pathology observed in the brain of Alzheimer’s patients.

gingivalis and gingipains have been observed in the brains of greater than 90% of more than 100 Alzheimer’s patient s across multiple studies conducted by our team both independently and in collaboration with academic institutions.

Our Lead Drug Candidate-COR388

We have discovered and developed a proprietary library of protease inhibitors from which we have selected our lead drug candidate, COR388, an orally administered, brain-penetrating small molecule being developed for chronic treatment of Alzheimer’s disease.

We believe that the development of this compound represents a new paradigm for potential disease modification in Alzheimer’s disease, based on our published and unpublished data, as well as a large body of third-party research.

We maintain rights to COR388 and hold issued U.S.

patents providing composition of matter coverage through 2035 and pending U.S.

Parkinson’s disease affects more than 1 million people in the United States and 10 million worldwide.

Currently approved treatments are limited to primarily managing symptoms.

Based upon the evidence to date, our S tart-up activities for a Phase 2 study in early Parkinson’s disease called the PEAK (Gingipain inhibitor for treatment of PArKinsons’ disease) Trial have been initiated and first patient in is expected in Q3 2021.

gingivalis has been identified as a key pathogen in the development of periodontal disease.

Periodontal disease is a common age-related disease affecting nearly 50% of the population over 50 years of age, or 65 million people, in the United States.

The disease presents with symptoms including chronic inflammation, degeneration of gum tissue and tooth loss.

Periodontal disease is associated with increased risk of cardiovascular disease, diabetes and certain cancers.

The disease is often chronic and recurring due to persistent bacterial infection and antibiotic resistance.

Current standard of care for the treatment of periodontal disease commonly involves scaling and root planning to remove bacterial plaque and tartar, in addition to local delivery of antibiotics in some cases.

Atuzaginstat (COR388) reduced periodontal disease and associated bone loss in multiple animal models of periodontal disease.

Target engagement and efficacy data for atuzaginstat (COR388) in aged dogs was published in January 2020 in the journal Pharmacology Research and Perspectives .

Partial Clinical Hold

On February 12, 2021 the Company received a letter from the FDA stating that a partial clinical hold has been placed on atuzaginstat (COR388) impacting the open-label extension (OLE) phase of the company’s ongoing Phase 2/3 study, the GAIN Trial.

Under the hold, no new participants will be enrolled in the OLE and currently enrolled OLE participants will be discontinued.

Participants in the fully enrolled (N=643) double-blind, placebo-controlled randomized phase of the GAIN Trial will continue to receive study drug at their assigned dose.

The partial clinical hold was initiated following the review of hepatic adverse events in the atuzaginstat trial by the FDA.

These events have been reversible and without any known long-term adverse effects for the participants.

Cortexyme will continue to collaborate with the FDA on the overall development program for atuzaginstat.

Business Update Regarding COVID-19

The current COVID-19 pandemic has presented a substantial public health and economic challenge around the world and is affecting our employees, patients, communities and business operations, as well as the U.S.

economy and financial markets.

The full extent to which the COVID-19 pandemic will directly or indirectly impact our business, results of operations and financial condition will depend on future developments that are highly uncertain and cannot be accurately predicted, including new information that may emerge concerning COVID-19, the actions taken to contain it or treat its impact and the economic impact on local, regional, national and international markets.

To date, our employees, vendors and clinical trial sites have been able to advance our GAIN clinical trial, complete enrollment and continue the Open Label Extension for eligible patients completing the GAIN trial.

At this time the impact of the COVID-19 pandemic has not resulted in changes to our previously stated analysis timelines for the GAIN trial.

We are continuing to assess the potential impact of the COVID-19 pandemic on our business and operations, including our expenses, preclinical operations and clinical trials.

Our office-based employees have been working primarily from home since mid-March 2020, while ensuring essential staffing levels in our operations remain in place, including maintaining key personnel in our lab facility.

We have developed plans to enable all employees to voluntarily return to work in our offices and lab facility which include safety protocols, such as face coverings, social distancing, frequent cleaning, and COVID-19 testing.

We continue to assess the risks which take into account applicable public health authority and local government guidelines and are designed to ensure community and employee safety.

However, the effects of the COVID-19 pandemic continue to rapidly evolve and even if our employees more broadly return to work in our offices and lab facility, we may have to resume a more restrictive remote work model, whether as a result of spikes or surges in COVID-19 infection or hospitalization rates or public authority mandates.

We are not currently experiencing any significant supply chain disruptions and have drug supply for the full GAIN Trial on hand.

We have diversified our vendor relationships geographically for both starting materials and manufacturing.

However, in the future, the ongoing COVID-19 pandemic, may result in the inability of some of our suppliers to deliver drug supplies on a timely basis.

We have taken and continues to take proactive measures to maintain the integrity of its ongoing clinical trial.

To potentially mitigate some of the risks of COVID-19 and based on interest and the ability to maintain milestone timelines, we enrolled approx imately an additional 70 subjects in the GAIN trial.

Despite these efforts, the COVID-19 pandemic could impact timelines, subject follow up visits and study completion.

We will continue to monitor the COVID-19 situation and its impact on the ability to continue the development of, and seek regulatory approvals for, our product candidates.

For additional information on the various risks posed by the COVID-19 pandemic, please read Item 1A.

Risk Factors included in this report.

