What changed in this filing

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Item 2. Management’s Discussion and Analysis

2021-05-06 compared with 2020-11-12 · 151 added, 121 removed, 99 unchanged (73% of the section changed)

Management’s Discussion and Analysis of Financial Condition and Results of Operations.

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with (i) our unaudited condensed consolidated financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q and (ii) our audited consolidated financial statements and related notes and management’s discussion and analysis of financial condition and results of operations included in our Annual Report on Form 10-K for the year ended December 31, 2019 filed with the Securities and Exchange Commission, or the SEC, on March 16, 2020.

The following discussion and analysis of our financial condition and results of operations should be read in conjunction with (i) our unaudited condensed consolidated financial statements and related notes appearing elsewhere in this Quarterly Report on Form 10-Q and (ii) our audited financial statements and related notes and management’s discussion and analysis of financial condition and results of operations included in our Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission (the “SEC”), on March 1, 2021.

Unless the context requires otherwise, references in this Quarterly Report on Form 10-Q to the “Company,” “Cortexyme,” “we,” “us” and “our” refer to Cortexyme, Inc.

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Forward-Looking Statements

This Quarterly Report on Form 10-Q contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act.

All statements other than statements of historical facts contained in this quarterly report, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations, adequacy of our cash resources and working capital, impact of COVID-19 pandemic on our research and development activities and business operations, and future results of anticipated products, are forward-looking statements.

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Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

We are a clinical-stage biopharmaceutical company pioneering a novel disease-modifying therapeutic approach to treat what we believe to be a key underlying cause of Alzheimer’s and other degenerative diseases.

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.

We are a clinical stage biopharmaceutical company advancing a pivotal trial in Alzheimer's disease with topline data expected in the fourth quarter of 2021 and a growing pipeline of therapeutics for degenerative diseases.

Our approach is based on the seminal discovery of the presence of Porphyromonas gingivalis (“P.

gingivalis”) , and its secreted toxic virulence factor proteases, called gingipains, in the brains of greater than 90% of Alzheimer’s 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 initiated a global 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 in April 2019 in the United States and in September 2019 in Europe.

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 24 weeks of treatment and expect top-line results by the end of 2021.

In November 2020, final enrollment in the GAIN Trial was 643 participants.

The GAIN Trial also includes an open-label extension (OLE) in the United States that began dosing patients in April 2020.

Upon completing the 48-week placebo-controlled period of the GAIN Trial, participants in the GAIN Trial’s placebo and active arms in the U.S.

may be eligible to enroll in the OLE study, where they will receive 40 mg or 80 mg of atuzaginstat twice daily for an additional 48 weeks.

The OLE is intended to evaluate long-term safety and efficacy measures of participants in the GAIN Trial.

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.

A substudy of the GAIN trial, called REPAIR, will also report in Q4 2021 on the efficacy of atuzaginstat in periodontal disease.

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 IND enabling studies are proceeding to expectations and a first-in-human study is expected to begin in Q3 2021 and will initially be positioned in periodontal disease with potential efficacy in multiple indications.

Two arginine gingipain inhibitors, COR788 and COR822, have been selected as lead compounds to progress toward IND-enabling studies, including manufacturing scale-up and dose range-finding toxicology studies based on their properties of potency, selectivity, pharmacologic efficacy, and pharmacokinetics.

Arginine gingipain is a distinct target associated with P.

gingivalis that contributes to bacterial survival, replication and toxicity.

An arginine gingipain inhibitor may be used as monotherapy in new indications or potentially additively with lysine gingipain inhibitors, like atuzaginstat.

Both molecules have novel composition of matter (patent pending), are brain penetrant and orally available.

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.

The disease afflicts an estimated 5.7 million people in the United States and more than 30 million people worldwide and is expected to grow to 14.0 million people in the United States by 2050.

The direct costs of caring for individuals with Alzheimer’s disease and other dementias in the United States were estimated to total $300 billion in 2020 and are projected to increase to $1.1 trillion by 2050, according to the Alzheimer’s Association.

Historical challenges in developing effective therapeutics for this disease include a poor understanding of disease causation and animal models that do not translate to efficacy in humans.

We believe our novel approach can overcome these challenges by targeting an upstream cause of neuroinflammation and neurodegeneration.

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.

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 Parkinson’s disease called the PEAK (Gingipain inhibitor for treatment of PArKinson’s’ 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 we 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 our 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 GAIN trial by the FDA.

