| PROSPECTUS SUPPLEMENT |
Filed Pursuant to Rule 424(b)(5) |
| (To Prospectus Dated September 24, 2021) |
Registration No. 333-259788 |
Anavex Life Sciences Corp.
Up to $150,000,000 of Common Stock and
Up to 150,000 Shares of Common Stock as Commitment
Shares
This prospectus supplement relates to the issuance
and sale of up to $150,000,000 in shares of our common stock (the “Purchase Shares”) and up to an additional 150,000
shares of our common stock issued as commitment shares to Lincoln Park Capital Fund, LLC, or Lincoln Park, from time to time, in
one or more transactions in amounts, at prices, and on terms that will be determined at the time these securities are offered pursuant
to a purchase agreement between us and Lincoln Park, dated February 3, 2023, (the “Purchase Agreement”), whereby Lincoln
Park committed to purchase up to $150,000,000 of our common stock, and we have agreed to issue (i) 75,000 shares of common stock
on the date of filing of this prospectus supplement (the “Initial Commitment Shares”) and (ii) up to 75,000 shares
of common stock pro-rata as up to $150,000,000 of shares of our common stock are purchased by Lincoln Park at our discretion from
time to time, in accordance with the Purchase Agreement (the “Additional Commitment Shares”, and together with the
Initial Commitment Shares, the “Commitment Shares”). See the Section herein entitled “The Lincoln Park Transaction”
for a description of the Purchase Agreement. Lincoln Park is an “underwriter” within the meaning of Section 2(a)(11)
of the Securities Act of 1933, as amended (the “Securities Act”).
Our common stock is currently listed on the Nasdaq
Capital Market under the symbol “AVXL”. On February 3, 2023 the last reported sale price of our common stock was $11.26 per
share.
We will pay the expenses incurred in registering the
shares, including legal and accounting fees. See “Plan of Distribution”.
Investing in our securities involves a high degree
of risk. See the Section entitled “Risk Factors” on page S-6 of this prospectus supplement and the Section entitled “Risk
Factors” beginning on page 11 of the accompanying prospectus, and in the documents we filed with the Securities and Exchange Commission
that are incorporated in this prospectus supplement by reference for certain risks and uncertainties you should consider.
Neither the Securities and Exchange Commission
nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus.
Any representation to the contrary is a criminal offense.
The date of this prospectus supplement is February
3, 2023.
TABLE OF CONTENTS
PROSPECTUS SUPPLEMENT
PROSPECTUS
ABOUT THIS PROSPECTUS SUPPLEMENT
This
prospectus supplement and the accompanying prospectus are part of a registration statement on Form S-3 (File No. 333-259788) that
we filed with the Securities and Exchange Commission, or SEC, and that became automatically effective on September 24, 2021. This
document is in two parts. The first part is this prospectus supplement, which describes the terms of this offering of common stock
and adds, updates and changes information contained in the accompanying prospectus and the documents incorporated herein by reference.
The second part is the prospectus, which gives more general information, some of which may not apply to this offering of common
stock. If the information contained in this prospectus supplement differs or varies from the information contained in the accompanying
prospectus or any document incorporated herein by reference, you should rely on the information in this prospectus supplement.
Before investing in our common stock, you should read this prospectus supplement and the accompanying prospectus, as well as the
additional information incorporated by reference herein described under “Incorporation by Reference” on page S-14
of this prospectus supplement.
We have not and Lincoln Park has not authorized
anyone to provide you with any information or to make any representation, other than those contained or incorporated by reference
in this prospectus supplement and the accompanying prospectus or in any free writing prospectus we have prepared and to which we
have referred you. We take no responsibility for, and provide no assurance as to the reliability of, any other information that
others may give you. Neither we nor Lincoln Park are making an offer to sell or soliciting an offer to buy our securities in any
jurisdiction where an offer or solicitation is not authorized or in which the person making that offer or solicitation is not qualified
to do so or to anyone to whom it is unlawful to make an offer or solicitation. You should assume that the information appearing
in this prospectus supplement, the accompanying prospectus, the documents incorporated by reference into this prospectus supplement
and the accompanying prospectus, and in any free writing prospectus that we may authorize for use in connection with this offering,
is accurate only as of the date of those respective documents. Our business, financial condition, results of operations and prospects
may have changed since those dates.
We are not, and Lincoln Park is not, making
an offer or sale of our common stock in any jurisdiction where such offer or sale is not permitted.
The information in this prospectus supplement
is not complete. You should carefully read this prospectus supplement and the accompanying base prospectus, including the information
incorporated by reference herein and therein, before you invest, as these documents contain information you should consider when
making your investment decision.
None of Anavex Life Sciences Corp., Lincoln
Park or any of their representatives are making any representation to you regarding the legality of an investment in our common
stock by you under applicable laws. You should consult with your own advisors as to legal, tax, business, financial and related
aspects of an investment in our common stock.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING
STATEMENTS
This prospectus supplement contains forward-looking
statements. All statements other than statements of historical facts contained in this prospectus supplement, including statements
regarding our anticipated future clinical and regulatory milestone events, future financial position, business strategy and plans
and objectives of management for future operations, are forward-looking statements. The words “believe,” “may,”
“estimate,” “continue,” “anticipate,” “intend,” “expect,” “should,”
“forecast,” “could,” “suggest,” “plan,” and similar expressions, as they relate
to us, are intended to identify forward-looking statements. Such forward-looking statements include, without limitation, statements
regarding:
| ● | volatility in our stock price and in the markets in general; |
| ● | our ability to conduct preclinical studies and clinical trials for our product candidates; |
| ● | our ability to raise additional capital on favorable terms and the impact of such activities on
our stockholders and stock price; |
| ● | the impact of the COVID-19 outbreak and its effect on us; |
| ● | our ability to generate any revenue or to continue as a going concern; |
| ● | our ability to execute our development plan on time and on budget; |
| ● | our products’ ability to demonstrate efficacy or an acceptable safety profile; |
| ● | our ability to obtain the support of qualified scientific collaborators; |
| ● | our ability, whether alone or with commercial partners, to successfully commercialize any of our
product candidates that may be approved for sale; |
| ● | our ability to identify and obtain additional product candidates; |
| ● | our reliance on third parties in non-clinical studies and clinical trials; |
| ● | our ability to defend against product liability claims; |
| ● | our ability to safeguard against security breaches; |
| ● | our ability to obtain and maintain sufficient intellectual property protection for our product
candidates; |
| ● | our ability to comply with our intellectual property licensing agreements; |
| ● | our ability to defend against claims of intellectual property infringement; |
| ● | our ability to comply with the maintenance requirements of the government patent agencies; |
| ● | our ability to protect our intellectual property rights throughout the world; |
| ● | the anticipated start dates, durations and completion dates of our ongoing and future clinical
studies; |
| ● | the anticipated designs of our future clinical studies; |
| ● | our anticipated future regulatory submissions and our ability to receive regulatory approvals to
develop and market our product candidates, including any orphan drug or Fast Track designations; and |
| ● | our anticipated future cash position and ability to obtain funding for our operation. |
We have based these forward-looking statements
largely on our current expectations and projections about future events, including the responses we expect from the U.S. Food and
Drug Administration, or FDA, and other regulatory authorities and financial trends that we believe may affect our financial condition,
results of operations, business strategy, preclinical and clinical trials and financial needs. These forward-looking statements
are subject to a number of risks, uncertainties and assumptions including without limitation the risks described in “Risk
Factors” in “Part I, Item 1A” of our Annual Report on Form 10-K for the fiscal year ended September 30, 2022
and our subsequent quarterly reports on Form 10-Q. These risks are not exhaustive. We operate in a very competitive and rapidly
changing environment. New risk factors emerge from time to time and it is not possible for our management to predict all risk factors,
nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause
actual results to differ materially from those contained in any forward-looking statements. You should not rely upon forward-looking
statements as predictions of future events. We cannot assure you that the events and circumstances reflected in the forward-looking
statements will be achieved or occur and actual results could differ materially from those projected in the forward-looking statements.
Except as required by applicable laws including the securities laws of the United States, we assume no obligation to update or
supplement forward-looking statements.
PROSPECTUS
SUPPLEMENT SUMMARY
This summary highlights information contained
elsewhere in this prospectus supplement and the accompanying base prospectus. It does not contain all of the information that you
should consider before making an investment decision. You should read this entire prospectus supplement, the accompanying base
prospectus and the documents incorporated herein by reference for a more complete understanding of this offering of common stock.
Please read “Risk Factors” in our Annual Report on Form 10-K for the fiscal year ended September 30, 2022 for information
regarding risks you should consider before investing in our common stock.
Throughout this prospectus supplement,
when we use the terms “Anavex,” “we,” “us,” “our” or the “Company,”
we are referring either to Anavex Life Sciences Corp. in its individual capacity or to Anavex Life Sciences Corp. and its operating
subsidiaries collectively, as the context requires.
Our Company
Overview
Anavex Life Sciences Corp. is a clinical stage
biopharmaceutical company engaged in the development of differentiated therapeutics by applying precision medicine to central nervous
system (“CNS”) diseases with high unmet need. We analyze genomic data from clinical trials to identify biomarkers,
which we use in the analysis of our clinical trials.
Our lead product candidate, ANAVEX®2-73,
is being developed to treat Alzheimer’s disease, Parkinson’s disease and potentially other central nervous system diseases,
including rare diseases, such as Rett syndrome, a rare severe neurological monogenic disorder caused by mutations in the X-linked
gene, methyl-CpG-binding protein 2 (“MECP2”).
We currently have two core programs and two
seed programs. Our core programs are at various stages of clinical and preclinical development, in neurodegenerative and neurodevelopmental
diseases.
Clinical Trials Overview
Alzheimer’s Disease
In November 2016, we completed a Phase 2a clinical
trial, consisting of Part A and Part B, which lasted a total of 57 weeks, for ANAVEX®2-73 in mild-to-moderate Alzheimer’s
patients. This open-label randomized trial in Australia met both primary and secondary endpoints and was designed to assess the
safety and exploratory efficacy of ANAVEX®2-73 in 32 patients. ANAVEX®2-73 targets sigma-1 and muscarinic
receptors, which have been shown in preclinical studies to reduce stress levels in the brain believed to restore cellular homeostasis
and to reverse the pathological hallmarks observed in Alzheimer’s disease. In October 2017, we presented positive pharmacokinetic
(“PK”) and pharmacodynamic (“PD”) data from the Phase 2a clinical trial, which established a concentration-effect
relationship between ANAVEX®2-73 and trial measurements. These measures obtained from all patients who participated
in the entire 57 weeks include exploratory cognitive and functional scores as well as biomarker signals of brain activity. Additionally,
the clinical trial appeared to show that ANAVEX®2-73 activity was enhanced by its active metabolite (ANAVEX19-144),
which also targets the SIGMAR1 receptor and has a half-life approximately twice as long as the parent molecule.
Two consecutive trial extensions for the Phase
2a trial have allowed participants who completed the 52-week Part B of the trial to continue taking ANAVEX®2-73,
providing an opportunity to gather extended safety data for a cumulative time period of five years. In August 2020, patients completing
these Phase 2a trial extensions were granted continued access to treatment with ANAVEX®2-73 through the Australian
Government Department of Health – Therapeutic Goods Administration’s compassionate use Special Access Scheme.
A larger Phase 2b/3 double-blind, placebo-controlled
trial of ANAVEX®2-73 in Alzheimer’s disease commenced in August 2018. The Phase 2b/3 trial enrolled 509 patients,
which were treated with a convenient once-daily oral formulation of ANAVEX®2-73 for 48 weeks, randomized 1:1:1 to
two different ANAVEX®2-73 doses or placebo. The trial took place at 52 sites across North America, Europe and Australia.
Primary and secondary endpoints to assess safety and both cognitive and functional efficacy, were measured through the Alzheimer’s
Disease Assessment Scale – Cognitive Subscale test (“ADAS-Cog”), Alzheimer’s Disease Cooperative Study
– Activities of Daily Living (“ADCS-ADL”) and Clinical Dementia Rating – Sum of Boxes for cognition and
function (“CDR-SB”). In addition to the primary endpoints, the ANAVEX®2-73 Phase 2b/3 trial design incorporated
pre-specified statistical analyses related to potential genomic precision medicine biomarkers previously identified in the ANAVEX®2-73
Phase 2a clinical trial. The trial completed in mid-2022 and, in December 2022, the Company presented positive topline results
from the Phase 2b/3 clinical trial.
ANAVEX®2-73 met the co-primary
endpoints ADAS-Cog and ADCS-ADL and key secondary endpoint CDR-SB. ANAVEX®2-73 treatment slowed decline of cognition
and function in patients with early Alzheimer’s disease over 48 weeks. Patients treated with ANAVEX®2-73 had
1.84 times higher odds, or likelihood, to improve cognitively compared to placebo, with a ADAS-Cog score threshold change of -0.5
points or better [Odds Ratio = 1.84 (p = 0.015)]. At clinically significant levels of improvement in function (ADCS-ADL score threshold
change of +3.5 points or better), patients treated with ANAVEX®2-73 had 2.67 times higher odds, or likelihood, to
improve function compared to placebo [Odds Ratio = 2.67 (p = 0.0255)]. Additionally, treatment with ANAVEX®2-73
reduced cognitive decline at end of treatment, measured with the ADAS-Cog, as compared to placebo, by 45%, representing a treatment
difference in mean score change of -1.85 points (p=0.033). Compared to placebo, ANAVEX®2-73 reduced clinical decline
of cognition and function by 27% with mean score difference of -0.42 points (p=0.040) as measured by the CDR-SB. ANAVEX®2-73
was generally safe and well tolerated. All statistical analyses were performed by outside consultancy companies.
In October 2019, we initiated a long-term open
label extension study of ANAVEX®2-73, entitled the ATTENTION-AD trial, for patients who have completed the 48-week
Phase 2b/3 placebo-controlled trial referenced above. This trial extension for an additional two years gives patients the opportunity
to continue their treatment.