Our Lead Drug Candidate - Atuzaginstat (COR388)

We have discovered and developed a proprietary library of protease inhibitors from which we have selected our lead drug candidate, atuzaginstat (COR388) , an orally administered, brain-penetrating small molecule being developed for chronic treatment of Alzheimer’s disease, Parkinson’s disease and periodontal disease.

We believe that the development of this compound represents a new paradigm for disease modification, based on our published and unpublished data, as well as a large body of third-party research.

We maintain rights to atuzaginstat and hold two issued U.S.

patents providing composition of matter coverage through at least 2037 and pending U.S.

and foreign patent applications, which, if issued, could extend coverage.

Summary of Our Clinical and Preclinical Data

We have completed two Phase 1 clinical trials for COR388 which enrolled 67 subjects, including nine patients with mild to moderate Alzheimer’s disease.

We believe the following clinical and preclinical data generated to date by COR388 support its development as a potential disease-modifying treatment for Alzheimer’s disease:

We tested COR388 in two placebo-controlled Phase 1 clinical trials:

(i) a Phase 1a single ascending dose, or SAD, study in 34 healthy volunteers and (ii) a Phase 1b multiple ascending dose, or MAD, study in 24 older healthy volunteers and nine Alzheimer’s patients.

We observed COR388 to be well-tolerated with no concerning safety signals.

Our Phase 1 clinical trials also demonstrated that COR388 affected a number of pharmacodynamic biomarkers associated with Alzheimer’s disease, including blood levels of RANTES and fragments of ApoE in the CSF.

Additionally, although not powered for statistical significance, in our Phase 1b clinical trial, data from the small group of Alzheimer’s patients treated with COR388 showed improvements across several exploratory cognitive tests including:

We have completed three Phase 1 a/b clinical trials for a tuzaginstat which enrolled 74 subjects, including nine patients with mild to moderate Alzheimer’s disease.

We believe the following clinical and preclinical data generated to date by a tuzaginstat support its development as a potential disease-modifying treatment for Alzheimer’s disease:

We have tested a tuzaginstat in two placebo-controlled and one open label Phase 1 clinical trials:

(i) a Phase 1a single ascending dose, or SAD, study in 34 healthy volunteers (ii) a Phase 1b multiple ascending dose, or MAD, study in 24 older healthy volunteers and nine Alzheimer’s patients and (iii) a Phase 1 open label single dose study to determine the absorption, metabolism, and excretion (AME) of [C 14 ]-atuzaginstat (COR388) in healthy male volunteers .

We observed a tuzaginstat to be well-tolerated with no concerning safety signals.

Our Phase 1 clinical trials also demonstrated that a tuzaginstat affected a number of pharmacodynamic biomarkers associated with Alzheimer’s disease, including blood levels of RANTES and fragments of ApoE in the CSF.

Additionally, although not powered for statistical significance, in our Phase 1b clinical trial, data from the small group of Alzheimer’s patients treated with a tuzaginstat showed improvements across several exploratory cognitive tests including:

a statistically significant improvement in three measures on the Winterlight speech-based cognitive assessment, or WLA, relative to baseline;

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In our preclinical studies using wild type mice infected with P.

gingivalis , we have observed that gingipain inhibitors, including COR388, prevented further neurodegeneration, reduced amyloid beta levels and reduced markers of neuroinflammation.

gingivalis , we have observed that gingipain inhibitors, including atuzaginstat , prevented further neurodegeneration, reduced amyloid beta levels and reduced markers of neuroinflammation.

In our preclinical chronic toxicology studies, ranging from six to nine months in length, we observed a large potential therapeutic window with no adverse findings or dose-limiting toxicities after chronic administration.

Our Phase 2/3 GAIN Clinical Trial of COR388 in Mild to Moderate Alzheimer’s Patients

We initiated a global Phase 2/3 randomized, double-blind, placebo-controlled study in April 2019, which we refer to as the GingipAIN Inhibitor for the Treatment of Alzheimer’s Disease, or GAIN, trial.

This study is designed to assess the efficacy, safety and tolerability of two dose levels of COR388 (40 mg and 80 mg) in subjects with mild to moderate Alzheimer’s disease compared to placebos.

The study is intended to enroll approximately 570 male and female subjects between the ages of 55 and 80.

Enrolled subjects must have a diagnosis of mild to moderate Alzheimer’s disease dementia, with MMSE scores between 12 and 24 points, a range that is documented to provide an average decline in the placebo group sufficient to show efficacy of a disease slowing treatment over a one-year treatment period.

Randomization will be stratified by baseline MMSE and ApoE4 genotype to assure balanced distribution of mild and moderate Alzheimer’s disease and a balanced distribution of ApoE4 carriers, across treatment arms.

Patients will be able to remain on stable doses of background medications, including symptomatic Alzheimer’s disease treatments, during the trial.

The study will consist of a treatment period of up to 48 weeks and a safety follow-up period of 6 weeks.

Periodic safety reviews will be conducted during the study.

All supporting studies to update the COR388 IND, including the GAIN trial protocol, chronic toxicology studies and metabolite studies, have been submitted to the FDA and have completed the 30-day review period indicating acceptance of the IND update and clearance to proceed with the Phase 2/3 GAIN trial.

Following discussion with the FDA in February 2020, we also intend to conduct an interim analysis for overwhelming efficacy in our GAIN trial.