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

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

Business Update Regarding COVID-19

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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.

To date, our employees, vendors and clinical trial sites have been able to advance our GAIN clinical trial and complete enrollment.

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.

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.

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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.

The Company has 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 approximately an additional 70 subjects in the GAIN trial.

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 an additional 7 3 subjects in the GAIN trial.

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

The Company will continue to monitor the COVID-19 situation and its impact on the ability to continue the development of, and seek regulatory approvals for, the Company’s 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.

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.

Financial Overview

Since commencing material operations in 2014, we have devoted substantially all of our efforts and financial resources to building our research and development capabilities, establishing our corporate infrastructure and most recently, executing our Phase 1a, Phase 1b and Phase 2/3 clinical trials of atuzaginstat.

We are expecting top line data from GAIN Phase 2/3 trial in Q4 2021 and increasing investment in new indications for atuzaginstat and clinical trials for COR588.

To date, we have not generated any revenue and we have never been profitable.

We have incurred net losses since the commencement of our operations.

As of March 31, 2021, we had an accumulated deficit of $169.7 million.

We incurred a net loss of $23.1 million in the three months ended March 31, 2021.

We do not expect to generate product revenue unless and until we obtain marketing approval for and commercialize a drug candidate, and we cannot assure you that we will ever generate significant revenue or profits.

To date, we have financed our operations primarily through the issuance and sale of convertible promissory notes and redeemable convertible preferred stock and common stock.

From inception through March 31, 2021, we received net proceeds of approximately $294.9 million from the issuance of redeemable convertible preferred stock, convertible promissory notes and common stock.

This includes net proceeds of approximately $117.6 million from the issuance and sale of common stock in a private placement to certain accredited investors received in February 2020.

As of March 31, 2021 and December 31, 2020, we had cash, cash equivalents and short-term investments of $147.0 million and $133.8 million, respectively.

The balances exclude long-term investments of $23.7 million and $50.5 million as of those same periods.

Our cash equivalents, short-term and long-term investments are held in money market funds, certificate of deposits, repurchase agreements, investments in corporate debt securities, municipal debt obligations and government agency obligations.

We believe that our existing cash, cash equivalents and investments will be sufficient to fund our planned operations through 2023.

We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.

We expect to incur substantial expenditures in the foreseeable future as we expand our pipeline and advance our drug candidates through clinical development, the regulatory approval process and, if approved, commercial launch activities.

Specifically, in the near term we expect to incur substantial expenses relating to our ongoing and planned clinical trials, the development and validation of our manufacturing processes, and other development activities.

We will need substantial additional funding to support our continuing operations and pursue our development strategy.

Until such time as we can generate significant revenue from sales of an approved drug, if ever, we expect to finance our operations through the sale of equity, debt financings or other capital sources.

Adequate funding may not be available to us on acceptable terms, or at all.

If we fail to raise capital or enter into such agreements as, and when, needed, we may have to significantly delay, scale back or discontinue the development and commercialization of our drug candidates or delay our efforts to expand our product pipeline.

Critical Accounting Policies and Significant Judgments and Estimates

Our management’s discussion and analysis of our financial condition and results of operations is based on our consolidated financial statements, which have been prepared in accordance with U.S.

generally accepted accounting principles (“GAAP”).

preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods.

Our estimates are based on our historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources.

Actual results may differ from these estimates under different assumptions or conditions.

We believe that the assumptions and estimates associated with accrued research and development expenditures and stock-based compensation have the most significant impact on our condensed consolidated financial statements.

Therefore, we consider these to be our critical accounting policies and estimates.

The following critical accounting policies are described under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies, Significant Judgements and Use Estimates” in our 2020 Annual Report on Form 10-K and the notes to the unaudited condensed consolidated financial statements included in Item 1, “Unaudited Financial Statements,” of this Quarterly Report on Form 10-Q.

We believe that of our critical accounting policies, the following accounting policies are the most critical to fully understanding and evaluating our financial condition and results of operations:

Research and Development Expenses;

Stock-Based Compensation Expense;

There have been no material changes in our critical accounting policies during the three months ended March 31, 2021, as compared to those disclosed in “Management’s Discussion and Analysis of Financial Condition and Results of Operations — Critical Accounting Policies, Significant Judgments and Use of Estimates” in our Annual Report.