Rett Syndrome
In February 2016, we presented positive preclinical
data for ANAVEX®2-73 in Rett syndrome, a rare neurodevelopmental disease. The data demonstrated dose related and
significant improvements in an array of behavioral and gait paradigms in a mouse model with an MECP2-null mutation that causes
neurological symptoms that mimic Rett syndrome. The study was funded by the International Rett Syndrome Foundation (“Rettsyndrome.org”).
In January 2017, we were awarded a financial grant from Rettsyndrome.org of a minimum of $0.6 million to cover some of the costs
of a multicenter Phase 2 clinical trial of ANAVEX®2-73 for the treatment of Rett syndrome. This award was received
in quarterly instalments which commenced during fiscal 2018.
In March 2019, we commenced the first Phase
2 clinical trial in a planned Rett syndrome program of ANAVEX®2-73 for the treatment of Rett syndrome. The clinical
trials are being conducted in a range of patient age demographics and geographic regions, utilizing an oral liquid once-daily formulation
of ANAVEX®2-73.
The first Phase 2 trial, (ANAVEX®2-73-RS-001),
which took place in the United States, was completed in December 2020. This trial was a randomized double-blind, placebo-controlled
safety, tolerability, PK and efficacy trial of oral liquid ANAVEX®2-73 formulation in 25 adult female patients with
Rett syndrome over a 7-week treatment period including ANAVEX®2-73-specific genomic precision medicine biomarkers.
The primary endpoint of the trial was safety. The dosing of 5 mg ANAVEX®2-73 was well-tolerated and demonstrated
dose-proportional PK. All secondary efficacy endpoints of the trial showed statistically significant and clinically meaningful
response in the Rett Syndrome Behaviour Questionnaire (“RSBQ”) response, when compared to placebo, in the intent to
treat (“ITT”) cohort (all participants, p = 0.011). 66.7% of ANAVEX®2-73 treated subjects showed a statistically
significant improvement in RSBQ response as compared to 10% of the subjects on placebo in the ITT cohort (all participants, p =
0.011). ANAVEX®2-73 treatment resulted in a sustained improvement in Clinical Global Impression Improvement (CGI-I)
response throughout the 7-week clinical trial, when compared to placebo in the ITT cohort (all participants, p = 0.014). Consistent
with previous ANAVEX®2-73 clinical trials, patients carrying the common form of the SIGMAR1 gene treated with ANAVEX®2-73
experienced stronger improvements in the prespecified efficacy endpoints.
The
second, international trial of ANAVEX®2-73 for the treatment of Rett syndrome, called the AVATAR trial, commenced
in June 2019. This trial took place in Australia and the United Kingdom using a higher dose than the U.S. based Phase 2
trial for Rett syndrome. The trial was a Phase 3 randomized, double-blind, placebo-controlled trial to evaluate the safety and
efficacy of ANAVEX®2-73 in 33 adult patients over a 7-week treatment period including ANAVEX®2-73
specific precision medicine biomarkers. Based upon the input from the successful U.S. Phase 2 Rett syndrome trial (ANAVEX®2-73-RS-001),
we updated the endpoints for the AVATAR trial (ANAVEX®2-73-RS-002) to appropriately assess the clinically meaningful
outcome following International Conference on Harmonization (ICH) guidelines. These updates were approved by the respective regulatory
authorities in the U.K. and in Australia, respectively, where the AVATAR trial was conducted.
The data from the AVATAR trial was released
in February 2022. The clinical trial met all primary and secondary efficacy and safety endpoints, with consistent improvements
in primary efficacy endpoint, RSBQ response (p = 0.037), and secondary efficacy endpoints, ADAMS (p = 0.010) and CGI-I (p = 0.037)
response. Efficacy endpoints demonstrated statistically significant and clinically meaningful reductions in Rett syndrome symptoms.
Convenient once daily oral liquid doses of up to 30 mg of ANAVEX®2-73 were also well tolerated with good medication
compliance. All patients who participated in the trial were eligible to receive ANAVEX®2-73 under a voluntary open
label extension protocol.
In July 2020, we commenced the third trial
of ANAVEX®2-73 for the treatment of Rett syndrome, called the EXCELLENCE trial. This Phase 2/3 trial in pediatric
patients with Rett syndrome includes trial sites in Australia, the United Kingdom and Canada, and will evaluate the safety and
efficacy of ANAVEX®2-73 in approximately 84 pediatric patients, aged 5 to 18, over a 12-week treatment period incorporating
ANAVEX®2-73 specific precision medicine biomarkers. This trial completed enrollment in February 2023, exceeding
the original enrollment target and topline results are expected in the second half of 2023. All patients who participate in the
trial will be eligible to receive ANAVEX®2-73 under a voluntary open label extension protocol, which is currently
ongoing.
Parkinson’s Disease
In September 2016, we presented positive preclinical
data for ANAVEX®2-73 in an animal model of Parkinson’s disease, which demonstrated significant improvements
on behavioral, histopathological, and neuroinflammatory endpoints. The study was funded by the Michael J. Fox Foundation. Additional
data announced in October 2017 indicated that ANAVEX®2-73 induced robust neurorestoration in experimental Parkinsonism.
We believe the encouraging results we have gathered in this preclinical model, coupled with the favorable profile of this product
candidate in the Alzheimer’s disease trial, support the notion that ANAVEX®2-73 has the potential to treat
Parkinson’s disease dementia.
In October 2020, we completed a double-blind,
randomized, placebo-controlled proof-of-concept Phase 2 trial with ANAVEX®2-73 in Parkinson’s disease dementia
in Spain and Australia, to study the effect of the compound on both the cognitive and motor impairment of Parkinson’s disease.
The Phase 2 trial enrolled approximately 132 patients for 14 weeks, randomized 1:1:1 to two different ANAVEX®2-73
doses, 30 mg and 50 mg, or placebo. The ANAVEX®2-73 Phase 2 Parkinson’s disease dementia trial design incorporated
genomic precision medicine biomarkers identified in the ANAVEX®2-73 Phase 2a Alzheimer’s disease trial.
The trial demonstrated that ANAVEX®2-73
was safe and well tolerated in oral doses up to 50 mg once daily. The results showed clinically meaningful, dose-dependent, and
statistically significant improvements in the Cognitive Drug Research (“CDR”) computerized assessment system analysis.
Treatment with ANAVEX®2-73 also resulted in clinically meaningful improvements as measured by the global composite
score of Parkinson’s disease symptom severity, MDS-Unified Parkinson’s Disease Rating Scale total score on top of standard
of care including dopaminergic therapy, levodopa and other anti-PD medications after 14 weeks of treatment, suggesting ANAVEX®2-73’s
potential capability of slowing and reversing symptoms that progress in Parkinson’s disease. In addition, the trial confirmed
the precision medicine approach of targeting SIGMAR1 as a genetic biomarker in response to ANAVEX®2-73 may result
in improved clinical outcomes.
In January 2021, we were awarded a research
grant of $1.0 million from The Michael J. Fox Foundation for Parkinson’s Research to develop ANAVEX®2-73
for the treatment of Parkinson’s disease. The award will explore utilization of PET imaging biomarkers to enable measurement
of target engagement and pathway activation of the SIGMAR1 with clinically relevant doses including in people with Parkinson’s
disease.
Frontotemporal Dementia
In July 2020, we commenced the First-in-Human
Phase 1 clinical trial of ANAVEX®3-71. ANAVEX®3-71 was previously granted orphan drug designation
for the treatment of Frontotemporal Dementia (“FTD”) by the FDA. ANAVEX®3-71 is an orally administered
small molecule targeting sigma-1 and M1 muscarinic receptors that is designed to be beneficial for neurodegenerative diseases.
In preclinical studies, ANAVEX®3-71 demonstrated disease-modifying activity
against the major hallmarks of Alzheimer’s disease in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid and
tau pathologies, as well as beneficial effects on mitochondrial dysfunction and neuroinflammation.
The Phase
1 clinical trial was a prospective double-blind, randomized, placebo-controlled trial in Australia. A total of 36 healthy male
and female subjects were included. Single escalating doses of ANAVEX®3-71 were administered in order to evaluate
the safety, tolerability, and PK of ANAVEX®3-71 and the effects of food and gender on its PK in healthy volunteers.
The trial
met its primary and secondary endpoints of safety, with no serious adverse events (“SAEs”) or dose-limiting toxicities
observed. ANAVEX®3-71 was well tolerated in all cohorts receiving ANAVEX®3-71 in single doses ranging
from 5 mg to 200 mg daily with no SAEs and no significant lab abnormalities in any subject. In the trial, ANAVEX®3-71
exhibited linear PK. Its pharmacokinetics was also dose proportional for doses up to 160 mg. Gender had no effect on the PK of
the drug and food had no effect on the bioavailability of ANAVEX®3-71. The trial also met the secondary objective
of characterizing the effect of ANAVEX®3-71 on electrocardiogram (“ECG”) parameters. There were no clinically
significant ECG parameters throughout the trial. Participant QTcF measures were normal across all dose groups with no difference
between ANAVEX®3-71 and placebo.
Based
on these results, and ANAVEX®3-71’s pre-clinical profile, we intend to advance ANAVEX®3-71
into a biomarker-driven clinical development dementia program for the treatment of schizophrenia, FTD and Alzheimer’s disease,
evaluating longitudinal effect of treatment with ANAVEX®3-71. We believe the results of these clinical trials and
preclinical study could serve as a basis for advancing into respective registration trials in the U.S.
Corporate Information
Our principal executive office is located at
630 5th Avenue, 20th Floor, New York, NY 10111-0100, and our telephone number is (844) 689-3939. Our website address is www.anavex.com.
No information found on our website is part of this prospectus. Also, this prospectus may include the names of various government
agencies or the trade names of other companies. Unless specifically stated otherwise, the use or display by us of such other parties’
names and trade names in this prospectus is not intended to and does not imply a relationship with, or endorsement or sponsorship
of us by, any of these other parties.
THE OFFERING
| Common stock offered by us in the Lincoln Park offering: |
(i) Up to $150,000,000 of shares of our common
stock we may sell to Lincoln Park from time to time until the expiration of the registration statement of which this prospectus
is a part or the earlier termination of the Purchase Agreement;
(ii) 75,000 shares of common stock issued to
Lincoln Park as Initial Commitment Shares in consideration for entering to the Purchase Agreement; and
(iii) Up to 75,000 Additional Commitment Shares,
valued at $844,500 based on a price of $11.26 per share, the closing price of our common stock on The Nasdaq Capital Market on
February 3, 2023, which is the amount of additional shares we may issue for no cash consideration to Lincoln Park from time to
time pro-rata in connection with the purchase of up to $150,000,000 of shares of our common stock under the Purchase Agreement. |
| |
|
| Use of Proceeds |
We intend to use the net proceeds from this offering for general corporate purposes, which may include, among other things, working capital, capital expenditures and funding additional clinical and preclinical development of our pipeline candidates. See “Use of Proceeds” on page S-8. |
| |
|
| Risk Factors |
You should read the “Risk Factors” section on page S-6 of this prospectus supplement and the other risks identified in the documents incorporated by reference herein before making a decision to purchase common stock in this offering. |
| |
|
| Nasdaq Capital Market symbol |
“AVXL.” |
The number of shares of common stock shown
above to be outstanding after this offering is based on 78,032,135 shares of common stock outstanding as of February 3, 2023 and
excludes the following:
| ● | 13,365,296 shares of common stock issuable upon the exercise of outstanding stock options, vested and unvested, with a weighted-
average exercise price of $6.78 per share; and |
| ● | 160,000 shares of common stock issuable upon the exercise of outstanding warrants with a weighted-average exercise price of
$3.72 per share. |
RISK FACTORS
An investment in our common stock involves
a significant degree of risk. Before you invest in our common stock you should carefully consider those risk factors included in
our most recent Annual Report on Form 10-K, our most recent Quarterly Report on Form 10-Q, any subsequently filed Quarterly Reports
on Form 10-Q and any subsequently filed Current Reports on Form 8-K, which are incorporated herein by reference, and those risk
factors that may be included in any applicable prospectus supplement, together with all of the other information included in this
prospectus supplement, the accompanying base prospectus and the documents we incorporate by reference, in evaluating an investment
in our common stock. If any of the risks discussed in the foregoing documents were to occur, our business, financial condition,
results of operations and cash flows could be materially adversely affected. Please read the Section herein entitled “Cautionary
Statement Regarding Forward-Looking Statements.”
Risks Relating to the Purchase Agreement
The sale or issuance of our common
stock to Lincoln Park may cause dilution and the sale of the shares of common stock acquired by Lincoln Park, or the perception
that such sales may occur, could cause the price of our common stock to fall.
On February 3, 2023, we entered into the Purchase
Agreement, pursuant to which Lincoln Park has committed to purchase up to $150,000,000 of shares of our common stock, and, as consideration
for Lincoln Park’s entering into the Purchase Agreement, we have agreed to issue to Lincoln Park an aggregate of up to 150,000
Commitment Shares. Of the 150,000 Commitment Shares, 75,000 shares of common stock were issued to Lincoln Park upon filing this
prospectus supplement and up to an additional 75,000 shares of common stock will be issued pro-rata to Lincoln Park as up to $150,000,000
of shares of our common stock are purchased by Lincoln Park at our discretion from time to time until February 3, 2026 pursuant
to the Purchase Agreement.
The purchase price for the shares that we may
sell to Lincoln Park under the Purchase Agreement will fluctuate based on the price of our common stock. Depending on market liquidity
at the time, sales of such shares may cause the trading price of our common stock to fall.
We have the right to control the timing and
amount of any sales of our shares to Lincoln Park in our sole discretion, subject to certain limits on the amount of shares that
can be sold on a given date. Sales of shares of our common stock, if any, to Lincoln Park will depend upon market conditions and
other factors to be determined by us. Therefore, Lincoln Park may ultimately purchase all, some or none of the shares of our common
stock that may be sold pursuant to the Purchase Agreement and, after it has acquired shares, Lincoln Park may sell all, some or
none of those shares. Sales to Lincoln Park by us could result in substantial dilution to the interests of other holders of our
common stock. Additionally, the sale of a substantial number of shares of our common stock to Lincoln Park, or the anticipation
of such sales, could make it more difficult for us to sell equity or equity-related securities in the future at a time and at a
price that we might otherwise wish to effect sales, which could have a materially adverse effect on our business and operations.