We plan to conduct the interim analysis by the end of 2020 after approximately 100 patients in each of the GAIN trial’s three arms complete six months of treatment.

The co-primary endpoints will be the mean change in ADAS-Cog11 and change in Clinical Dementia Rating-Sum of Boxes, CDR-SB from baseline to the end of treatment period at 48 weeks versus placebo.

A secondary endpoint in all subjects will include change in Alzheimer’s Disease Cooperative Study Group-Activities of Daily Living, or ADCS-ADL.

Our Phase 2/3 GAIN Clinical Trial of atuzaginstat in Mild to Moderate Alzheimer’s Patients

We have fully enrolled an ongoing global Phase 2/3 randomized, double-blind, placebo-controlled study which was initiated in April 2019, called the GAIN Trial (GingipAIN Inhibitor for the Treatment of Alzheimer’s Disease).

This study is designed to assess the efficacy, safety and tolerability of two dose levels of atuzaginstat ( 40 mg and 80 mg twice daily) in subjects with mild to moderate Alzheimer’s disease compared to placebo.

The study enrolled 643 male and female subjects between the ages of 55 and 80.

Enrolled subjects have a diagnosis of mild to moderate Alzheimer’s disease dementia, with MMSE scores between 12 and 24 points, a range that is documented to provide an average decline in the placebo group sufficient to show efficacy of a disease slowing treatment over a one-year treatment period.

Randomization was stratified by baseline MMSE and ApoE4 genotype to assure balanced distribution of mild and moderate Alzheimer’s disease and a balanced distribution of ApoE4 carriers, across treatment arms.

Patients are able to remain on stable doses of background medications, including symptomatic Alzheimer’s disease treatments, during the trial.

The study consists of a treatment period of up to 48 weeks and a safety follow-up period of 6 weeks.

Periodic safety reviews are conducted by an independent Data Monitoring Committee (“DMC”) throughout the study.

An interim analysis was conducted when approximately 300 patients reached 6 months of treatment.

As part of the interim analysis, the DMC looked for futility (p< 0.05 favoring placebo), overwhelming efficacy (p< 0.005 on both co-primary outcomes), a sample size increase if needed to improve powering, as well as safety.

Based on the interim analysis, the DMC recommended continuation without a sample size adjustment and topline data for the fully enrolled population of 643 subjects after the 1-year treatment period is expected on time in Q4 2021.

The co-primary endpoints will be the mean change in ADAS-Cog11 and change in Alzheimer’s Disease Cooperative Study Group-Activities of Daily Living, or ADCS-ADL from baseline to the end of treatment period at 48 weeks versus placebo.

A secondary endpoint in all subjects will include change in Clinical Dementia Rating-Sum of Boxes, CDR-SB.

Exploratory endpoints will include change from baseline to the end of treatment period in the following measures:

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and (v) MRI brain measurements.

Additionally, periodontal disease, including pocket depth and bleeding on probing, will be tracked in a subset of patients.

For the interim analysis, the co-primary endpoints will be change from baseline in ADAS-Cog11 and CDR-SB versus placebo.

Placebo and treated patients who complete our Phase 2/3 GAIN trial in the United States may be eligible to participate in an open label extension in which patients will receive 80 mg COR388 twice daily.

The purpose of this extension study is to evaluate the long-term safety and tolerability of COR388 as well as encourage patient enrollment and retention.

Additionally, periodontal disease, including pocket depth and bleeding on probing, are being measured at 6 months and 1 year in a subset of 233 patients.

For the interim analysis, the co-primary endpoints were the change from baseline in ADAS-Cog11 and CDR-SB versus placebo.

Placebo and treated patients who complete our Phase 2/3 GAIN trial in the United States may be eligible to participate in an open label extension in which patients will receive 40 or 80 mg atuzaginstat (COR388) twice daily.

The purpose of this extension study is to evaluate the long-term safety and tolerability of atuzaginstat as well as encourage patient enrollment and retention.

The Planned Phase 2 PEAK trial in early Parkinson’s disease

We recently initiated start-up activities for a potential Phase 2 study of atuzaginstat in Parkinson’s disease and expect our first patient to start being dosed in Q3 2021.

Our objective is to transform the treatment of Alzheimer’s and other degenerative diseases by creating a broad portfolio of innovative therapeutics that target significant unmet medical needs.

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To achieve this objective, we are pursuing the following strategies:

Rapidly advance COR388 through clinical development in patients with Alzheimer’s disease.

Based on the strength of the data we observed in our two completed Phase 1 clinical trials, we initiated a Phase 2/3 randomized, double-blind, placebo-controlled trial in April 2019 that is designed to assess the efficacy, safety and tolerability of COR388 in mild to moderate Alzheimer’s patients.

Develop COR388 for other diseases.

Rapidly advance atuzaginstat through clinical development and NDA filing for treatment of Alzheimer’s disease.

Develop atuzaginstat for other diseases.

gingivalis infection and associated protein-cleaving, or proteolytic, gingipain activity have been implicated in multiple disease pathologies in preclinical and epidemiological studies.

We plan to conduct clinical trials of COR388 in other indications where both human observational data and preclinical experiments support its therapeutic potential.

We plan to conduct clinical trials of atuzaginstat in other indications where both human observational data and preclinical experiments support its therapeutic potential.

Expand our portfolio by developing additional compounds.