Components of Results of Operations

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Non-refundable advance payments and deposits for services that will be used or rendered for future research and development activities are recorded as prepaid expenses and recognized as an expense as the related services are performed.

To date, substantially all of our research and development expenses have supported the advancement of atuzaginstat and our other drug candidates are in preclinical development.

To date, our research and development expenses have supported the advancement of atuzaginstat and our other drug candidates in preclinical development.

As a result, we do not allocate our costs to individual drug candidates.

We expect that at least for the foreseeable future, a substantial majority of our research and development expense will support the clinical and regulatory development of atuzaginstat.

We expect our research and development expenses to increase substantially during the next few years as we seek to complete existing and initiate additional clinical trials, pursue regulatory approval of atuzaginstat and advance other drug candidates into preclinical and clinical development.

Over the next few years, we expect our preclinical, clinical and contract manufacturing expenses to increase significantly relative to what we have incurred to date.

Predicting the timing or the final cost to complete our clinical program or validation of our manufacturing and supply processes is difficult and delays may occur because of many factors.

We initiated a global Phase 2/3 clinical trial of atuzaginstat, called the GAIN trial, in mild to moderate Alzheimer’s patients in April 2019 in the United States and in September 2019 in Europe.

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 24 weeks of treatment and expect top-line results by the

In November 2020, final enrollment in the GAIN Trial was 64 3 participants.

Patients successfully completing the 48-week placebo-controlled period of the GAIN tri al are eligible to participate in the open-label extension (OLE) in the United States.

We started dosing patients in the OLE starting in April 2020 where they receive 40 mg or 80 mg of atuzaginstat twice daily for an additional 48 weeks.

The OLE is intended to evaluate the long-term safety and efficacy measures of participants in the GAIN trial.

The duration, costs and timing of our clinical trial and development of our product candidates will depend on a variety of factors that include, but are not limited to, the following:

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the efficacy and safety profile of the product candidates.

Because our product candidate is in clinical development and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidate or whether, or when, we may achieve profitability.

Because our product candidate is still in clinical development and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidate or whether, or when, we may achieve profitability.

The COVID-19 pandemic may have an adverse impact on our operations, supply chains, our current or future clinical trials, and increase our expenses, including as a result of impacts associated with preventive and precautionary measures that we, other businesses and governments are taking.

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General and administrative expenses consist principally of personnel-related costs, including payroll and stock-based compensation, for personnel in executive, finance, human resources, business and corporate development, and other administrative functions, professional fees for legal, consulting, insurance and accounting services, allocated rent and other facilities costs, depreciation, and other general operating expenses not otherwise classified as research and development expenses.

We anticipate that our general and administrative expenses will continue to increase as a result of staff expansion and additional occupancy costs, as well as costs associated with being a public company, including higher legal and accounting fees, investor relations costs, higher insurance premiums and other compliance costs associated with being a public company.

We anticipate that our general and administrative expenses will increase as the size of our business operations grows to support additional research and development activities.

Interest Income

Interest income consists of interest earned on our cash equivalents and investments recognized during the period.

Interest and other income, net consists primarily of interest earned on our short-term and long-term investments portfolio.

Results of Operations

Three Months Ended September 30, 2020 and 2019

The following sets forth our results of operations for the three months ended September 30, 2020 and 2019 (in thousands):

Three Months Ended September 30,

Operating expenses:

Research and development

General and administrative

Loss from operations

Interest income

Research and Development Expenses (in thousands)

Three Months Ended September 30,

Direct research and development expenses:

Atuzaginstat (COR388)

Other direct research costs

Indirect research and development expenses:

Personnel related (including stock-based compensation)

Facilities and other research and development expenses

Total research and development expenses

Research and development expenses were $17.0 million for the three months ended September 30, 2020, compared to $8.3 million for the three months ended September 30, 2019.

The increase of $8.7 million was driven primarily by increasing patient enrollments in the GAIN trial resulting in increases of $3.4 million in clinical trial expenses for our lead product candidate, atuzaginstat which entered into Phase 2/3 clinical trials in 2019, $2.9 million in drug manufacturing costs to support the clinical trial and $0.4 million in non-clinical related costs.

We experienced a net increase of $1.8 million in personnel related expenses primarily due to an increase in our employee headcount which was comprised of an increase in compensation and benefit costs of $0.5 million and $1.3 million in stock-based compensation costs.