Raising additional capital, including as a result of this
offering, may cause dilution to our existing stockholders, restrict our operations or cause us to relinquish valuable rights.
To raise additional capital, we may in the
future offer additional shares of our common stock at prices that may not be the same as the price per share in this offering.
The price per share at which we sell additional shares of our common stock in future transactions may be higher or lower than the
price per share paid by investors in this offering. In addition, we have a significant number of stock options outstanding. To
the extent that outstanding stock options may be exercised, or other shares issued, you may experience further dilution.
We have broad discretion in the use of
the net proceeds from this offering and may not use them effectively.
Our senior management will have broad discretion
in the application of the net proceeds from this offering. Because of the number and variability of factors that will determine
our use of the net proceeds, their ultimate use may vary substantially from their currently intended use. Our senior management
might not apply our net proceeds in ways that ultimately increase the value of your investment. While we expect to use the net
proceeds from this offering as set forth in the Section herein entitled “Use of Proceeds,” we are not obligated to
do so. The failure by our management to apply these funds effectively could harm our business. If we do not invest or apply the
net proceeds in ways that enhance shareholder value, we may fail to achieve expected financial results, which could adversely affect
our business, financial condition and results of operations, and cause the price of our shares to decline.
The actual number of shares we will issue
to Lincoln Park under the Purchase Agreement, at any one time or in total, is uncertain.
Subject to certain limitations set forth by
the Purchase Agreement with Lincoln Park and compliance with applicable law, we have the discretion to deliver purchase notices
to Lincoln Park at any time throughout the term of the Purchase Agreement. The number of shares that are bought by Lincoln Park
after delivering a purchase notice will fluctuate based on the market price of shares during the sales period and limits we set
with Lincoln Park.
We may not be able to access sufficient
funds under the Purchase Agreement when needed.
Our ability to sell shares to Lincoln Park
and obtain funds under the Purchase Agreement is limited by the terms and conditions in the Purchase Agreement, including restrictions
on the amounts we may sell to Lincoln Park at any one time, and a limitation on our ability to sell shares to Lincoln Park to the
extent that it would cause Lincoln Park to beneficially own more than 4.99% of our outstanding shares of common stock (the “Beneficial
Ownership Limitation”). Additionally, we will only be able to sell or issue to Lincoln Park 15,606,426 shares in total under
the Purchase Agreement, which is equal to 19.99% of the shares of common stock outstanding on the date of the Purchase Agreement
(the “Exchange Cap”) unless we obtain shareholder approval or the average price of such sales exceeds the price of
our common stock on February 3, 2023 as determined under NASDAQ rules. Therefore, we may not in the future have access to the full
amount available to us under the Purchase Agreement, depending on the price of our common stock. In addition, any amounts we sell
under the Purchase Agreement may not satisfy all of our funding needs, even if we are able and choose to sell and issue all of
our common stock currently registered.
Our management might apply the net proceeds from this offering
in ways with which you do not agree and in ways that may impair the value of your investment.
We currently intend to use the net proceeds
from this offering primarily for working capital and general corporate purposes. Our management has broad discretion as to the
use of such proceeds and you will be relying on the judgment of our management regarding the application of these proceeds. Our
management might apply these proceeds in ways with which you do not agree, or in ways that ultimately do not yield a favorable
return. If our management applies such proceeds in a manner that does not yield a significant return, if any, on our investment
of such net proceeds, it could compromise our ability to pursue our growth strategy and adversely affect the market price of our
common stock.
USE OF PROCEEDS
We intend to use the net proceeds from this
offering for general corporate purposes, which may include, among other things, working capital, capital expenditures and funding
additional clinical and preclinical development of our pipeline candidates.
DILUTION
The sale
of our common stock to Lincoln Park pursuant to the Purchase Agreement will have a dilutive impact on our stockholders. In addition,
the lower our stock price is at the time we exercise our right to sell shares to Lincoln Park, the more shares of our common stock
we will have to issue to Lincoln Park pursuant to the Purchase Agreement and our existing stockholders would experience greater
dilution. We calculate
net tangible
book value
per share
by dividing
the net
tangible
book value,
which
is tangible
assets
less
total
liabilities,
by the
number
of outstanding
shares
of common
stock.
Dilution
represents
the difference
between
the portion
of the
amount
per share
paid by purchasers
of shares
in this
offering
and the
as adjusted
net tangible
book value
per share
of our common
stock
immediately
after
giving
effect
to this
offering.
Our net
tangible
book value
as of December
31, 2022 was approximately
$135.1 million, or $1.73 per share.
After
giving
effect
to the
sale of
common
stock
pursuant
to this
prospectus
supplement
and accompanying
prospectus
in the
aggregate
amount
of $150,000,000 at an
assumed
offering
price
of $11.26 per share,
the last
reported
sale price
of our common
stock
on The
Nasdaq
Capital Market
on February 3, 2023, and
after
deducting
estimated
aggregate
offering
expenses
payable
by us, our
net tangible
book value
as of December
31, 2022 would
have
been $285.1 million,
or $3.12 per share
of common
stock.
This
represents
an immediate
increase
in the
net tangible
book value
of $1.39 per share
to our existing
stockholders
and an
immediate
dilution
in net
tangible
book value
of $8.14 per share
to new
investors.
The following
table
illustrates
this
per share
dilution:
| Assumed public offering price per share | |
$ | 11.26 | |
| Net tangible book value per share as of December 31, 2022 | |
$ | 1.73 | |
| Increase per share attributable to new investors | |
$ | 1.39 | |
| As adjusted net tangible book value per share as of December 31, 2022 after giving effect to this offering | |
$ | 3.12 | |
| Dilution per share to new investors purchasing shares in this offering | |
$ | 8.14 | |
The table above assumes for illustrative purposes
that an aggregate of 13,321,492 shares of our common stock are sold pursuant to this prospectus supplement and the accompanying
prospectus at a price of $11.26 per share, the last reported sale price of our common stock on the Nasdaq Capital Market on February
3, 2023, for aggregate gross proceeds of $150,000,000. The shares sold in this offering, if any, will be sold from time
to time at various prices. An increase of $3.00 per share in the price at which the shares are sold from the assumed offering price
of $11.26 per share shown in the table above, assuming all of our common stock in the aggregate amount of $150,000,000 is sold
at that price, would result in an adjusted net tangible book value per share after the offering of $3.21 per share and would increase
the dilution in net tangible book value per share to new investors in this offering to $11.05 per share, after deducting estimated
aggregate offering expenses payable by us. A decrease of $3.00 per share in the price at which the shares are sold from the assumed
offering price of $11.26 per share shown in the table above, assuming all of our common stock in the aggregate amount of $150,000,000
is sold at that price, would result in an adjusted net tangible book value per share after the offering of $2.96 per share and
would decrease the dilution in net tangible book value per share to new investors in this offering to $5.30 per share, after deducting
estimated aggregate offering expenses payable by us.
The above table and discussion are based on
78,032,135 shares of common stock outstanding as of December 31, 2022 and excludes the
following:
| ● | 13,365,296 shares of common stock issuable upon the exercise of outstanding stock options, vested and unvested, with a weighted-average
exercise price of $6.78 per share; and |
| ● | 160,000 shares of common stock issuable upon the exercise of outstanding warrants with a weighted-average exercise price of
$3.72 per share. |
To the extent that options or warrants outstanding
as of December 31, 2022 have been or are exercised, or other shares are issued, investors purchasing shares in this offering could
experience further dilution. In addition, we may choose to raise additional capital due to market conditions or strategic considerations,
even if we believe we have sufficient funds for our current or future operating plans. To the extent that additional capital is
raised through the sale of equity, the issuance of these securities could result in further dilution to our stockholders.
LINCOLN PARK TRANSACTION
On February 3, 2023, we entered into the Purchase
Agreement with Lincoln Park. In connection with the Purchase Agreement, on February 3, 2023, we also entered into a registration
rights agreement (the “Registration Rights Agreement”) with Lincoln Park, pursuant to which we agreed to take specified
actions to maintain the registration of the shares of our common stock subject to the offering described in this prospectus supplement
and accompanying prospectus. Pursuant to the terms of the Purchase Agreement, Lincoln Park has agreed to purchase from us up to
$150,000,000 of shares of our common stock (subject to certain limitations) from time to time at our discretion during the term
of the Purchase Agreement. Pursuant to the terms of the Purchase Agreement and Registration Rights Agreement, we have filed with
the SEC this prospectus supplement regarding the sale under the Securities Act of the shares issuable to Lincoln Park under the
Purchase Agreement.
We may, from time to time and at our sole discretion,
direct Lincoln Park to purchase shares of our common stock upon the satisfaction of certain conditions set forth in the Purchase
Agreement at a purchase price per share based on the market price of our common stock at the time of sale as computed under the
Purchase Agreement. Lincoln Park may not assign or transfer its rights and obligations under the Purchase Agreement.
Under applicable rules of Nasdaq, in no event
may we issue or sell to Lincoln Park under the Purchase Agreement shares of our common stock in excess of 15,606,426 shares (including
the Commitment Shares), which represents 19.99% of the shares of our common stock outstanding immediately prior to the execution
of the Purchase Agreement (the “Exchange Cap”), unless (i) we obtain stockholder approval to issue shares of our common
stock in excess of the Exchange Cap or (ii) the average price of all applicable sales of our common stock to Lincoln Park under
the Purchase Agreement equals or exceeds the official closing price of our common stock on the Nasdaq Capital Market immediately
preceding the date of the Purchase Agreement, plus an incremental amount to account for the issuance of the Additional Commitment
Shares, as calculated in accordance with Nasdaq rules. In any event, the Purchase Agreement specifically provides that we may not
issue or sell any shares of our common stock under the Purchase Agreement if such issuance or sale would breach any applicable
rules or regulations of Nasdaq.
The Purchase Agreement also prohibits us from
directing Lincoln Park to purchase any shares of our common stock if those shares, when aggregated with all other shares of our
common stock then beneficially owned by Lincoln Park, would result in Lincoln Park beneficially owning more than 4.99% of our outstanding
shares of common stock.
Pursuant to the terms of the RRA, which requires
us to register the Purchase Shares and Commitment Shares in order to sell Purchase Shares to Lincoln Park under the Purchase Agreement,
we are filing this prospectus supplement to cover (i) the offer and sale of up to $150,000,000 of shares of our common stock, (ii)
the issuance of 75,000 Initial Commitment Shares, and (iii) the issuance of up to 75,000 Additional Commitment Shares to be issued
pro-rata to Lincoln Park if and when we direct Lincoln Park to purchase available shares of common stock under the Purchase Agreement.
Purchase of Shares Under the Purchase Agreement
Under the Purchase Agreement, we may, from
time to time until February 3, 2026, in our sole discretion and subject to certain conditions outside of Lincoln Park’s control,
direct Lincoln Park to purchase up to 200,000 shares (the “Regular Purchase Share Limit”) of our common stock on any
business day (each such purchase, a “Regular Purchase”); provided that we may mutually agree with Lincoln Park to increase
the Regular Purchase Share Limit to up to 2,000,000 shares and to make multiple purchases in a given day. Additionally, all such
share and dollar amounts shall be appropriately adjusted for any reorganization, recapitalization, non-cash dividend, stock split
or other similar transaction as provided in the Purchase Agreement, and in no event shall Lincoln Park purchase more than $4,000,000
worth of our common stock pursuant to a Regular Purchase on any single business day, provided that the parties may mutually agree
to increase such limit to an amount greater than $4,000,000. The purchase price per share for each such Regular Purchase will be
equal to the lower of:
| |
● |
the lowest sale price for our common stock on the purchase date of such shares; or |
| |
● |
the arithmetic average of the three lowest closing sale prices for our common stock during the ten consecutive business days ending on the business day immediately preceding the purchase date of such shares. |
In addition to Regular Purchases as described
above, we may also direct Lincoln Park, on any business day on which we have properly submitted a Regular Purchase notice directing
Lincoln Park to purchase not less than 50,000 shares of our common stock, to purchase an additional amount of our common stock
(each such purchase, an “Accelerated Purchase”) not to exceed the lesser of:
| |
● |
30% of the aggregate shares of our common stock traded during normal trading hours on the purchase date; and |
| |
● |
1000% of the number of Purchase Shares purchased pursuant to the corresponding Regular Purchase. |
The purchase price per share for each such
Accelerated Purchase will be equal to the lower of 96% of:
| |
● |
the volume weighted average price during (i) the entire trading day on the purchase date, if the volume of shares of our common stock traded on the purchase date has not exceeded a volume maximum calculated in accordance with the Purchase Agreement, or (ii) the portion of the trading day of the purchase date (calculated starting at the beginning of normal trading hours) until such time at which the volume of shares of our common stock traded has exceeded such volume maximum; or |
| |
● |
the closing sale price of our common stock on the purchase date. |
In the event we have properly submitted an
Accelerated Purchase Notice to Lincoln Park to purchase shares of our common stock in the full amount available for an Accelerated
Purchase, on the date of such Accelerated Purchase (which is the business day following the corresponding Regular Purchase), we
may also direct Lincoln Park to purchase an additional amount of our common stock under the same terms set forth above for an Accelerated
Purchase (an “Additional Accelerated Purchase”).
In the case of Regular Purchases, Accelerated
Purchases and Additional Accelerated Purchases, the purchase price per share will be adjusted for any reorganization, recapitalization,
non-cash dividend, stock split, reverse stock split or other similar transaction as set forth in the Purchase Agreement. Other
than as set forth above, there are no trading volume requirements or restrictions under the Purchase Agreement, and we will control
the timing and amount of any sales of our common stock to Lincoln Park.
Upon the filing of this prospectus supplement,
we issued to Lincoln Park 75,000 Commitment Shares and we are obligated to issue up to an additional 75,000 shares of common stock
to Lincoln Park pro-rata in connection with the sale of Purchase Shares to Lincoln Park under the Purchase Agreement, in each case
as consideration for Lincoln Park’s irrevocable commitment to purchase shares of our common stock at our direction under
the Purchase Agreement.