A key element of our portfolio strategy is to advance additional molecules from our proprietary library.

We have initiated several other protease inhibitor programs.

We have initiated several other protease inhibitor programs including COR588 for potential treatment of periodontal disease and 3CL pro inhibitors for potential treatment of coronaviruses.

Additionally, we are developing a positron emission tomography, or PET, imaging agent for detection of gingipains in the human brain and advancing candidate compounds through lead optimization.

Optimize value of COR388 and future drug candidates in major markets.

We own rights to COR388 and our library of compounds.

We plan to develop and pursue approval of COR388 and other future drug candidates in major markets.

Optimize value of atuzaginstat and future drug candidates in major markets.

We own rights to COR388, COR588, COR788 and our entire library of compounds.

We plan to develop and pursue approval of atuzaginstat and other future drug candidates in major markets.

Where appropriate, we may use strategic collaborations and partnerships to accelerate the development and maximize the commercial potential of our programs.

Pipeline Com pounds

We have a library of small molecule protease inhibitors, including additional gingipain inhibitors with structures that are distinct from COR388.

Pipeline Compounds

We have a library of small molecule protease inhibitors, including additional gingipain inhibitors with structures that are distinct from atuzaginstat.

gingivalis expresses two types of gingipains, lysine and arginine gingipain, both of which appear to be essential for toxicity and bacterial survival.

The most advanced of the lysine gingipain (Kgp) inhibitors, aside from COR388, have been shown to be potent at less than 100 picomolar concentrations, highly selective for Kgp versus human anti-targets and to possess good oral bioavailability, favorable pharmacokinetic profiles and sufficient brain levels in multiple preclinical species.

The most advanced of the lysine gingipain (Kgp) inhibitors, aside from atuzaginstat, have been shown to be potent at less than 100 picomolar concentrations, highly selective for Kgp versus human anti-targets and to possess good oral bioavailability, favorable pharmacokinetic profiles and sufficient brain levels in multiple preclinical species.

In a 28-day toxicology study in mice, these compounds were dosed with exposures significantly above predicted levels needed for efficacy with no changes in clinical pathology laboratory parameters, no clinical observations and no brain histopathology findings.

Based on these beneficial properties, COR588 has been selected to enter IND enabling studies and first in human clinical trials are expected in Q3 2021.

Our library of inhibitors also includes a series of arginine gingipain (Rgp) inhibitor lead compounds.

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These probe reagents are utilized in biomarker studies helping to establish target potency and inhibition in studies.

We are additionally screening our library of cysteine protease inhibitors for efficacy in other indications, including for the treatment of coronaviruses via inhibition of a cysteine protease required for replication, called 3CLpro.

We are additionally leveraging our library of inhibitors to develop a positron emission tomography, or PET, imaging agent for detection of gingipains in the human brain.

We are seeking to identify candidates and planning to advance a PET agent through lead optimization.

Coronavirus, including SARS-COV2, which causes COVID-19 express a protease that is critical for viral replication called 3CL protease (also called Main Protease, or MPro).

We have invented novel small molecule inhibitors of the 3CL protease of SARS-CoV-2 and other coronaviruses which block viral replication in cells.

Cortexyme is continuing to screen analogs for potency, selectivity, pharmacokinetics, in vivo efficacy and toxicology to identify candidate molecules for futher progression.

Additionally, we are leveraging our library of inhibitors to work towards development of a positron emission tomography, or PET, imaging agent for detection of gingipains in the human brain.

We are currently screening potential candidate compounds.

Additional Markets of Interest

Periodontal Disease

gingivalis has been identified as a key pathogen in the development of periodontal disease.

Periodontal disease is a common age-related disease affecting nearly 50% of the population over 50 years of age, or 65 million people, in the United States.

The disease presents with symptoms including chronic inflammation, degeneration of gum tissue and tooth loss.

Periodontal disease is associated with increased risk of cardiovascular disease, diabetes and certain cancers.

The disease is often chronic and recurring due to persistent bacterial infection and antibiotic resistance.

COR388 reduced periodontal disease and associated bone loss in multiple animal models of periodontal disease.

Target engagement and efficacy data for COR388 in aged dogs was published in January 2020 in the journal Pharmacology Research and Perspectives .

In our Phase 2/3 GAIN trial periodontal pocket depth is being assessed as an exploratory endpoint.

Other Systemic Disease Indications

gingivalis infection has been associated with disease pathology in a number of large market opportunities including atherosclerosis, diabetes, cancer and arthritis.

We continue to conduct preclinical research in physiological animal models representing these disease states to assess the potential for other novel gingipain inhibitors in our portfolio to be disease modifying.

gingivalis infection has been associated with disease pathology in a number of large market opportunities including atherosclerosis, diabetes, cancer, pre-term birth and arthritis.

We continue to conduct preclinical research in physiological animal models representing these disease states to assess the potential for gingipain inhibitors in our portfolio to be disease modifying.

Manufacturing

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We rely on third-party contract manufacturing organizations, or CMOs, to manufacture and supply our preclinical and clinical materials to be used during the development of our drug candidates.

We currently have sufficient COR388 on hand in the United States to complete our Phase 2/3 GAIN trial in Alzheimer’s disease as currently planned and ongoing preclinical studies.