Allocated facilities and other non-clinical research not related to atuzaginstat increased $0.2 million for the period.

General and Administrative Expenses

General and administrative expenses increased $2.6 million to $4.9 million for the three months ended September 30, 2020 from $2.3 million for three months ended September 30, 2019 primarily due to an increase in personnel costs due to an increase in our employee headcount which was comprised of an increase in compensation and benefits costs of $0.5 million and $2.0 million in stock-based compensation expense and $0.1 million increase in costs associated with being a public company.

Interest Income

Interest income was $0.4 million for the three months ended September 30, 2020 compared to $0.7 million for the three months ended September 30, 2019.

The decrease was a result of lower yields on our available for sale portfolio from the prior year.

We anticipate overall yields from our investment portfolio will remain at historic lows in future quarters due to the impact of the COVID-19 pandemic on the financial markets, specifically the credit securities markets.

Nine Months Ended September 30, 2020 and 2019

The following sets forth our results of operations for the nine months ende d September 30, 2020 and 2019 (in thousands):

Nine Months Ended September 30,

Comparison of the three months ended March 31, 2021 to the three months ended March 31, 2020

The following sets forth our results of operations for the three months ended March 31, 2021 and 2020 (in thousands):

Three Months Ended March 31,

Operating expenses:

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Research and Development Expenses (in thousands):

Nine Months Ended September 30,

Three Months Ended March 31,

Direct research and development expenses:

Atuzaginstat (COR388)

Other direct research costs

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Total research and development expenses

Research and development expenses were $45.4 million for the nine months ended September 30, 2020, compared to $20.2 million for the nine months ended September 30, 2019.

The increase of $25.3 million was driven mostly by increasing patient enrollments in the GAIN trial resulting in $11.3 million in clinical trial expenses for our lead product candidate, atuzaginstat which entered into Phase 2/3 clinical trials in 2019, $6.0 million in drug manufacturing costs to support the clinical trial and $1.6 million in non-clinical related costs.

We also experienced a net increase of $5.9 million in personnel related expenses due to an increase in our employee headcount which was comprised of an increase in compensation and benefit costs of $2.1 million and $3.8 million in stock-based compensation costs.

Additionally, allocated facility costs and other non-clinical costs increased $0.4 million due primarily to pipeline research.

Research and development expenses were $16.8 million for the three months ended March 31, 2021, compared to $14.4 million for the three months ended March 31, 2020, an increase of $2.4 million.

The costs for atuzaginstat, currently in our GAIN Phase 2/3 clinical trial decreased $2.7 million from the prior year due to decreases of $1.7 million in drug manufacturing costs and $1.0 million in clinical trial costs.

The GAIN trial is expected to conclude in the fourth quarter 2021 and we anticipate continued overall expenses to decrease as patients complete the trial protocols and the final top-line data read out occurs.

In the quarter ended March 31, 2021, the company started IND enabling studies for a new compound COR588.

COR588 is a unique small molecule lysine gingipain inhibitor with likely once daily oral dosing that we intend to position in periodontal disease and other new indications.

We incurred $1.4 million in costs for these initial IND enabling studies and expect increased costs for this compound as it moves to a Phase 1 clinical study anticipated to begin in the third quarter 2021.

We also incurred increases of $3.6 million in personnel related expenses due to a $1.0 million increase in personnel related expenses for increased headcount and a $2.6 million increase in allocated stock-based compensation costs.

General and Administrative Expenses

General and administrative expenses increased approximately $6.6 million to $12.6 million for the nine months ended September 30, 2020 from $6.0 million for the nine months ended September 30, 2019.

The increase in general and administrative expenses was primarily due to an increase of $5.6 million in personnel costs due to an increase in our employee headcount which was comprised of an increase in compensation and benefits costs of $1.4 million and $4.2 million in stock-based compensation expense and increases in $1.0 million in insurance expense associated with becoming a public company.

General and administrative expenses increased $3.0 million to $6.5 million for the three months ended March 31, 2021 from $3.5 million for three months ended March 31, 2020.

The increase in general and administrative expenses was primarily due to an increase of $2.9 million due to an increase in our employee headcount which was comprised of an increase in compensation and benefits costs of $0.5 million and $2.4 million in allocated stock-based compensation expense.