Suspension Events
Suspension events under the Purchase Agreement
include the following:
| ● | the effectiveness of the registration statement of which this prospectus forms a part, or any other
registration statement registering securities under the Purchase Agreement, lapses for any reason (including, without limitation,
the issuance of a stop order), or any required prospectus supplement and accompanying prospectus are unavailable for the sale by
Lincoln Park of our common stock offered hereby, and such lapse or unavailability continues for a period of 10 consecutive business
days or for more than an aggregate of 30 business days in any 365-day period; |
| ● | suspension by our principal market of our common stock from trading on the Nasdaq Capital Market
for a period of three consecutive business days; |
| ● | the delisting of the common stock from the NASDAQ Capital Market; provided, however, that the common
stock is not immediately thereafter trading on the New York Stock Exchange, the NASDAQ Global Market, he NASDAQ Global Select Market,
the NYSE American, the NYSE Arca or the OTC Bulletin Board, OTCQX or OTCQB operated by the OTC Markets Group, Inc. (or nationally
recognized successor to any of the foregoing); |
| ● | our transfer agent’s failure for three business days to issue to Lincoln Park shares of our
common stock which Lincoln Park is entitled to receive under the Purchase Agreement; |
| ● | any breach of the representations or warranties or covenants contained in the Purchase Agreement
or any related agreement which has or which could have a material adverse effect on us subject to a cure period of five business
days; |
| ● | any voluntary or involuntary participation or threatened participation in insolvency or bankruptcy
proceedings by or against us; and |
| ● | if at any time we are not eligible to transfer our common stock electronically as DWAC shares or
a material adverse change in our business, financial condition, operations or prospects has occurred. |
Lincoln Park does not have the right to terminate
the Purchase Agreement upon any of the suspension events set forth above. During a suspension event, all of which are outside of
Lincoln Park’s control, shares of our common stock cannot be sold by us or purchased by Lincoln Park under the Purchase Agreement.
Our Termination Rights
We have the unconditional right, at any time,
for any reason and without any payment or liability to us, to give notice to Lincoln Park to terminate the Purchase Agreement.
In the event of bankruptcy proceedings by or against us, the Purchase Agreement will automatically terminate without action of
any party.
No Short-Selling or Hedging by Lincoln Park
Lincoln Park has agreed that neither it nor
any of its affiliates shall engage in any direct or indirect short-selling or hedging of our common stock during any time prior
to the termination of the Purchase Agreement.
Amount of Potential Proceeds to be Received
under the Purchase Agreement
| Assumed Average Purchase Price Per Share | |
Number of Registered Shares to be Issued if Full Purchase(1)(2) | |
Percentage of Outstanding Shares Issued After Giving Effect to the Issuance to Lincoln Park(3) | |
Proceeds from the Sale of Shares Under the Purchase Agreement Registered in this Offering |
| $ | 8.00 | | |
| 15,469,547 | | |
| 16.7 | % | |
$ | 123,756,376 | |
| | | | |
| | | |
| | | |
| | |
| $ | 10.00 | | |
| 15,000,000 | | |
| 16.2 | % | |
$ | 150,000,000 | |
| | | | |
| | | |
| | | |
| | |
| $ | 11.26 | (4) | |
| 13,321,492 | | |
| 14.7 | % | |
$ | 150,000,000 | |
| | | | |
| | | |
| | | |
| | |
| $ | 13.00 | | |
| 11,538,462 | | |
| 13.0 | % | |
$ | 150,000,000 | |
| | | | |
| | | |
| | | |
| | |
| $ | 15.00 | | |
| 10,000,000 | | |
| 11.5 | % | |
$ | 150,000,000 | |
_______________
| (1) |
Includes the total number of Purchase Shares which we would have sold under the Purchase Agreement at the corresponding assumed purchase price set forth in the adjacent column, up to the additional aggregate purchase price of $150,000,000. Excludes the 75,000 Initial Commitment Shares issued to Lincoln Park upon entering into the Purchase Agreement, and the 75,000 Additional Commitment Shares issuable in connection with sales of Purchase Shares to Lincoln Park. |
| (2) |
The Purchase Agreement prohibits us from issuing or selling (including the Commitment Shares) to Lincoln Park under the Purchase Agreement (A) any shares of our common stock in excess of the Exchange Cap unless (i) we obtain stockholder approval to issue shares of our common stock in excess of the Exchange Cap or (ii) the average price of all applicable sales of our common stock to Lincoln Park under the Purchase Agreement equals or exceeds the official closing price of our common stock on the Nasdaq Capital Market immediately preceding the date of the Purchase Agreement, plus an incremental amount to account for the issuance of the Additional Commitment Shares, as calculated in accordance with Nasdaq rules, and (B) any shares of our common stock if those shares, when aggregated with all other shares of our common stock then beneficially owned by Lincoln Park and its affiliates, would exceed the Beneficial Ownership Limitation. |
| (3) |
The denominator is based on 78,032,135 shares outstanding as of February 3, 2023, adjusted to include the issuance of (i) the 75,000 Commitment Shares issued to Lincoln Park upon the filing of this prospectus supplement, and (ii) the number of shares of common stock (including Additional Commitment Shares) which we would have sold and issued to Lincoln Park, assuming the purchase price in the adjacent column. The numerator is based on the number of Purchase Shares set forth in the adjacent column which we would have sold under the Purchase Agreement at the corresponding assumed purchase price set forth in the adjacent column. |
| (4) |
The closing price of our common stock on February 3, 2023. |
PLAN OF DISTRIBUTION
This prospectus supplement
and the accompanying prospectus include the issuance and sale of up to $150,000,000 of shares of our common stock that we may issue
to Lincoln Park from time to time under the Purchase Agreement and up to an additional 150,000 shares of our common stock that
have been or may be issued by us directly to Lincoln Park under the Purchase Agreement as Commitment Shares for no cash consideration.
This prospectus supplement and the accompanying prospectus also cover the resale of these shares by Lincoln Park to the public.
We entered into the Purchase
Agreement with Lincoln Park on February 3, 2023. The Purchase Agreement provides that, upon the terms and subject to the conditions
set forth therein, Lincoln Park is committed to purchase an aggregate of up to $150 million of shares of our common stock over
the 36-month term of the Purchase Agreement. In consideration for entering into the Purchase Agreement, we are issuing 75,000 shares
of our common stock to Lincoln Park as Initial Commitment Shares, and we are obligated to issue up to an additional 75,000 shares
of our common stock pro-rata as Additional Commitment Shares as shares of our common stock are purchased, all of which are covered
by this prospectus supplement. See the Section herein entitled “Lincoln Park Transaction.”
Lincoln Park is an “underwriter”
within the meaning of Section 2(a)(11) of the Securities Act. Lincoln Park has informed us that it will use an unaffiliated broker-dealer
to effectuate all sales, if any, of the common stock that it may purchase from us pursuant to the Purchase Agreement. Such sales
will be made on the NASDAQ Capital Market at prices and at terms then prevailing or at prices related to the then current market
price. Each such unaffiliated broker-dealer will be an underwriter within the meaning of Section 2(a)(11) of the Securities Act.
Lincoln Park has informed us that each such broker-dealer will receive commissions from Lincoln Park that will not exceed customary
brokerage commissions.
We know of no existing arrangements
between Lincoln Park and any other stockholder, broker, dealer, underwriter, or agent relating to the sale or distribution of the
shares offered by this Prospectus. At the time a particular offer of shares is made, a prospectus supplement, if required, will
be distributed that will set forth the names of any agents, underwriters, or dealers and any compensation from the selling stockholder,
and any other required information.
We will pay all of the expenses
incident to the registration, offering, and sale of the shares to Lincoln Park.
We have agreed to indemnify
Lincoln Park and certain other persons against certain liabilities in connection with the offering of shares of common stock offered
hereby, including liabilities arising under the Securities Act or, if such indemnity is unavailable, to contribute amounts required
to be paid in respect of such liabilities.
Lincoln Park represented
to us that at no time prior to the date of the Purchase Agreement has Lincoln Park or its agents, representatives or affiliates
engaged in or effected, in any manner whatsoever, directly or indirectly, any short sale (as such term is defined in Rule 200 of
Regulation SHO of the Exchange Act) of our common stock or any hedging transaction. Lincoln Park agreed that during the term of
the Purchase Agreement, it, its agents, representatives or affiliates will not enter into or effect, directly or indirectly, any
of the foregoing transactions.
We have advised Lincoln
Park that it is required to comply with Regulation M promulgated under the Exchange Act. With certain exceptions, Regulation M
precludes Lincoln Park, any affiliated purchasers, and any broker-dealer or other person who participates in the distribution from
bidding for or purchasing, or attempting to induce any person to bid for or purchase any security which is the subject of the distribution
until the entire distribution is complete. Regulation M also prohibits any bids or purchases made in order to stabilize the price
of a security in connection with the distribution of that security. All of the foregoing may affect the marketability of the shares
offered by this prospectus supplement.
Nevada Agency and Transfer
Company is transfer agent and registrar for our common stock. Our common stock is listed on The Nasdaq Capital Market under the
symbol “AVXL”.
LEGAL MATTERS
The validity of the securities offered by this
prospectus has been passed upon for us by Snell & Wilmer, L.L.P., Reno, Nevada.
EXPERTS
The audited consolidated financial statements
as of and for the year ended September 30, 2022 and management’s assessment of the effectiveness of internal control over
financial reporting as of September 30, 2022 incorporated by reference in this prospectus and elsewhere in the registration statement
have been so incorporated by reference in reliance upon the reports of Grant Thornton LLP, independent registered public accountants,
upon the authority of said firm as experts in accounting and auditing.
The consolidated financial statements as of
September 30, 2021, and for each of the two years in the period ended September 30, 2021 incorporated in this prospectus by reference
to the Annual Report on Form 10-K for the year ended September 30, 2022 have been incorporated in reliance on the report of BDO
USA, LLP, independent registered public accounting firm, given on the authority of said firm as experts in auditing and accounting.
WHERE YOU CAN FIND MORE INFORMATION
We file annual, quarterly and other reports
and other information with the SEC under the Exchange Act. You may read and copy any reports, statements or other information filed
by us at the SEC’s public reference room at 100 F Street, N.E., Washington, D.C. 20549. Our filings with the SEC are also
available to the public from commercial document retrieval services and at the SEC’s website at www.sec.gov.
We make available free of charge on our internet
website at www.anavex.com our annual reports on Form 10-K, our quarterly reports on Form 10-Q, our current reports on Form 8-K
and any amendments to those reports, as soon as reasonably practicable after we electronically file such material with, or furnish
it to, the SEC. Information contained on our website is not incorporated by reference into this prospectus supplement and you should
not consider such information as part of this prospectus supplement.
DOCUMENTS INCORPORATED BY REFERENCE
The SEC allows us to “incorporate by
reference” into this prospectus certain information that we file with the SEC, which means that we can disclose important
information to you by referring you to other documents separately filed by us with the SEC that contain such information. The information
we incorporate by reference is considered to be part of this prospectus and information we later file with the SEC will automatically
update and supersede the information in this prospectus. The following documents filed by us with the SEC pursuant to Section 13(a)
of the Exchange Act and any of our future filings under Sections 13(a), 13(c), 14 or 15 (d) of the Exchange Act, except for information
furnished under Item 2.02 or 7.01 of Current Report on Form 8-K, or exhibits related thereto, made before the termination of the
offering are incorporated by reference herein:
| 1. | our Annual Report on Form
10-K for the fiscal year
ended September 30, 2022, filed with the SEC on November 28, 2022; |
| 2. | our Quarterly Report on Form 10-Q for the period ended December 31,
2022, filed with the SEC on February 7, 2023; |
| 3. | our Current Report on Form
8-K filed on December 2, 2022; |
| 4. | our Definitive Proxy Statement on Schedule
14A filed on April 11, 2022; and |
| 5. | the description of our common stock contained in the registration statement
on Form 8-A (Registration No. 001-37606), filed with the SEC on October 23, 2015, as updated by Exhibit 4.1 to our Annual Report
on Form 10-K for the fiscal year ended September 30, 2022, filed with the SEC on November 28, 2022, together with any amendment
or report filed for the purpose of updating such description. |
Any statement contained herein or in any document
incorporated or deemed to be incorporated by reference herein shall be deemed to be modified or superseded for the purposes of
this prospectus to the extent that a statement contained herein or in any other subsequently filed document which also is or is
deemed to be incorporated by reference herein modifies or replaces such statement. Any such statement so modified or superseded
shall not be deemed to constitute a part of this prospectus, except as so modified or superseded.
We will provide to each person, including any
beneficial owner, to whom a prospectus is delivered, a copy of any or all of the reports or documents that have been incorporated
by reference in the prospectus contained in the registration statement but not delivered with the prospectus, other than an exhibit
to these filings unless we have specifically incorporated that exhibit by reference into the filing, upon written or oral request
and at no cost to the requester. Requests should be made by writing or telephoning us at the following address:
Anavex Life Sciences Corp.
630 5th Avenue, 20th Floor
New York, NY 10111-0100
(844) 689-3939
PROSPECTUS
Anavex Life Sciences Corp.
$250,000,000 of Common Stock
and Warrants
Anavex Life Sciences Corp., a Nevada corporation (“us”,
“we”, “our”, “Anavex” or the “Company”) may offer and sell
from time to time, in one or more series or issuances and on terms that we will determine at the time of the offering, shares of our common
stock, par value $0.001 per share (“Common Stock”) and warrants (“Warrants”) described in this prospectus,
up to an aggregate amount of $250,000,000.
This prospectus provides you with a general description
of the securities offered. Each time we offer and sell securities, we will file a prospectus supplement to this prospectus that contains
specific information about the offering and, if applicable, the amounts, prices and terms of the securities. Such supplements may also
add, update or change information contained in this prospectus. You should carefully read this prospectus and the applicable prospectus
supplement before you invest in any of our securities. This prospectus may not be used to consummate sales of securities unless accompanied
by a prospectus supplement.
We may offer and sell the securities described in
this prospectus and any prospectus supplement directly to our stockholders or to other purchasers or through agents on our behalf or through
underwriters or dealers as designated from time to time. If any agents or underwriters are involved in the sale of any of these securities,
the applicable prospectus supplement will provide the names of the agents or underwriters and any applicable fees, commission or discounts.