Additional cGMP drug substance campaigns with our contract manufacturer and suppliers in various countries in Asia and Europe are in process to ensure full supply for our open label extension, ongoing product development campaigns, and additional clinical studies of COR388.

COR388 is a low molecular weight compound isolated as a stable crystalline solid.

We believe the synthesis of COR388 is reliable and reproducible from readily available starting materials, and the synthetic routes are amenable to large-scale production and do not require unusual equipment or handling in the manufacturing process.

We currently have sufficient atuzaginstat on hand in the United States to complete our Phase 2/3 GAIN trial in Alzheimer’s disease as currently planned and ongoing preclinical studies.

Additional cGMP drug substance campaigns with our contract manufacturers and suppliers in various countries in Asia and Europe are in process to ensure full supply for ongoing product development campaigns and additional clinical studies of atuzaginstat.

Atuzaginstat is a low molecular weight compound isolated as a stable crystalline solid.

We believe the synthesis of atuzaginstat is reliable and reproducible from readily available starting materials, and the synthetic routes are amenable to large-scale production and do not require unusual equipment or handling in the manufacturing process.

We are in the process of further optimizing the synthetic route for commercial manufacturing as well as developing related methodologies for the production of analog compounds in our pipeline.

We expect to continue to identify and develop drug candidates that are amenable to cost-effective production at CMOs.

Ou r COR388 drug product is currently neat powder in a capsule which has demonstrated stability for 6 months enabling a shelf life of 18 months at room temperature.

Drug substance has demonstrated stability for 24 months enabling a retest date of 36 months wh en stored refrigerated.

Stability studies are ongoing and we are currently optimizing a formulated drug product to be marketed.

Currently our drug substance is stored refrigerated, out of an abundance of caution while stability studies are ongoing, while t he storage condition for our drug product is room temperature.

We have established relationships with several key CMOs to enable both the non-clinical and clinical supply lines for COR388 active pharmaceutical ingredient, or drug substance, as well as drug product under cGMP protocols.

Our atuzaginstat drug product is currently neat powder in a capsule which has demonstrated stability for 12 months enabling a shelf life of 24 months at room temperature.

Drug substance has demonstrated stability for 36 months enabling a retest date of 48 months when stored refrigerated.

We have optimized a new formulated drug product to be marketed which we plan to use in future clinical studies.

Currently our drug substance is stored refrigerated, out of an abundance of caution while stability studies are ongoing, while the storage condition for our drug product is room temperature.

We have established relationships with several key CMOs to enable both the non-clinical and clinical supply lines for atuzaginstat active pharmaceutical ingredient, or drug substance, as well as drug product under cGMP protocols.

To date the cGMP drug substance manufacturing process has been completed with a single vendor from readily available commercial starting materials and reagents.

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We face competition from a number of different sources, including large and specialty pharmaceutical and biotechnology companies, academic research institutions, governmental agencies and public and private research institutions.

We believe that the key competitive factors affecting the success of COR388 and any other drug candidates will include efficacy, safety profile, method of administration, cost, level of promotional activity and intellectual property protection.

We believe that the key competitive factors affecting the success of atuzaginstat and any other drug candidates will include efficacy, safety profile, method of administration, cost, level of promotional activity and intellectual property protection.

We know of no competitors developing clinical stage therapeutics targeting P.

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Our drug candidates, if successfully developed and approved, will compete with current therapies approved for the treatment of Alzheimer’s disease, which to date have been primarily targeted at treating the symptoms of such diseases rather than halting or slowing the progression of the disease.

However, in addition to such currently approved therapies, we believe that our drug candidates, if approved, may also compete with other potential therapies intended to halt or slow the progression of neurodegenerative disease that are being developed by a number of companies and institutions, including but not limited to potentially disease modifying therapeutics that are being developed by several large and specialty pharmaceutical and biotechnology companies, including AbbVie Inc., Biogen Inc., Eli Lilly and Company, Eisai Co., Ltd., Merck & Company, Inc., Novartis AG and Roche Holding AG (including Genentech, its wholly owned subsidiary), as well as companies pursuing a dysfunctional immune system approach to Alzheimer’s disease or other types of therapies.

However, in addition to such currently approved therapies, we believe that our drug candidates, if approved, may also compete with other potential therapies intended to halt or slow the progression of neurodegenerative disease that are being developed by a number of companies and institutions, including but not limited to potentially disease modifying therapeutics that are being developed by several large and specialty pharmaceutical and biotechnology companies, including AbbVie Inc., Biogen Inc., Eli Lilly and Company, Eisai Co., Ltd., Merck & Company, Inc., Denali Therapeutics, Inc., Alector, Inc., Cassava Sciences, Inc., Biohaven Pharmaceuticals, Inc., Novartis AG and Roche Holding AG (including Genentech, its wholly owned subsidiary), as well as companies pursuing a dysfunctional immune system approach to Alzheimer’s disease or other types of therapies.

Intellectual Property

We maintain rights to COR388 and hold issued U.S.

patents providing composition of matter and method of use coverage through 2035.

We maintain rights to atuzaginstat and hold issued U.S.

patents providing composition of matter and method of treatment coverage of atuzaginstat through 2037.

We hold issued foreign patents providing composition of matter and medical use coverage of atuzaginstat in Australia, Austria, Belgium, China, Colombia, Croatia, Cyprus, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Iceland, Ireland, Italy, Japan, Luxembourg, the Netherlands, Norway, Poland, Portugal, Romania, Russia, Spain, Sweden, Switzerland, Turkey, and the United Kingdom through 2035.