Interest Income

Interest income was $1.7 million for the nine months ended September 30, 2020 compared to $1.6 million for the nine months ended September 30, 2019.

The increase was a result of increased average cash and investment balances of approximately $70.0 million from the proceeds of private placement which closed in February 2020.

This was offset by significantly lower yields on the portfolio from the previous year.

Interest income was $0.2 million for the three months ended March 31, 2021 compared to $0.7 million for the three months ended March 31, 2020.

The decrease was a result of decreased average cash and investment balances and decreases in the overall yield of the investment portfolio.

We anticipate continued historic low overall yields from our investment portfolio in future quarters due to the impact of the COVID-19 pandemic on the financial markets, specifically the credit securities markets.

Liquidity, Capital Resources and Plan of Operations

We have incurred cumulative net losses and negative cash flows from operations since our inception and anticipate we will continue to incur net losses for the foreseeable future.

As of September 30, 2020, we had an accumulated deficit of $126.1 million and had cash, cash equivalents and short-term investments of $137.8 million.

Based on our current cash requirements, we believe that we will continue to be able to hold all securities to their final maturity and not realize material gains or losses in the available for sale portfolios.

Based on our existing business plan, we believe that our existing cash, cash equivalents, and short-term investments will be sufficient to fund our anticipated level of operations for a period of at least one year from the date this Quarterly Report on Form 10-Q is filed with the Securities and Exchange Commission.

As of March 31, 2021, we had an accumulated deficit of $169.7 million.

As of March 31, 2021, we had cash, cash equivalents and investments of $170.8 million.

Based on our existing business plan, we believe that our existing cash, cash equivalents and investments will be sufficient to fund our anticipated level of operations through at least 2023.

Capital Resources

Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures related to our Phase 2/3 drug candidate, atuzaginstat, research on our proprietary library of small molecules, additional pipeline candidates and other research efforts, and to a lesser extent, general and administrative expenditures.

Our primary use of cash is to fund operating expenses, which consist primarily of research and development expenditures related to our lead program, atuzaginstat, and other research efforts, and to a lesser extent, general and administrative expenditures.

Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable and accrued expenses.

Our lead product candidate is in the early stages of clinical development and the outcome of these efforts is uncertain.

Our product candidate is still in clinical development and the outcome of these efforts is uncertain.

Accordingly, we cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidates or whether, or when, we may achieve profitability.

Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity or debt financings and collaboration arrangements.

If we do raise additional capital through public or private equity offerings, the ownership interest of our existing stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our stockholders’ rights.

If we raise additional capital through debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

If we are unable to raise capital when needed, we will need to delay, reduce or terminate planned activities to reduce costs.

Doing so will likely harm our ability to execute our business plans.

We may also be required to sell or license to others rights to our drug candidate in certain territories or indications that we would prefer to develop and commercialize ourselves.

We completed an initial public offering;

or the IPO in May 2019 by issuing and selling 5,073,800 shares of common stock at a public offering price of $17.00 per share, including 661,800 shares sold pursuant to the underwriters’ full exercise of their option to purchase additional shares.

The aggregate net proceeds received by us from the offering, net of underwriting discounts and commissions and offering expenses, was approximately $77.8 million.

Upon the closing of the IPO, all of the outstanding shares of redeemable convertible preferred stock automatically converted into 18,161,027 shares of common stock.

Subsequent to the closing of the IPO, there were no shares of redeemable convertible preferred stock outstanding.

In February 2020, we completed a private placement by issuing and selling 2,500,000 shares at $50.00 per share.

The aggregate net proceeds received by us from the offering net of offering expenses, was approximately $117.6 million.

We will continue to require additional capital to develop our drug candidates and fund operations for the foreseeable future.

We may seek to raise capital through private or public equity or debt financings, collaborative or other arrangements with other companies, or through other sources of financing.

Adequate additional funding may not be available to us on acceptable terms or at all.

Our failure to raise capital as and when needed could have a negative impact on our financial condition and our ability to pursue our business strategies.