Our Common Stock is currently quoted on the Nasdaq
Capital Market under the symbol “AVXL”. On July 2, 2019, the last reported sale price of our Common Stock was $3.90 per share.
Investing in our securities involves a high degree
of risk. See the section entitled “Risk Factors” on page 11 of this prospectus and in the documents we filed with the Securities
and Exchange Commission that are incorporated in this prospectus by reference for certain risks and uncertainties you should consider.
Neither the Securities and Exchange Commission
nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus.
Any representation to the contrary is a criminal offense.
This prospectus is dated July 15, 2019.
ABOUT THIS PROSPECTUS
This prospectus of Anavex Life Sciences Corp., a Nevada
corporation (collectively with all of its subsidiaries, the “Company”, “Anavex”, or “we”, “us”,
or “our”) is a part of a registration statement on Form S-3 that we filed with the Securities and Exchange Commission (“SEC”)
utilizing a “shelf” registration process. Under this shelf registration process, we may, from time to time, sell the securities
described in this prospectus in one or more offerings up to a total dollar amount of $250,000,000 as described in this prospectus.
The registration statement of which this prospectus
is a part provides additional information about us and the securities offered under this prospectus. The registration statement, including
the exhibits and the documents incorporated herein by reference, can be read on the SEC website or at the SEC offices mentioned under
the heading “Prospectus Summary - Where You Can Find More Information.”
We will provide a prospectus supplement containing
specific information about the amounts, prices and terms of the securities for a particular offering. The prospectus supplement may add,
update or change information in this prospectus. If the information in the prospectus is inconsistent with a prospectus supplement, you
should rely on the information in that prospectus supplement. You should read both this prospectus and, if applicable, any prospectus
supplement. See “Prospectus Summary — Where You Can Find More Information” for more information.
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You should not assume that the information in this prospectus or any prospectus supplement, as well as the information we file or previously
filed with the SEC that we incorporate by reference in this prospectus or any prospectus supplement, is accurate as of any date other
than the date of such document. Our business, financial condition, results of operations and prospects may have changed since those dates.
PROSPECTUS
SUMMARY
The items in the following summary are described
in more detail later in this prospectus. This summary does not contain all of the information you should consider. Before investing in
our securities, you should read the entire prospectus carefully, including the “Risk Factors” beginning on page 11 and the
financial statements incorporated by reference.
Our Current Business
Anavex Life Sciences Corp. is a clinical stage biopharmaceutical
company engaged in the development of differentiated therapeutics by applying precision medicine to central nervous system (“CNS”)
diseases with high unmet need. We analyze genomic data from clinical studies to identify biomarkers, which select patients that will receive
the therapeutic benefit for the treatment of neurodegenerative and neurodevelopmental diseases.
Our lead compound, ANAVEX®2-73, is
being developed to treat Alzheimer’s disease, Parkinson’s disease and potentially other central nervous system diseases, including
rare diseases, such as Rett syndrome, a rare severe neurological monogenic disorder caused by mutations in the X-linked gene, methyl-CpG-binding
protein 2 (“MECP2”).
Our total portfolio currently consists of five programs.
To prioritize the allocation of our resources, we designate certain programs as core programs and others as seed programs, and we currently
have two core programs and three seed programs. Our core programs are at various stages of clinical and preclinical development, in neurodegenerative
and neurodevelopmental diseases.
We have a portfolio of compounds varying in sigma-1
receptor (S1R) binding activities. The SIGMAR1 gene encodes the S1R protein, which is an intracellular chaperone protein with important
roles in cellular communication. S1R is also involved in transcriptional regulation at the nuclear envelope and restores homeostasis and
stimulates recovery of cell function when activated. In order to validate the ability of our compounds to activate quantitatively the
S1R, we performed in collaboration with Stanford University a quantitative Positron Emission Tomography (PET) imaging scan in mice, which
demonstrated a dose-dependent ANAVEX®2-73 target engagement or receptor occupancy (RO) with S1R in the brain.
Cellular Homeostasis
Many diseases are possibly directly caused by chronic
homeostatic imbalances or cellular stress of brain cells. In pediatric diseases like Rett syndrome or infantile spasms, the chronic cellular
stress is possibly caused by the presence of a constant genetic mutation. In neurodegenerative diseases, such as Alzheimer’s and
Parkinson’s diseases, chronic cellular stress is possibly caused by age-correlated buildup of cellular insult and hence chronic
cellular stress. Specifically, defects in homeostasis of protein or ribonucleic acid (“RNA”) lead to the death of neurons
and dysfunction of the nervous system. The spreading of protein aggregates resulting in a proteinopathy, a characteristic finding in Alzheimer’s
and Parkinson’s diseases that results from disorders of protein synthesis, trafficking, folding, processing or degradation in cells.
The clearance of macromolecules in the brain is particularly susceptible to imbalances that result in aggregation and degeneration in
nerve cells. For example, Alzheimer’s disease pathology is characterized by the presence of amyloid plaques, neurofibrillary tangles,
which are aggregates of hyperphosphorylated Tau protein that are a marker of other diseases known as tauopathies as well as inflammation
of microglia. With the SIGMAR1 activation through SIGMAR1 agonists like ANAVEX®2-73, our approach is to restore cellular
balance, i.e. homeostasis. Therapies that correct defects in cellular homeostasis might have the potential to halt or delay neurodevelopmental
and neurodegenerative disease progression.
ANAVEX®2-73-specific Biomarkers
A full genomic analysis of Alzheimer’s disease
(AD) patients treated with ANAVEX®2-73 resulted in the identification of actionable genetic variants. A significant impact
of the genomic biomarkers SIGMAR1, the direct target of ANAVEX®2-73 and COMT, a gene involved in memory function, on the
drug response level was identified, leading to an early ANAVEX®2-73-specific biomarker hypothesis. It is expected that
excluding patients with these two identified biomarker variants (approximately 10%-20% of the population) in prospective studies
would identify approximately 80%-90% patients that would display clinically significant improved functional and cognitive scores. The
consistency between the identified DNA and RNA data related to ANAVEX®2-73, which are considered independent of AD pathology,
as well as multiple endpoints and time-points, provides support for precision medicine clinical development of ANAVEX®2-73
by using genetic biomarkers identified within the study population itself to target patients who are most likely to respond to ANAVEX®2-73
treatment in AD as well as indications like Parkinson’s disease dementia (PDD) or Rett syndrome (RTT) in which ANAVEX®2-73
is currently studied or planned to be studied.
Clinical Studies Overview
In November 2016, we completed a Phase 2a clinical
trial, consisting of PART A and PART B, which lasted a total of 57 weeks, for ANAVEX®2-73 in mild-to-moderate Alzheimer’s
patients. This open-label randomized trial met both primary and secondary endpoints and was designed to assess the safety and exploratory
efficacy of ANAVEX®2-73 in 32 patients. ANAVEX®2-73 targets sigma-1 and muscarinic receptors, which have
been shown in preclinical studies to reduce stress levels in the brain believed to restore cellular homeostasis and to reverse the pathological
hallmarks observed in Alzheimer’s disease. In October 2017, we presented positive pharmacokinetic (PK) and pharmacodynamic (PD)
data from the Phase 2a study, which established a concentration-effect relationship between ANAVEX®2-73 and study measurements.
These measures obtained from all patients who participated in the entire 57 weeks include exploratory cognitive and functional scores
as well as biomarker signals of brain activity. Additionally, the study appears to show that ANAVEX®2-73 activity is enhanced
by its active metabolite (ANAVEX19-144), which also targets the sigma-1 receptor and has a half-life approximately twice as long as the
parent molecule.
In March 2016, we received approval from the Ethics
Committee in Australia to extend the Phase 2a clinical trial by an additional 108 weeks, which had been requested by patients and their
caregivers. Subsequently, in May 2018, we received approval from the Ethics Committee in Australia to further extend the Phase 2a extension
trial for an additional two years. The two consecutive trial extensions have allowed participants who completed the 52-week PART B of
the study to continue taking ANAVEX®2-73, providing an opportunity to gather extended safety data for a cumulative time
period of five years.
In October 2018, we presented new long-term clinical
data for ANAVEX®2-73 in a presentation at the 2018 Clinical Trials on Alzheimer’s Disease (CTAD) Meeting. At 148
weeks into the five-year extended Phase 2a clinical study, data confirmed a significant association between ANAVEX®2-73
concentration and both exploratory functional and cognitive endpoints as measured by the Alzheimer’s Disease Cooperative Study-Activities
of Daily Living (ADCS-ADL) evaluation and the Mini Mental State Examination (MMSE), respectively. The cohort of patients treated
with higher ANAVEX®2-73 concentration maintained ADCS-ADL performance compared to the lower concentration cohort (p<0.0001).
As well, the patient cohort with the higher ANAVEX®2-73 concentration performed better at MMSE compared to the lower concentration
cohort (p<0.0008). A significant impact on the drug response levels of both the SIGMAR1 (p<0.0080) and COMT (p<0.0014) genomic
biomarkers, identified and specified at week 57, was also confirmed over the 148-week period. Further, ANAVEX®2-73 demonstrated
continued favorable safety and tolerability through 148 weeks.
A larger Phase 2b/3 double-blind, placebo-controlled
study of ANAVEX®2-73 in Alzheimer’s disease commenced in October 2018, which is independent of the ongoing Phase
2a extension study. The Phase 2b/3 study will enroll approximately 450 patients for 48 weeks, randomized 1:1:1 to two different ANAVEX®2-73
doses or placebo. The trial is currently taking place in Australia; however, North American sites may also be added. The ANAVEX®2-73
Phase 2b/3 study design incorporates genomic precision medicine biomarkers identified in the ANAVEX®2-73 Phase 2a study.
Primary and secondary endpoints will assess safety and both cognitive and functional efficacy, measured through Alzheimer’s Disease
Assessment Scale – Cognition (ADAS-Cog), ADCS-ADL and Clinical Dementia Rating – Sum of Boxes for cognition and function (CDR-SB).
In February 2016, we presented positive preclinical
data for ANAVEX®2-73 in Rett syndrome, a rare neurodevelopmental disease. The study was funded by the International Rett
Syndrome Foundation (“Rettsyndrome.org”). In January 2017, we were awarded a financial grant from Rettsyndrome.org of a minimum
of $0.6 million to cover some of the costs of a multicenter Phase 2 clinical trial of ANAVEX®2-73 for the treatment of
Rett syndrome. This award is being received in quarterly instalments which commenced during fiscal 2018. Further, in March 2019, the Company
commenced a Phase 2 clinical trial of ANAVEX®2-73 for the treatment of Rett syndrome. The Phase 2 study is taking place
in the United States and is a randomized double-blind, placebo-controlled safety, tolerability, pharmacokinetic and efficacy study of
oral liquid ANAVEX®2-73 formulation to treat Rett syndrome. Pharmacokinetic and dose findings will be investigated in a
total of 15 patients over a 7-week treatment period including ANAVEX®2-73-specific genomic precision medicine biomarkers.
All patients who participate in the study will be eligible to receive ANAVEX®2-73 under a voluntary open label extension
protocol. This study will be followed by a planned placebo-controlled safety and efficacy evaluation of ANAVEX®2-73 over
a 3-month treatment period. Primary and secondary endpoints include safety as well as Rett syndrome conditions such as cognitive impairment,
motor impairment, behavioral symptoms and seizure activity. The ANAVEX®2-73 Phase 2 Rett syndrome study design incorporates
genomic precision medicine biomarkers identified in the ANAVEX®2-73 Phase 2a Alzheimer’s disease study.
In September 2016, we presented positive preclinical
data for ANAVEX®2-73 in Parkinson’s disease, which demonstrated significant improvements on all measures: behavioral,
histopathological, and neuroinflammatory endpoints. The study was funded by the Michael J. Fox Foundation. Additional data was announced
in October 2017 from the model for experimental parkinsonism. The data presented indicates that ANAVEX®2-73 induces robust
neurorestoration in experimental parkinsonism. The encouraging results we have gathered in this model, coupled with the favorable profile
of this compound in the Alzheimer’s disease trial, support the notion that ANAVEX®2-73 is a promising clinical candidate
drug for Parkinson’s disease.
In October 2018, we initiated in Spain, a double-blind,
randomized, placebo-controlled Phase 2 trial with ANAVEX®2-73 in Parkinson’s Disease Dementia (PDD) in Spain, which
will study the effect of the compound on both the cognitive and motor impairment of Parkinson’s disease. The Phase 2 study will
enroll approximately 120 patients for 14 weeks, randomized 1:1:1 to two different ANAVEX®2-73 doses or placebo. The ANAVEX®2-73
Phase 2 PDD study design incorporates genomic precision medicine biomarkers identified in the ANAVEX®2-73 Phase 2a study.
Our Pipeline
Our research and development pipeline includes ANAVEX®2-73
currently in three different clinical studies, and several compounds in different stages of pre-clinical study.
Our proprietary SIGMACEPTOR™ Discovery Platform
produced small molecule drug candidates with unique modes of action, based on our understanding of sigma receptors. Sigma receptors may
be targets for therapeutics to combat many human diseases, both of neurodegenerative nature, including Alzheimer’s disease, as well
as of neurodevelopmental nature, like Rett syndrome. When bound by the appropriate ligands, sigma receptors influence the functioning
of multiple biochemical signals that are involved in the pathogenesis (origin or development) of disease.
Compounds that have been subjects of our research
include the following:
ANAVEX®2-73
ANAVEX®2-73 may offer a disease-modifying
approach in neurodegenerative and neurodevelopmental diseases by activation of sigma-1 receptors.