We also hold pending U.S.

and foreign patent applications, which, if issued, could extend coverage for COR388.

Our foreign patent applications are currently pending in Argentina, Australia, Brazil, Canada, Chile, China, Colombia, the European Patent Office, Hong Kong, Israel, India, Japan, South Korea, Mexico, Malaysia, New Zealand, Peru, the Philippines, Russia, Singapore, Taiwan, and South Africa.

Other patent families in our patent portfolio disclose and claim other small-molecule inhibitors of lysine gingipain and arginine gingipain, gingipain activity probes for biological imaging, and assay methods for the detection of microbial pathogens in cerebrospinal fluid and other bodily fluids.

and foreign patent applications, which, if issued, could create new protection or extend coverage for atuzaginstat (COR388) and pipeline molecules:

COR588, and COR788.

Other patent families in our patent portfolio disclose and claim other small-molecule inhibitors of lysine gingipain and arginine gingipain, gingipain activity probes for biological imaging, coronavirus protease inhibitors, and assay methods for the detection of microbial pathogens in cerebrospinal fluid and other bodily fluids.

As with other biotechnology and pharmaceutical companies, our ability to maintain and solidify our proprietary and intellectual property position for our drug candidates and technologies will depend on our success in obtaining effective patent claims and enforcing those claims if granted.

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If third parties prepare and file patent applications in the United States or other jurisdictions that also claim technology or therapeutics to which we have rights, we may have to participate in interference proceedings, post-grant review, reissue, or reexamination in the USPTO and equivalent foreign courts to determine priority rights of invention, which could result in substantial costs to us even if the eventual outcome, which is highly unpredictable, is favorable to us.

patent may expire or remain in force for only a short period follow ing commercialization, thereby limiting any protection such patent would afford the respective product and any competitive advantage such patent may provide.

For more information regarding the risks related to our intellectual property, see “Risk Factors—R isks Related to Our Intellectual Property.”

In addition, because of the extensive time required for clinical development and regulatory review of a drug candidate we may develop, it is possible that, before any of our drug candidates can be commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby limiting any protection such patent would afford the respective product and any competitive advantage such patent may provide.

For more information regarding the risks related to our intellectual property, see “Risk Factors—Risks Related to Our Intellectual Property.”

The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

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requirements at any time during the product development process, approval process or post-market may subject an applicant to administrative or judicial sanctions.

These sanctions could include, among other actions, the FDA’s refusal to

approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, product recalls or market w ithdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement and civil or criminal penalties.

These sanctions could include, among other actions, the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, product recalls or market withdrawals, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement and civil or criminal penalties.

An applicant seeking approval to market and distribute a new drug product in the United States must typically undertake the following:

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For example, a specific protocol or part of a protocol is not allowed to proceed, while other protocols may do so.

Following issuance of a clinical hold or partial clinical hold, an investigation may only resume after the FDA has notified the sponsor that the investigation

The FDA will base that determination on information provided by the sponsor correcting the deficiencies previously cited or o therwise satisfying the FDA that the investigation can proceed.

Following issuance of a clinical hold or partial clinical hold, an investigation may only resume after the FDA has notified the sponsor that the investigation may proceed.

The FDA will base that determination on information provided by the sponsor correcting the deficiencies previously cited or otherwise satisfying the FDA that the investigation can proceed.

A sponsor may choose, but is not required, to conduct a foreign clinical study under an IND.

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The GAIN trial combines a Phase 2 dose-finding design to identify the optimal dosage, with a Phase 3 magnitude of enrollment adequate to statistically evaluate the efficacy and safety.

For indications like Alzheimer’s disease with cognitive endpoints requiring a large number of subjects for sufficient

powering to demonstrate convincing efficacy, it may be beneficial to advance rapidly to Phase 3 when the investigational drug is relativ ely well tolerated and is not producing concerning safety signals.

For indications like Alzheimer’s disease with cognitive endpoints requiring a large number of subjects for sufficient powering to demonstrate convincing efficacy, it may be beneficial to advance rapidly to Phase 3 when the investigational drug is relatively well tolerated and is not producing concerning safety signals.

In other indications or for other therapeutics, a smaller Phase 2 (or even a Phase 2a followed by a Phase 2b) may be useful and appropriate prior to progression to a larger Phase 3 study.

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Thus, accelerated approval has been used extensively in the development and approval of drugs for treatment of a variety of cancers in which the goal of therapy is generally to improve survival or decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large trials to demonstrate a clinical or survival benefit.

The accelerated approval pathway is usually contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval c onfirmatory studies to verify and describe the drug’s clinical benefit.

The accelerated approval pathway is usually contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the drug’s clinical benefit.

As a result, a drug candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of Phase 4 or post-approval clinical trials to confirm the effect on the clinical endpoint.

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Drugs may be promoted only for the approved indications and in accordance with the provisions of the approved label.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promo ted off-label uses may be subject to significant liability.

The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to significant liability.

In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, which regulates the distribution of drugs and drug samples at the federal level, and sets minimum standards for the registration and regulation of drug distributors by the states.

Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution.

The 21st Century Cures Act

On December 13, 2016, then-President Obama signed 21st Century Cures Act, or the Cures Act, into law.