We anticipate that we will need to raise substantial additional capital, the requirements of which will depend on many factors, including:

the progress, costs, trial design, results of and timing of our Phase 2/3 GAIN trial and other clinical trials of atuzaginstat, including our Phase 2 PEAK trial for Parkinson’s disease and for potential additional indications that we may pursue beyond Alzheimer’s and Parkinson’s disease;

the willingness of the FDA or EMA to accept our Phase 2/3 GAIN trial, as well as data from our completed and planned clinical and preclinical studies and other work, as the basis for review and approval of atuzaginstat for Alzheimer’s disease;

the outcome, costs and timing of seeking and obtaining FDA, EMA and any other regulatory approvals;

the number and characteristics of drug candidates that we pursue;

our ability to manufacture sufficient quantities of our drug candidates;

our need to expand our research and development activities;

the costs associated with securing and establishing commercialization and manufacturing capabilities;

the costs of acquiring, licensing or investing in businesses, drug candidates and technologies;

our ability to maintain, expand and defend the scope of our intellectual property portfolio, including the amount and timing of any payments we may be required to make, or that we may receive, in connection with the licensing, filing, prosecution, defense and enforcement of any patents or other intellectual property rights;

our need and ability to retain management and hire scientific and clinical personnel;

the effect of competing drugs and drug candidates and other market developments;

our need to implement additional internal systems and infrastructure, including financial and reporting systems;

the economic and other terms, timing of and success of any collaboration, licensing or other arrangements into which we may enter in the future.

If we raise additional funds by issuing equity securities, our stockholders will experience dilution.

Any future debt financing into which we enter may impose upon us additional covenants that restrict our operations, including limitations on our ability to incur liens or additional debt, pay dividends, repurchase our common stock, make certain investments and engage in certain merger, consolidation or asset sale transactions.

Any debt financing or additional equity that we raise may contain terms that are not favorable to us or our stockholders.

If we are unable to raise additional funds when needed, we may be required to delay, reduce, or terminate some or all of our development programs and clinical trials.

We may also be required to sell or license to others rights to our drug candidates in certain territories or indications that we would prefer to develop and commercialize ourselves.

Our ability to raise additional capital may be adversely impacted by potential worsening global economic conditions and the recent disruptions to, and volatility in, the credit and financial markets in the United States and worldwide resulting from the ongoing COVID-19 pandemic.

However, based on our current business plans, we believe that our existing cash, cash equivalents and investments will be sufficient to fund our planned operations through 2022, including through the completion and the announcement of the top-line results of our Phase 2/3 GAIN trial.

However, based on our current business plans, w e believe that our existing cash, cash equivalents and investments will be sufficient to fund our planned operations through 2023, including through the completion and the announcement of the top-line results of our Phase 2/3 GAIN trial.

Summary Statement of Cash Flows

The following table sets forth the primary sources and uses of cash and cash equivalents for each of the periods presented below (in thousands):

Nine Months Ended September 30,

Three Months Ended March 31,

Net cash (used in) provided by:

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Operating Activities

Net cash used in operating activities was $37.5 million for the nine months ended September 30, 2020.

Cash used in operating activities was primarily due to our net loss of $56.3 million for the period, adjusted for $10.5 million of non-cash items, including $9.5 million in stock-based compensation and a net increase in accounts payable, accrued expenses and other current liabilities of $7.3 million and decreases in our current assets of $1.0 million.

Net cash used in operating activities was $22.3 million for the nine months ended September 30, 2019 and was primarily due to our net loss for the period of $24.6 million, and also due to use of cash in for prepaid expenses and other assets of $3.5 million offset by cash provided by increases in our accounts payable and accrued expenses of $4.7 million related to the activities surrounding our Phase 2/3 clinical trial.

Non-cash operating income and expenses (net) accounted for $1.1 million of the net loss.

Net cash used in operating activities was $13.6 million for the three months ended March 31, 2021.

Cash used in operating activities was primarily due to our net loss of $23.1 million for the period, adjusted for $7.4 million of non-cash items, including $7.0 million in stock-based compensation and a net decrease in prepaid expenses and other assets of $1.2 million and a net increase in accounts payable, accrued expenses and other current liabilities of $0.9 million.

Net cash used in operating activities was $10.8 million for the three months ended March 31, 2020.

Cash used in operating activities was primarily due to our net loss of $17.2 million for the period, adjusted for $2.2 million of non-cash items, including $2.0 million in stock-based compensation and a net increase in accounts payable, accrued expenses and other current liabilities of $4.2 million.

Investing Activities

Cash used in investing activities was $68.3 million for the nine months ended September 30, 2020, primarily related to the purchase of available for sale investment securities of $183.4 million and maturities of $115.1 million.