In Rett syndrome, administration of ANAVEX®2-73
resulted in both significant and dose related improvements in an array of behavioral paradigms in the MECP2 HET Rett syndrome disease
model. In addition, in a further experiment sponsored by Rettsyndrome.org, ANAVEX®2-73 was evaluated in automatic visual
response and respiration tests in 7-month old mice, an age at which advanced pathology is evident. Vehicle-treated MECP2 mice demonstrated
fewer automatic visual responses than wild-type mice. Treatment with ANAVEX®2-73 for four weeks significantly increased
the automatic visual response in the MECP2 Rett syndrome disease mouse. Additionally, chronic oral dosing daily for 6.5 weeks of ANAVEX®2-73
starting at ~5.5 weeks of age was conducted in the MECP2 HET Rett syndrome disease mouse model assessed the different aspects of muscular
coordination, balance, motor learning and muscular strengths, some of the core deficits observed in Rett syndrome. Administration of ANAVEX®2-73
resulted in both significant and dose related improvements in an array of these behavioral paradigms in the MECP2 HET Rett syndrome disease
model.
In March 2019, the Company initiated a Phase 2 clinical
trial of ANAVEX®2-73 for the treatment of Rett syndrome. The Phase 2 study is taking place in the United States and is
a randomized double-blind, placebo-controlled safety, tolerability, pharmacokinetic and efficacy study of oral liquid ANAVEX®2-73
formulation to treat Rett syndrome. Pharmacokinetic and dose finding will be investigated in a total of 15 patients over a 7-week treatment
period using ANAVEX®2-73-specific genomic precision medicine biomarkers. All patients who participate in the study will be eligible
to receive ANAVEX®2-73 under a voluntary open label extension protocol. This study is part of a planned Rett syndrome program.
In May 2016 and June 2016, the FDA granted Orphan
Drug Designation to ANAVEX®2-73 for the treatment of Rett syndrome and infantile spasms, respectively.
For Parkinson’s disease, data demonstrates significant
improvements and restoration of function in a disease modifying animal model of Parkinson’s disease. Significant improvements were
seen on all measures tested: behavioral, histopathological, and neuroinflammatory endpoints. In July 2018 the Company received approval
from the Spanish Agency for Medicinal Products and Medical Devices (AEMPS), to initiate its Phase 2, double-blind, placebo-controlled
14-week trial of the safety and efficacy of ANAVEX®2-73 for the treatment of Parkinson’s disease dementia. The Phase
2 study commenced in October 2018 and will involve approximately 120 patients, randomized 1:1:1 to two different ANAVEX®2-73
doses or placebo, in up to 24 clinical study sites.
In Alzheimer’s disease (AD) animal models, ANAVEX®2-73
has shown pharmacological, histological and behavioral evidence as a potential neuroprotective, anti-amnesic, anti-convulsive and anti-depressive
therapeutic agent, due to its potent affinity to sigma-1 receptors and moderate affinities to M1-4 type muscarinic receptors. In addition,
ANAVEX®2-73 has shown a potential dual mechanism which may impact both amyloid and tau pathology. In a transgenic AD animal
model Tg2576, ANAVEX®2-73 induced a statistically significant neuroprotective effect against the development of oxidative
stress in the mouse brain, as well as significantly increased the expression of functional and synaptic plasticity markers that is apparently
amyloid-beta independent. It also statistically alleviated the learning and memory deficits developed over time in the animals, regardless
of sex, both in terms of spatial working memory and long-term spatial reference memory.
Based on the results of pre-clinical testing, we initiated
and completed a Phase 1 single ascending dose (SAD) clinical trial of ANAVEX®2-73. In this Phase 1 SAD trial, the maximum
tolerated single dose was defined per protocol as 55-60 mg. This dose is above the equivalent dose shown to have positive effects in mouse
models of AD. There were no significant changes in laboratory or electrocardiogram (ECG) parameters. ANAVEX®2-73 was well
tolerated below the 55-60 mg dose with only mild adverse events in some subjects. Observed adverse events at doses above the maximum tolerated
single dose included headache and dizziness, which were moderate in severity and reversible. These side effects are often seen with drugs
that target CNS conditions, including AD.
The ANAVEX®2-73 Phase 1 SAD trial was
conducted as a randomized, placebo-controlled study. Healthy male volunteers between the ages of 18 and 55 received single, ascending
oral doses over the course of the trial. Study endpoints included safety and tolerability together with pharmacokinetic parameters. Pharmacokinetics
includes the absorption and distribution of a drug, the rate at which a drug enters the blood and the duration of its effect, as well
as chemical changes of the substance in the body. This study was conducted in Germany in collaboration with ABX-CRO, a clinical research
organization that has conducted several Alzheimer’s disease studies, and the Technical University of Dresden.
In December 2014, a Phase 2a clinical trial was initiated
for ANAVEX®2-73, which is being evaluated for the treatment of Alzheimer’s disease. The open-label randomized trial
was designed to assess the safety and exploratory efficacy of ANAVEX®2-73 in 32 patients with mild-to-moderate Alzheimer’s
disease. ANAVEX®2-73 targets sigma-1 and muscarinic receptors, which have been shown in preclinical studies to reduce stress
levels in the brain believed to restore cellular homeostasis and to reverse the pathological hallmarks observed in Alzheimer’s disease.
The Phase 2a study met both primary and secondary
objectives of the study. The 31-week preliminary exploratory safety and efficacy data from the Phase 2a study
of ANAVEX®2-73 in Alzheimer’s patients, with most receiving also donepezil, the current standard of care, demonstrated favorable safety,
maximum tolerated dose, positive dose response, sustained efficacy response through 31 weeks for both cognitive and functional measures,
as well as positive unexpected therapeutic response events. ANAVEX®2-73 continued to demonstrate a favorable adverse
event (AE) profile through 31 weeks in a patient population of elderly Alzheimer’s patients with varying degrees of physical
fragility. The most common side effects across all AE categories tended to be of mild severity grade 1 and were resolved with dose
reductions that were anticipated within the adaptive design of the study protocol.
Through 57 weeks, Alzheimer’s
patients taking a daily oral dose between 10mg and 50mg of ANAVEX®2-73 was well tolerated. There were no clinically significant
treatment-related adverse events and no serious adverse events. Despite non-optimized dosing of ANAVEX®2-73 throughout
the 57-week study, continued significant improvements from baseline of cognitive, functional and behavioral scores in a group of patients
were observed, respectively. This data was analyzed using refined mathematical modeling methods in conjunction with the detailed pharmacokinetic
(PK) information.
In October 2017, we presented
positive PK and PD data from the Phase 2a study, which established a concentration-effect relationship between ANAVEX®2-73
and study measurements. These measures, obtained from all patients who participated in the entire 57 weeks, include exploratory cognitive
and functional scores as well as biomarker signals of brain activity. Additionally, the study appears to show that ANAVEX®2-73
activity is enhanced by its active metabolite (ANAVEX19-144), which also targets the sigma-1 receptor and has a half-life approximately
twice as long as the parent molecule.
Pre-specified exploratory
analyses included the cognitive (MMSE) and the functional (ADCS-ADL) changes from baseline. A continued stabilization of both cognitive
and functional measures in patients treated with ANAVEX®2-73 was observed. This correlation was positive within all measured
scores (MMSE, ADCS-ADL, Cogstate, HAM-D and EEG/ERP).
In July 2018, we presented
the results of a genomic DNA and RNA evaluation of the participants in the Phase 2a study. More than 33,000 genes were analyzed using
unbiased, data driven, machine learning, artificial intelligence (AI) system for analyzing DNA & RNA data in patients exposed to ANAVEX®2-73.
The analysis identified genetic variants that impacted response to ANAVEX®2-73, among them variants related to the Sigma-1
receptor (SIGMAR1), the target for ANAVEX®2-73. Results showed that study participants without the SIGMAR1 (rs1800866)
variants, which is about 80 percent of the population worldwide, demonstrated improved cognitive (MMSE) and the functional (ADCS-ADL)
scores. The results from this evaluation may enable a precision medicine approach, since these signatures can now be applied to neurological
indications tested in clinical studies with ANAVEX®2-73 including Alzheimer’s disease, Parkinson’s disease
dementia and Rett syndrome.
ANAVEX®2-73
data presented met prerequisite information in order to progress into a Phase 2b/3 placebo-controlled study. On July 2, 2018, the Human
Research Ethics Committee in Australia approved the initiation of our Phase 2b/3, double-blind, randomized, placebo-controlled 48-week
safety and efficacy trial of ANAVEX®2-73 for the treatment of early Alzheimer’s disease. This Phase 2b/3 study design
incorporates inclusion of genomic precision medicine biomarkers identified in the ANAVEX®2-73 Phase 2a study. The Phase
2b/3 study, which is expected to enroll approximately 450 patients, randomized 1:1:1 to either two different ANAVEX®2-73
doses or placebo, commenced in October 2018.
Preclinical data also validates ANAVEX®2-73
as a prospective platform drug for other neurodegenerative diseases beyond Alzheimer’s disease, Parkinson’s disease or Rett
syndrome, more specifically, epilepsy, infantile spasms, Fragile X syndrome, Angelman syndrome, multiple sclerosis and, more recently,
tuberous sclerosis complex (TSC). ANAVEX®2-73 demonstrated significant improvements in all of these indications in the
respective preclinical animal models.
In a study sponsored by the Foundation for Angelman
Syndrome, ANAVEX®2-73 was assessed in a mouse model for the development of audiogenic seizures. The results indicated that
ANAVEX®2-73 administration significantly reduced audiogenic-induced seizures. In a study sponsored by FRAXA Research Foundation
regarding Fragile X syndrome, data demonstrated that ANAVEX®2-73 restored hippocampal brain-derived neurotrophic factor
(BDNF) expression to normal levels. BDNF under-expression has been observed in many neurodevelopmental and neurodegenerative pathologies.
BDNF signaling promotes maturation of both excitatory and inhibitory synapses. ANAVEX®2-73 normalization of BDNF expression
could be a contributing factor for the positive data observed in both neurodevelopmental and neurodegenerative disorders like Angelman
and Fragile X syndromes.
Preclinical data presented also indicates that ANAVEX®2-73
demonstrates protective effects of mitochondrial enzyme complexes during pathological conditions, which, if impaired, are believed to
play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.
Preclinical data on ANAVEX®2-73 related
to multiple sclerosis indicates that ANAVEX®2-73 may promote remyelination in multiple sclerosis disease. Further, data
also demonstrates that ANAVEX®2-73 provides protection for oligodendrocytes (“OL’s”) and oligodendrocyte
precursor cells (“OPC’s”), as well as central nervous system neurons in addition to helping repair by increasing OPC
proliferation and maturation in tissue culture.
In March 2018, we presented preclinical data of ANAVEX®2-73
in a genetic mouse model of tuberous sclerosis complex (“TSC”). TSC is a rare genetic disorder characterized by the growth
of numerous benign tumors in many parts of the body with a high incidence of seizures. The new preclinical data demonstrates that treatment
with ANAVEX®2-73 significantly increases survival and reduces seizures.
ANAVEX®3-71
ANAVEX®3-71 is a preclinical drug candidate
with a novel mechanism of action via sigma-1 receptor activation and M1 muscarinic allosteric modulation, which has been shown to enhance
neuroprotection and cognition in Alzheimer’s disease models. ANAVEX®3-71 is a CNS-penetrable mono-therapy that bridges
treatment of both cognitive impairments with disease modifications. It is highly effective in very small doses against the major Alzheimer’s
hallmarks in transgenic (3xTg-AD) mice, including cognitive deficits, amyloid and tau pathologies, and also has beneficial effects on
inflammation and mitochondrial dysfunctions. ANAVEX®3-71 indicates extensive therapeutic advantages in Alzheimer’s
and other protein-aggregation-related diseases given its ability to enhance neuroprotection and cognition via sigma-1 receptor activation
and M1 muscarinic allosteric modulation.
A preclinical study examined the response of ANAVEX®3-71
in aged transgenic animal models and showed a significant reduction in the rate of cognitive deficit, amyloid beta pathology and inflammation
with the administration of ANAVEX 3-71. In April 2016, the FDA granted Orphan Drug Designation to ANAVEX®3-71 for the treatment
of Frontotemporal dementia (FTD).
During pathological conditions ANAVEX®3-71
demonstrated the formation of new synapses between neurons (synaptogenesis) without causing an abnormal increase in the number of astrocytes.
In neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, synaptogenesis is believed to be impaired. Additional
preclinical data presented also indicates that in addition to reducing oxidative stress, ANAVEX®3-71 demonstrates protective
effects of mitochondrial enzyme complexes during pathological conditions, which, if impaired, are believed to play a role in the pathogenesis
of neurodegenerative and neurodevelopmental diseases.
ANAVEX®1-41
ANAVEX®1-41 is a sigma-1 agonist. Pre-clinical
tests revealed significant neuroprotective benefits (i.e., protects nerve cells from degeneration or death) through the modulation of
endoplasmic reticulum, mitochondrial and oxidative stress, which damages and impairs cell viability. In addition, in animal models, ANAVEX®1-41
prevented the expression of caspase-3, an enzyme that plays a key role in apoptosis (programmed cell death) and loss of cells in the hippocampus,
the part of the brain that regulates learning, emotion and memory. These activities involve both muscarinic and sigma-1 receptor systems
through a novel mechanism of action.
Preclinical data presented also indicates that ANAVEX®1-41
demonstrates protective effects of mitochondrial enzyme complexes during pathological conditions, which, if impaired, are believed to
play a role in the pathogenesis of neurodegenerative and neurodevelopmental diseases.
ANAVEX®1066
ANAVEX®1066, a mixed sigma-1/sigma-2
ligand is designed for the potential treatment of neuropathic and visceral pain. ANAVEX®1066 was tested in two preclinical
models of neuropathic and visceral pain that have been extensively validated in rats. In the chronic constriction injury model of neuropathic
pain, a single oral administration of ANAVEX®1066 dose-dependently restored the nociceptive threshold in the affected paw
to normal levels while leaving the contralateral healthy paw unchanged. Efficacy was rapid and remained significant for two hours. In
a model of visceral pain, chronic colonic hypersensitivity was induced by injection of an inflammatory agent directly into the colon and
a single oral administration of ANAVEX®1066 returned the nociceptive threshold to control levels in a dose-dependent manner.
Companion studies in rats demonstrated the lack of any effects on normal gastrointestinal transit with ANAVEX®1066 and
a favorable safety profile in a battery of behavioral measures.
Our compounds are in the pre-clinical and clinical
testing stages of development, and there is no guarantee that the activity demonstrated in pre-clinical models will be shown in human
testing.