The Cures Act is designed to modernize and personalize healthcare, spur innovation and research, and streamline the discovery and development of new therapies through increased federal funding of particular programs.

It authorizes increased funding for the FDA to spend on innovation projects.

Further, the Cures Act directs the Centers for Disease Control and Prevention to expand surveillance of neurological diseases.

Regulation Outside the United States

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The Centralized Procedure is optional for products containing a new active substance not yet authorized in the EEA, or for products that constitute a significant therapeutic, scientific or technical innovation or which are in the interest of public health in the EU.

National MAs, which are issued by the co mpetent authorities of the Member States of the EEA and only cover their respective territory, are available for products not falling within the mandatory scope of the Centralized Procedure.

Where a product has already been authorized for marketing in a Me mber State of the EEA, this National MA can be recognized in another Member States through the Mutual Recognition Procedure.

National MAs, which are issued by the competent authorities of the Member States of the EEA and only cover their respective territory, are available for products not falling within the mandatory scope of the Centralized Procedure.

Where a product has already been authorized for marketing in a Member State of the EEA, this National MA can be recognized in another Member States through the Mutual Recognition Procedure.

If the product has not received a National MA in any Member State at the time of application, it can be approved simultaneously in various Member States through the Decentralized Procedure.

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The competent authority of the RMS prepares a draft assessment report, a draft summary of the product characteristics, or SPC, and a draft of the labeling and package leaflet, which are sent to the other Member States (referred to as the Member States Concerned) for their approval.

If the Member States Concerned raise no objections, based on a potential serious risk to public health, to the assessment, SPC, labeling or packaging proposed by the RMS, the product is subseq uently granted a national MA in all the Member States (i.e., in the RMS and the Member States Concerned).

If the Member States Concerned raise no objections, based on a potential serious risk to public health, to the assessment, SPC, labeling or packaging proposed by the RMS, the product is subsequently granted a national MA in all the Member States (i.e., in the RMS and the Member States Concerned).

Under the above described procedures, before granting the MA, the EMA or the competent authorities of the Member States of the EEA make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.

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The prescription drug plans negotiate pricing with manufacturers and may condition formulary placement on the availability of manufacturer discounts.

Since 2011, manufacturers with marketed brand name drugs have been required to provide a 50% discount the negotiated price for on brand name prescription drugs utilized by Medicare Part D

beneficiaries when those beneficiaries reach the coverage gap in their drug benefits, and, beginning in 2019, that discount in creased to 70%.

Since 2011, manufacturers with marketed brand name drugs have been required to provide a 50% discount the negotiated price for on brand name prescription drugs utilized by Medicare Part D beneficiaries when those beneficiaries reach the coverage gap in their drug benefits, and, beginning in 2019, that discount increased to 70%.

Drug products are subject to discounted pricing when purchased by federal agencies via the Federal Supply Schedule (FSS).

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Some countries provide that products may be marketed only after a reimbursement price has been agreed.

Some countries may require the completion of additional stu dies that compare the cost-effectiveness of a particular drug candidate to currently available therapies (so called health technology assessment, or HTA) in order to obtain reimbursement or pricing approval.

Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular drug candidate to currently available therapies (so called health technology assessment, or HTA) in order to obtain reimbursement or pricing approval.

For example, the European Union provides options for its member states to restrict the range of products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

European Union member states may approve a specific price for a product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the product on the market.

Other member states allow companies to fix their own prices for products but monitor and control prescription vol umes and issue guidance to physicians to limit prescriptions.

Recently, many countries in the European Union have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expen ditures, especially in light of the severe fiscal and debt crises experienced by many countries in the European Union.

Other member states allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.

Recently, many countries in the European Union have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the European Union.

The downward pressure on healthcare costs in general, particularly prescription drugs, has become intense.

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Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained.

Reference pricing used by va rious European Union member states, and parallel trade (arbitrage between low-priced and high-priced member states), can further reduce prices.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutic al products will allow favorable reimbursement and pricing arrangements for any of our products, if approved in those countries.

Reference pricing used by various European Union member states, and parallel trade (arbitrage between low-priced and high-priced member states), can further reduce prices.

There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any of our products, if approved in those countries.

Healthcare Law and Regulation

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the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the U.S.

Department of Health a nd Human Services, information related to payments and other transfers of value made by that entity to physicians, certain other healthcare providers, and teaching hospitals, as well as ownership and investment interests held by physicians and their immedi ate family members;

Department of Health and Human Services, information related to payments and other transfers of value made by that entity to physicians, certain other healthcare providers, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.

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In January 2013, then-President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Since its enactment, there have been numerous legal challenges and Congressional actions to repeal and replace provisions of the ACA.

Some of the provision s of the ACA have yet to be implemented, and there have been legal and political challenges to certain aspects of the ACA.

Since January 2017, President Trump has signed two executive orders and other directives designed to delay, circumvent, or loosen cer tain requirements mandated by the ACA.

District Court Judge in the Northern District of Texas, ruled that t he individual mandate is a critical and inseverable feature of the ACA, and therefore, because it was repealed as part of the Tax Act, the remaining provisions of the ACA are invalid as well.

While the Trump Administration and CMS have both stated that the ruling will have no immediate effect, it is unclear how this decision, subsequent appeals, if any, and other efforts to repeal and replace the ACA will impact the ACA and our business.