Cash used in investing activities was $35.5 million in the nine months ended September 30, 2019, primarily related to the purchase of available for sale investment securities of $98.5 million and maturities of $63.0 million.

Cash provided by investing activities was $31.6 million in the three months ended March 31, 2021, primarily related to the purchase of investments of $12.0 million, and maturities of short-term investments of $43.6 million.

Cash used by investing activities was $72.7 million for the three months ended March 31, 2020, primarily related to the purchase of available for sale investment securities with the proceeds from the private placement transaction which closed in February 2020.

Financing Activities

Cash provided by financing activities was $118.8 million for the nine months ended September 30, 2020, which consisted primarily of net proceeds from the private placement transaction and the proceeds from the exercise of stock options.

Cash provided by financing activities was $77.9 million in the nine months ended September 30, 2019, which consisted primarily of net proceeds from the initial public offering in the period.

Cash provided by financing activities was $0.4 million in the three months ended March 31, 2021, which consisted of net proceeds from the exercise of stock options in the period.

Cash provided by financing activities was $117.9 million for the three months ended March 31, 2020, which consisted primarily of net proceeds from the private placement transaction and the proceeds from the exercise of stock options.

Contractual Obligations and Commitments

There have been no material changes to our contractual obligations and other commitments as of September 30, 2020, as compared to those disclosed in our Annual Report on Form 10-K.

There have been no material changes to our contractual obligations and other commitments as of March 31, 2021, as compared to those disclosed in our Annual Report on Form 10-K.

Our contractual obligations primarily consist of our obligations under non-cancellable operating leases and other purchase obligations.

We enter into contracts in the normal course of business with third party contract organizations for clinical trials, non-clinical studies and testing, manufacturing, and other services and products for operating purposes.

The amount and timing of the payments under these contracts varies based upon the timing of the services.

We have recorded accrued expense of approximately $13.2 million in our condensed consolidated balance sheet for expenditures incurred by these vendors as of March 31, 2021.

We have approximately $11.1 million in cancellable future commitments based on existing contracts as of March 31, 2021.

Off-Balance Sheet Arrangements

We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined under the rules and regulations of the SEC.

As an emerging growth company under the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, we can take advantage of an extended transition period for complying with new or revised accounting standards.

This allows an emerging growth company to delay the adoption of certain accounting standards until those standards would otherwise apply to private companies.

We have irrevocably elected not to avail ourselves of this exemption and, therefore, we will be subject to the same new or revised accounting standards as other public companies that are not emerging growth companies.

We intend to rely on other exemptions provided by the JOBS Act, including without limitation, not being required to comply with the auditor attestation requirements of Section 404(b) of Sarbanes-Oxley.

We will remain an emerging growth company until December 31, 2020.

Critical Accounting Policies, Significant Judgments and Use of Estimates

Our management’s discussion and analysis of our financial condition and results of operations is based on our condensed financial statements, which have been prepared in accordance with United States generally accepted accounting principles.

The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements, as well as the reported expenses incurred during the reporting periods.

Actual results may differ from these estimates under different assumptions or conditions.

Therefore, we consider these to be our critical accounting policies and estimates.

The following critical accounting policies are described under the heading “Management’s Discussion and Analysis of Financial Condition and Results of Operations—Critical Accounting Policies, Significant Judgements and Use Estimates” in our 2019 Annual Report on Form 10-K and the notes to the unaudited condensed financial statements included in Item 1, “Unaudited Financial Statements,” of this Quarterly Report on Form 10-Q.

We believe that of our critical accounting policies, the following accounting policies are the most critical to fully understanding and evaluating our financial condition and results of operations:

Research and Development Expenses;

Stock-Based Compensation Expense;

Recent Accounting Pronouncements

Please refer to Note 2 to our unaudited condensed financial statements appearing under Part 1, Item 1 of this report for a discussion of new accounting standards updates that may impact us.

Please refer to Note 2 to our unaudited condensed consolidated financial statements appearing under Part 1, Item 1 of this report for a discussion of new accounting standards updates that may impact us.

Available information

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The content on any website referred to in this Quarterly Report on Form 10-Q is not incorporated by reference in this Form 10-Q unless expressly noted.

Further, the Company’s references to website URLs are intended to be inactive textual references only.

Further, references to website URLs are intended to be inactive textual references only.

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-Q

Item 2. Management’s Discussion and Analysis