ANAVEX®1037
ANAVEX®1037 is designed for the treatment
of prostate and pancreatic cancer. It is a low molecular weight, synthetic compound exhibiting high affinity for sigma-1 receptors at
nanomolar levels and moderate affinity for sigma-2 receptors and sodium channels at micromolar levels. In advanced pre-clinical studies,
this compound revealed antitumor potential. It has also been shown to selectively kill human cancer cells without affecting normal/healthy
cells and also to significantly suppress tumor growth in immune-deficient mice models. Scientific publications highlight the possibility
that these ligands may stop tumor growth and induce selective cell death in various tumor cell lines. Sigma receptors are highly expressed
in different tumor cell types. Binding by appropriate sigma-1 and/or sigma-2 ligands can induce selective apoptosis. In addition, through
tumor cell membrane reorganization and interactions with ion channels, our drug candidates may play an important role in inhibiting the
processes of metastasis (spreading of cancer cells from the original site to other parts of the body), angiogenesis (the formation of
new blood vessels) and tumor cell proliferation.
We continue to identify and initiate discussions with
potential strategic and commercial partners to most effectively advance our programs and realize maximum shareholder value. Further, we
may acquire or develop new intellectual property and assign, license, or otherwise transfer our intellectual property to further our goals.
Our Target Indications
We have developed compounds with potential application
to two broad categories and several specific indications. including:
Central Nervous System Diseases
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Alzheimer’s disease – In 2018,
an estimated 5.5 million Americans were suffering from Alzheimer’s disease. The Alzheimer’s Association®
reports that by 2025, 7.1 million Americans will be afflicted by the disease, about a 29 percent increase from currently
affected patients. Medications on the market today treat only the symptoms of Alzheimer’s disease and do not have the ability
to stop its onset or its progression. There is an urgent and unmet need for both a disease modifying cure for Alzheimer’s
disease as well as for better symptomatic treatments. |
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Parkinson’s disease – Parkinson’s disease is a progressive disease of the nervous system marked by tremors, muscular rigidity, and slow, imprecise movement. It is associated with degeneration of the basal ganglia of the brain and a deficiency of the neurotransmitter dopamine. Parkinson’s disease afflicts more than 10 million people worldwide, typically middle-aged and elderly people. The Parkinson’s disease market is set to expand from $2.1 billion in 2014 to $3.2 billion by 2021, according to business intelligence provider GBI Research. |
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Rett syndrome - Rett syndrome is a rare X-linked genetic neurological and developmental disorder that affects the way the brain develops, including protein transcription, which is altered and as a result leads to severe disruptions in neuronal homeostasis. It is considered a rare, progressive neurodevelopmental disorder and is caused by a single mutation in the MECP2 gene. Because males have a different chromosome combination from females, boys who have the genetic MECP2 mutation are affected in devastating ways. Most of them die before birth or in early infancy. For females who survive infancy, Rett syndrome leads to severe impairments, affecting nearly every aspect of the child’s life; severe mental retardation, their ability to speak, walk and eat, sleeping problems, seizures and even the ability to breathe easily. Rett syndrome affects approximately 1 in every 10,000-15,000 females. |
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Depression - Depression is a major cause of morbidity worldwide according to the World Health Organization. Pharmaceutical treatment for depression is dominated by blockbuster brands, with the leading nine brands accounting for approximately 75% of total sales. However, the dominance of the leading brands is waning, largely due to the effects of patent expiration and generic competition. |
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Epilepsy - Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain. According to the Centers for Disease Control and Prevention, epilepsy affects 3.4 million Americans. Today, epilepsy is often controlled, but not cured, with medication that is categorized as older traditional anti-epileptic drugs and second generation anti-epileptic drugs. Because epilepsy afflicts sufferers in different ways, there is a need for drugs used in combination with both traditional anti-epileptic drugs and second generation anti-epileptic drugs. GBI Research estimates that the epilepsy market will increase to $4.5 billion by 2019. |
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Neuropathic Pain – We define neuralgia, or neuropathic pain, as pain that is not related to activation of pain receptor cells in any part of the body. Neuralgia is more difficult to treat than some other types of pain because it does not respond well to normal pain medications. Special medications have become more specific to neuralgia and typically fall under the category of membrane stabilizing drugs or antidepressants. |
Cancer
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Malignant Melanoma - Predominantly a skin cancer, malignant melanoma can also occur in melanocytes found in the bowel and the eye. Malignant melanoma accounts for 75% of all deaths associated with skin cancer. The treatment includes surgical removal of the tumor, adjuvant treatment, chemo and immunotherapy, or radiation therapy. According to IMS Health the worldwide malignant melanoma market is expected to grow to $4.4 billion by 2022. |
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Prostate Cancer – Specific to men, prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. The cancer cells may metastasize from the prostate to other parts of the body, particularly the bones and lymph nodes. Drug therapeutics for prostate cancer are expected to increase to nearly $13.5 billion in 2024 according to Datamonitor Healthcare. |
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Pancreatic Cancer - Pancreatic cancer is a malignant neoplasm of the pancreas. In the United States, approximately 55,000 new cases of pancreatic cancer will be diagnosed this year and approximately 44,000 patients will die as a result of their cancer, according to the American Cancer Society. Sales predictions by GBI Research forecast that the market for the pharmaceutical treatment of pancreatic cancer in the United States and five largest European countries will increase to $2.9 billion by 2021. |
Patents, Trademarks and Intellectual Property
We hold ownership or exclusive rights to five U.S.
patents, eight U.S. patent applications, and various PCT or ex-U.S. patent applications relating to our drug candidates, methods associated
therewith, and to our research programs.
We own one issued U.S. patent entitled “ANAVEX®2-73
and certain anticholinesterase inhibitors composition and method for neuroprotection” claims a composition of matter of ANAVEX®2-73
directed to a novel and synergistic neuroprotective compound combined with donepezil and other cholinesterase inhibitors. This patent
is expected to expire in June 2034, absent any patent term extension for regulatory delays. A related continuation application is also
pending in the U.S. In addition, we own one issued U.S. Patent with claims directed to methods of treating melanoma with a compound related
to ANAVEX®2-73. This patent is expected to expire in February 2030, absent any patent term extension for regulatory delays.
We also own one issued patent with claims directed
to methods for treating or preventing pain with ANAVEX®1066. This patent is expected to expire in November 2036, absent
any patent term extension for regulatory delays.
With regard to ANAVEX®3-71, we own
exclusive rights to two issued U.S. patents with claims respectively directed to the ANAVEX®3-71 compound and methods of
treating various diseases including Alzheimer’s with the same. These patents are expected to expire in April 2030, and January 2030,
respectively, absent any patent term extension for regulatory delays. We also own exclusive rights to related patents or applications
that are granted or pending in Australia, Canada, China, Europe, Japan, Korea, New Zealand, Russia, and South Africa, and are expected
to expire in January 2030.
We also own other patent applications directed to
enantiomers, formulations and uses that may provide additional protection for one or more of our product candidates.
We regard patents and other intellectual property
rights as corporate assets. Accordingly, we attempt to optimize the value of intellectual property in developing our business strategy
including the selective development, protection, and exploitation of our intellectual property rights. In addition to filings made with
intellectual property authorities, we protect our intellectual property and confidential information by means of carefully considered
processes of communication and the sharing of information, and by the use of confidentiality and non-disclosure agreements and provisions
for the same in contractor’s agreements. While no agreement offers absolute protection, such agreements provide some form of recourse
in the event of disclosure, or anticipated disclosure.
Our intellectual property position, like that of many
biomedical companies, is uncertain and involves complex legal and technical questions for which important legal principles are unresolved.
For more information regarding challenges to our existing or future patents, see Item 1A “Risk Factors.”
Recent Developments
On June 6, 2019, we announced that we had dosed the
first patient in our AVATAR Phase 2 double blind, randomized, placebo-controlled safety and efficacy trial of ANAVEX®2-73 for the
treatment of Rett syndrome.
Corporate Information
Our principal executive office is located at 51 West
52nd Street, 7th Floor, New York, NY 10019-6163, and our telephone number is 844.689.3939. Our website address is www.anavex.com.
No information found on our website is part of this prospectus. Also, this prospectus may include the names of various government agencies
or the trade names of other companies. Unless specifically stated otherwise, the use or display by us of such other parties’ names
and trade names in this prospectus is not intended to and does not imply a relationship with, or endorsement or sponsorship of us by,
any of these other parties.
Where You Can Find More Information
We are subject to the information requirements of
the Securities Exchange Act of 1934 (the “Exchange Act”). Accordingly, we file annual, quarterly and current reports,
proxy statements as may be required and other information with the SEC and filed a registration statement on Form S-3 under the Securities
Act relating to the securities offered by this prospectus. This prospectus, which forms part of the registration statement, does not contain
all of the information included in the registration statement. For further information, you should refer to the registration statement
and its exhibits.
You may read and copy the registration statement and
any document we file with the SEC at the SEC’s Public Reference Room at 100 F Street, N.E., Washington, D.C. 20549. Please call
the SEC at 1-800-SEC-0330 for further information on the operation of the Public Reference Room. You can also review our filings by accessing
the website maintained by the SEC at http://www.sec.gov. The site contains reports, proxy and information statements and other
information regarding issuers that file electronically with the SEC. In addition to the foregoing, we maintain a website at http://www.anavex.com.
Our website content is made available for informational purposes only. It should neither be relied upon for investment purposes nor is
it incorporated by reference into this prospectus. We make available at http://www.anavex.com/investors/share-data/ copies of our
Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q and Current Reports on Form 8-K and any amendments to such document as soon
as practicable after we electronically file such material with or furnish such documents to the SEC.
RISK FACTORS
An investment in our securities which may
be offered hereby is subject to numerous risks, including the risks described under the caption “Risk Factors” in
our Annual Report on Form 10-K
for the year ended September 30, 2018, which is incorporated by reference herein. You should carefully consider these risks, along
with the information provided elsewhere in this prospectus and the documents we incorporate by reference in this prospectus before
investing in our securities. You could lose all or part of your investment in the securities. You should consider these matters
in conjunction with the other information included or incorporated by reference in this prospectus. The risks and uncertainties
described in this prospectus, any applicable prospectus supplement and the documents incorporated by reference herein are not
the only ones facing us. Additional risks and uncertainties that we do not presently know about or that we currently believe are
not material may also adversely affect our business. Our business, results of operations or financial condition could be seriously
harmed, and the trading price of our Common Stock may decline due to any of these or other risks.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
This prospectus supplement contains forward-looking
statements. All statements other than statements of historical facts contained in this prospectus supplement, including statements regarding
our anticipated future clinical and regulatory milestone events, future financial position, business strategy and plans and objectives
of management for future operations, are forward-looking statements. The words “believe,” “may,” “estimate,”
“continue,” “anticipate,” “intend,” “expect,” “should,” “forecast,”
“could,” “suggest,” “plan,” and similar expressions, as they relate to us, are intended to identify
forward-looking statements. Such forward-looking statements include, without limitation, statements regarding:
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our ability to successfully conduct clinical and preclinical trials for our product candidates; |
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our ability to raise additional capital on favorable terms; |
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our ability to execute our development plan on time and on budget; |
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our products ability to demonstrate efficacy or an acceptable safety profile; |
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our ability to obtain the support of qualified scientific collaborators; |
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our ability, whether alone or with commercial partners, to successfully commercialize any of our product candidates that may be approved for sale; |
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our ability to identify and obtain additional product candidates; |
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our ability to obtain and maintain sufficient intellectual property protection for our product candidates; |
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our ability to comply with our intellectual property licensing agreements; |
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our ability to defend against claims of intellectual property infringement; |
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our ability to comply with the maintenance requirements of the government patent agencies; |
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our ability to protect our intellectual property rights throughout the world; |
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the anticipated start dates, durations and completion dates of our ongoing and future clinical studies; |
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the anticipated designs of our future clinical studies; |
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our anticipated future regulatory submissions and our ability to receive regulatory approvals to develop and market our product candidates; |
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our anticipated future cash position; and |
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our ability to generate any revenue or to continue as a going concern. |
We have based these forward-looking statements largely
on our current expectations and projections about future events, including the responses we expect from the U.S. Food and Drug Administration,
or FDA, and other regulatory authorities and financial trends that we believe may affect our financial condition, results of operations,
business strategy, preclinical and clinical trials and financial needs. These forward-looking statements are subject to a number of risks,
uncertainties and assumptions including without limitation the risks described in “Risk Factors” in “Part I, Item 1A”
of or Annual Report on Form 10-K for the
fiscal year ended September 30, 2018. These risks are not exhaustive. We operate in a very competitive and rapidly changing environment.
New risk factors emerge from time to time and it is not possible for our management to predict all risk factors, nor can we assess the
impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ
materially from those contained in any forward-looking statements. You should not rely upon forward-looking statements as predictions
of future events. We cannot assure you that the events and circumstances reflected in the forward-looking statements will be achieved
or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable
laws including the securities laws of the United States, we assume no obligation to update or supplement forward-looking statements.
USE OF PROCEEDS
Unless otherwise specified in the applicable prospectus
supplement, we intend to use the net proceeds from the sale of the securities described in this prospectus in connection with the primary
offering for general corporate and operations purposes and to fund our anticipated growth. The applicable prospectus supplement will provide
more details on the use of proceeds of any specific offering.
DILUTION
We will set forth in a prospectus supplement the following
information regarding any material dilution of the equity interests of investors purchasing securities in an offering under this prospectus:
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the net tangible book value per share of
our equity securities before and after the offering; |
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the amount of the increase in such net
tangible book value per share attributable to the cash payments made by purchases in the offering; and |
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the amount of the immediate dilution from
the public offering price which will be absorbed by such purchasers. |
PLAN OF DISTRIBUTION
We may sell the securities described in this prospectus
on a continuous or delayed basis directly to purchasers, through underwriters, broker-dealers or agents that may receive compensation
in the form of discounts, concessions or commissions from us or the purchasers of the securities, in “at the market offerings”
within the meaning of Rule 415(a)(4) of the Securities Act, to or through a market maker or into an existing trading market, on an exchange,
or otherwise or through a combination of any such methods of sale. Discounts, concessions or commissions as to any particular underwriter,
broker-dealer or agent may be in excess of those customary in the types of transactions involved.