Moreover, the Bipartisan Budget Act of 2018, or the BBA, among other t hings, amends the ACA , effective January 1, 2019, to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” Congress may consider other legislation to repeal or replace additional elements of the ACA.

We continue to e valuate the effect that the ACA, the repeal of the individual mandate, and any additional repeal and replacement efforts may have on our business but expect that the ACA, as currently enacted or as it may be amended in the future, and other healthcare refo rm measures that may be adopted in the future could have a material adverse effect on our industry generally and on our ability to maintain or increase sales of our existing products that we successfully commercialize or to successfully commercialize our d rug candidates, if approved.

Since its enactment, there have been executive, legal and political challenges to certain aspects of the ACA.

For example, President Trump signed several executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the ACA.

Moreover, the Tax Cuts and Jobs Act of 2017, or the Tax Act, was enacted on December 22, 2017, and includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” Moreover, the Bipartisan Budget Act of 2018, or the BBA, among other things, amends the ACA, effective January 1, 2019, to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” On December 14, 2018, a U.S.

District Court Judge in the Northern District of Texas, ruled that the individual mandate is a critical and inseverable feature of the ACA, and therefore, because it was repealed as part of the Tax Act, the remaining provisions of the ACA are invalid as well.

Additionally, in December 2019, the U.S.

Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the ACA are invalid as well.

Supreme Court is currently reviewing this case , but it is unknown when a decision will be reached.

Although the U.S.

Supreme Court has yet ruled on the constitutionality of the ACA, on January 28, 2021, President Biden issued an

executive order to initiate a special enrollment period from February 15, 2021 through May 15, 2021 for purposes of obtaining health insurance coverage through the ACA marketplace.

The executive order also instructs certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA.

It is unclear how the Supreme Court ruling, other such litigation, and the healthcare reform measures of the Biden administration will impact the ACA and our business .

Other healthcare reform measures that may be adopted in the future could have a material adverse effect on our industry generally and on our ability to maintain or increase sales of our existing products that we successfully commercialize or to successfully commercialize our drug candidates, if approved.

In addition to the ACA, there will continue to be proposals by legislators at both the federal and state levels, regulators and third-party payors to keep healthcare costs down while expanding individual healthcare benefits.

Employees and Consultants

As of December 31, 2019, we had 23 employees, including 17 in research and development and 6 in general and administrative functions.

We also utilize 13 consultants in various roles related to our clinical study and research and development areas.

We believe our employee relations are good.

For example, there has been increasing legislative and enforcement interest in the United States with respect to drug pricing practices.

Specifically, there have been several recent presidential executive orders, Congressional inquiries, and proposed federal legislation designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs.

Human Capital Management

Cortexyme’s approach to human capital resource management starts with our mission to pioneer upstream therapeutic approaches designed to improve the lives of patients diagnosed with Alzheimer’s and other degenerative diseases.

Our industry exists in a complex regulatory environment.

The unique demands of our industry, together with the challenges of running an enterprise focused on the discovery, development, manufacture and commercialization of innovative medicines, require talent that is highly educated and/or has significant industry experience.

Additionally, for certain key functions, we require specific scientific expertise to oversee and conduct R&D activities and the complex manufacturing requirements for biopharmaceutical products.

Our base pay program aims to compensate management team and staff members relative to the value of the contributions of their role, which takes into account the skills, knowledge and abilities required to perform each position, as well as the experience brought to the job.

We also provide annual incentive programs to reward our management team and staff members in alignment with achievement of Company-wide goals that are established annually and designed to drive aspects of our strategic priorities that support and advance our strategy across our Company.

Our management team and staff members are eligible for the grant of equity awards under our long-term incentive program that are designed to align the experience of these staff with that of our shareholders.

Our management team is further incentivized through grants of performance stock option awards.

All management team and staff members also participate in a regular performance measurement process that aligns pay to performance and through which they receive performance and development feedback.

Our benefit programs are also generally broad-based, promote health and overall well-being and emphasize saving for retirement.

All management team and regular staff members are eligible to participate in the same core health and welfare and retirement savings plans.

Other employee benefits include medical plans, dental plans, vacation and sick-pay plans, employee assistance programs, flexible spending accounts, life and accident insurance and short and long-term disability benefits.

Our Compensation Committee provides oversight of our compensation plans, policies and programs.

As of December 31, 2020, we had 37 full-time employees, 1 part-time employee and 1 contractor.

Of our full-time employees, 20 of them have advanced degrees, including but not limited to Ph.D.’s, 13 work in clinical operations, 3 work in Chemistry, Manufacturing and Controls, 10 work in research and development, 11 work in, general and administration and 1 in quality assurance.

Our employees are primarily located in South San Francisco, California, however, we do have employees that work from a company leased facility in San Diego, California and others that work from their residences located across the United States.

None of our employees are represented by a labor union or are a party to a collective bargaining agreement and we believe that we have good relations with our employees.

Corporate Information

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Solely for convenience, the trademarks and trade names in this Annual Report on Form 10-K are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto.

Available Information

Available I nformation

We make available, free of charge through our website, our annual reports on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, and amendments to those reports, filed or furnished pursuant to Sections 13(a) or Section 15(d) of the Securities Exchange Act of 1934, as amended, as soon as reasonably practicable after they have been electronically filed with, or furnished to, the SEC.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business