The securities may be sold from time to time in one
or more transactions at fixed prices, which may be changed from time to time, at prevailing market prices at the time of sale, at varying
prices determined at the time of sale or at negotiated prices. These sales may be effected in transactions, which may involve crosses
or block transactions:
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on any national securities exchange or quotation service on which the securities may be listed or quoted at the time of sale; |
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in the over-the-counter market; |
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in transactions otherwise than on these exchanges or services or in the over-the-counter market; or |
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through the writing of options, whether the options are listed on an options exchange or otherwise. |
Each time that we use this prospectus to sell our
securities, we shall also provide a prospectus supplement. For each series of securities, the applicable prospectus supplement will set
forth the terms of the offering including:
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the public offering price; |
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the name or names of any underwriters, dealers or agents; |
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the purchase price of the securities; |
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the proceeds from the sale of the securities to us; |
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any underwriting discounts, agency fees, or other compensation payable to underwriters or agents; |
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any discounts or concessions allowed or reallowed or repaid to dealers; and |
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the securities exchanges on which the securities will be listed, if any. |
If we use underwriters in the sale of securities,
the securities will be acquired by the underwriters for their own account. The underwriters may then resell the securities in one or more
transactions at a fixed public offering price or at varying prices determined at the time of sale or thereafter. The securities may be
either offered to the public through underwriting syndicates represented by managing underwriters, or directly by underwriters. The obligations
of the underwriters to purchase the securities will be subject to certain conditions. The underwriters will be obligated to purchase all
the securities offered if they purchase any securities. The public offering price and any discounts or concessions allowed or re-allowed
or paid to dealers may be changed from time to time.
If we use dealers in the sale of securities, we will
sell securities to such dealers as principals. The dealers may then resell the securities to the public at varying prices to be determined
by such dealers at the time of resale. We may solicit offers to purchase the securities directly, and we may sell the securities directly
to institutional or other investors, who may be deemed underwriters within the meaning of the Securities Act with respect to any resales
of those securities. The terms of these sales will be described in the applicable prospectus supplement. If we use agents in the sale
of securities, unless otherwise indicated in the prospectus supplement, they will use their reasonable best efforts to solicit purchases
for the period of their appointment. Unless otherwise indicated in a prospectus supplement, if we sell directly, no underwriters, dealers
or agents would be involved. We will not make an offer of securities in any jurisdiction that does not permit such an offer.
We may grant underwriters who participate in the distribution
of securities an option to purchase additional securities to cover overallotments, if any, in connection with the distribution. Any underwriter
may engage in overallotment, stabilizing transactions, short covering transactions and penalty bids in accordance with SEC orders, rules
and regulations and applicable law. To the extent permitted by applicable law and SEC orders, rules and regulations, an overallotment
involves sales in excess of the offering size, which create a short position. Stabilizing transactions permit bids to purchase the underlying
security so long as the stabilizing bids do not exceed a specified maximum. To the extent permitted by applicable law and SEC orders,
rules and regulations, short covering transactions involve purchases of the securities in the open market after the distribution is completed
to cover short positions. Penalty bids permit the underwriters to reclaim a selling concession from a dealer when the securities originally
sold by the dealer is purchased in a covering transaction to cover short positions. Those activities may cause the price of the Common
Stock to be higher than it would otherwise be. If commenced, the underwriters may discontinue any of the activities at any time.
Any underwriters who are qualified market makers on
the NASDAQ Stock Market may engage in passive market making transactions in our Common Stock on the NASDAQ Stock Market in accordance
with Rule 103 of Regulation M, during the business day prior to the pricing of the offering, before the commencement of offers or sales
of the Common Stock. Passive market makers must comply with applicable volume and price limitations and must be identified as passive
market makers. In general a passive market maker must display its bid at a price not in excess of the highest independent bid for such
security; if all independent bids are lowered below the passive market maker’s bid, however, the passive market maker’s bid
must then be lowered when certain purchase limits are exceeded. The anti-manipulation rules under the Exchange Act may apply to sales
of shares in the market. Furthermore, Regulation M may restrict the ability of any person engaged in the distribution of the shares to
engage in market-making activities for the particular securities being distributed for a period of up to five business days before the
distribution. The restrictions may affect the marketability of the shares and the ability of any person or entity to engage in market-making
activities for the shares.
Underwriters, dealers and agents that participate
in any distribution of securities may be deemed to be underwriters as defined in the Securities Act. Any discounts, commissions or profit
they receive when they resell the securities may be treated as underwriting discounts and commissions under the Securities Act. Only underwriters
named in the prospectus supplement are underwriters of the securities offered in the prospectus supplement. We may have agreements with
underwriters, dealers and agents to indemnify them against certain civil liabilities, including certain liabilities under the Securities
Act, or to contribute with respect to payments that they may be required to make.
We may authorize underwriters, dealers or agents to
solicit offers from certain institutions whereby the institution contractually agrees to purchase the securities from us on a future date
at a specific price. This type of contract may be made only with institutions that we specifically approve. Such institutions could include
banks, insurance companies, pension funds, investment companies and educational and charitable institutions. The underwriters, dealers
or agents will not be responsible for the validity or performance of these contracts.
Each series of securities will be a new issue of securities.
Our Common Stock is quoted on the Nasdaq Capital Market. Unless otherwise specified in the applicable prospectus supplement, our securities
(other than our Common Stock) will not be listed on any exchange. It has not presently been established whether the underwriters, if any,
of the securities will make a market in the securities. If the underwriters make a market in the securities, such market making may be
discontinued at any time without notice.
Agents, dealers and underwriters may be entitled to
indemnification by us against certain civil liabilities, including liabilities under the Securities Act, or to contribution with respect
to payments which the agents, dealers or underwriters may be required to make in respect thereof. Agents, dealers or underwriters may
be customers of, engage in transactions with, or perform services for us and our subsidiaries in the ordinary course of business.
DESCRIPTION OF OUR CAPITAL STOCK
Common Stock
We are authorized to issue 100,000,000 shares of Common
Stock with a par value of $0.001. As of July 2, 2019, we had 51,661,413 shares of Common Stock outstanding. Upon liquidation, dissolution
or winding up of the corporation, the holders of Common Stock are entitled to share ratably in all net assets available for distribution
to stockholders after payment to creditors. The Common Stock is not convertible or redeemable and has no preemptive, subscription or conversion
rights. There are no conversion, redemption, sinking fund or similar provisions regarding the Common Stock. Each outstanding share of
Common Stock is entitled to one vote on all matters submitted to a vote of stockholders. There are no cumulative voting rights.
Each stockholder is entitled to receive the dividends
as may be declared by our board of directors out of funds legally available for dividends and, in the event of liquidation, to share pro
rata in any distribution of our assets after payment of liabilities. Our board of directors is not obligated to declare a dividend. Any
future dividends will be subject to the discretion of our board of directors and will depend upon, among other things, future earnings,
the operating and financial condition of our Company, its capital requirements, general business conditions and other pertinent factors.
It is not anticipated that dividends will be paid in the foreseeable future.
On October 7, 2015, the Company effected a reverse
stock split at a ratio of 1 for 4, whereby every 4 shares of Common Stock became 1 share of Common Stock. The authorized shares of Common
Stock of the Company were therefore proportionally reduced from 400,000,000 to 100,000,000.
Our Common Stock is quoted on the Nasdaq Capital Market
under the trading symbol “AVXL”. On July 2, 2019, the last reported sale price of our Common Stock was $3.90 per share.
Nevada Anti-Takeover Law and Charter and Bylaws Provisions
Nevada Revised Statutes sections 78.378 to 78.3793
provide state regulation over the acquisition of a controlling interest in certain Nevada corporations unless the articles of incorporation
or bylaws of the corporation provide that the provisions of these sections do not apply. The statute creates a number of restrictions
on the ability of a person or entity to acquire control of a Nevada company by setting down certain rules of conduct and voting restrictions
in any acquisition attempt, among other things. The statute is limited to corporations that are organized in the state of Nevada and that
have 200 or more shareholders, at least 100 of whom are shareholders of record and residents of the state of Nevada; and do business in
the state of Nevada directly or through an affiliated corporation. Because of these conditions, the statute does not apply to our Company.
There are no provisions in our articles of incorporation
or our bylaws that would delay, defer or prevent a change in control of our Company.
DESCRIPTION OF WARRANTS
We may issue Warrants from time to time in one or
more series for the purchase of our Common Stock. Warrants may be issued independently or together with any shares of Common Stock or
offered by any prospectus supplement and may be attached to or separate from Common Stock. Each series of Warrants may be issued under
a separate warrant agreement to be entered into between us and a warrant agent, or any other bank or trust company specified in the related
prospectus supplement relating to the particular issue of Warrants. A warrant agent may act as our agent in connection with the Warrants
and would not assume any obligation or relationship of agency or trust for or with any holders of Warrants or beneficial owners of Warrants.
The specific terms of any series of Warrants will be described in the applicable prospectus supplement relating to that series of Warrants
along with any general provisions applicable to that series of Warrants.
The following is a general description of the Warrants
we may issue. The applicable prospectus supplement will describe the specific terms of any issuance of Warrants. The terms of any Warrants
we offer may differ from the terms described in this prospectus. As a result, we will describe in the prospectus supplement the specific
terms of the particular series of Warrants offered by that prospectus supplement. Accordingly, for a description of the terms of a particular
series of Warrants, you should carefully read this prospectus, the applicable prospectus supplement, and the applicable warrant agreement,
which will be filed as an exhibit to the registration statement of which this prospectus forms a part.
Terms
If Warrants are offered by us, the prospectus supplement
will describe the terms of the Warrants, including the following if applicable to the particular offering:
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the title of the Warrants; |
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the total number of Warrants; |
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the number of shares of Common Stock purchasable upon exercise of the Warrants to purchase Common Stock and the price at which such shares of Common Stock may be purchased upon exercise; |
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the date on and after which the Warrants and the related Common Stock will be separately transferable; |
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if applicable, the date on which the right to exercise the Warrants will commence and the date on which this right will expire; |
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if applicable, the minimum or maximum amount of the Warrants which may be exercised at any one time; |
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a discussion of federal income tax, accounting and other special considerations, procedures and limitations relating to the Warrants; and |
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any other terms of the Warrants including terms, procedures and limitations relating to the exchange and exercise of the Warrants. |
Warrants may be exchanged for new warrants of different
denominations, may be presented for registration of transfer, and may be exercised at our principal executive office, the warrant agent
or any other office indicated in the prospectus supplement.
Before the exercise of their Warrants, holders of
Warrants will not have any of the rights of holders of shares of Common Stock, including the right to receive payments of dividends, if
any, on the shares of Common Stock or to exercise any applicable right to vote.
Exercise of Warrants
Each Warrant will entitle the holder to purchase a
number of shares of Common Stock at an exercise price as will in each case be described in, or calculable from, the prospectus supplement
relating to those Warrants. Warrants may be exercised at the times set forth in the prospectus supplement relating to the Warrants. After
the close of business on the expiration date (or any later date to which the expiration date may be extended by us), unexercised Warrants
will become void. Subject to any restrictions and additional requirements that may be set forth in the prospectus supplement relating
thereto, Warrants may be exercised by delivery to the warrant agent, or at our principal executive office or any other office indicated
in the prospectus supplement, of the certificate evidencing the Warrants properly completed and duly executed, and of payment as provided
in the prospectus supplement of the amount required to purchase the shares of Common Stock purchasable upon such exercise. The exercise
price will be the price applicable on the date of payment in full, as set forth in the prospectus supplement relating to the Warrants.
Upon receipt of the payment, and the certificate representing the Warrants to be exercised properly completed and duly executed at our
principal executive office, the warrant agent or any other office indicated in the prospectus supplement, we will, as soon as practicable,
issue and deliver the shares of Common Stock purchasable upon such exercise. If fewer than all of the Warrants represented by that certificate
are exercised, a new certificate will be issued for the remaining amount of Warrants.
The description in the applicable prospectus supplement
and other offering material of any Warrants we offer will not necessarily be complete and will be qualified in its entirety by reference
to the applicable warrant agreement, which will be filed with the SEC if we offer Warrants. For more information on how you can obtain
copies of the applicable warrant agreement if we offer Warrants, see “Where You Can Find More Information”. We urge you to
read the applicable warrant agreement and the applicable prospectus supplement in their entirety.
LEGAL MATTERS
The validity of the securities offered by this prospectus
has been passed upon for us by Snell & Wilmer, L.L.P., Reno, Nevada. If legal matters in connection with offerings made pursuant to
this prospectus are passed upon by counsel for the underwriters, dealers or agents, if any, such counsel will be named in the prospectus
supplement relating to such offering.
EXPERTS
The consolidated financial statements as of September
30, 2018 and 2017 and for each of the three years in the period ended September 30, 2018 and management’s assessment of the effectiveness
of internal control over financial reporting as of September 30, 2018 incorporated by reference in this Prospectus have been so incorporated
in reliance on the reports of BDO USA, LLP, an independent registered public accounting firm, incorporated herein by reference, given
on the authority of said firm as experts in auditing and accounting.
DISCLOSURE OF COMMISSION POSITION ON INDEMNIFICATION
Insofar as indemnification for liabilities arising
under the Securities Act, as amended, may be permitted to directors, officers, and controlling persons of the registrant pursuant to the
Company’s constituent documents, or otherwise, the registrant has been advised that in the opinion of the SEC such indemnification
is against public policy as expressed in the Securities Act and is, therefore, unenforceable. In the event that a claim for indemnification
against such liabilities (other than the payment by the registrant of expenses incurred or paid by a director, officer, or controlling
person in the successful defense of any action, suit, or proceeding) is asserted by such director, officer, or controlling person connected
with the securities being registered, we will, unless in the opinion of our counsel the matter has been settled by controlling precedent,
submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in
the Securities Act and will be governed by the final adjudication of such issue.
DOCUMENTS INCORPORATED BY REFERENCE
The SEC allows us to “incorporate by reference”
into this prospectus certain information that we file with the SEC, which means that we can disclose important information to you by referring
you to other documents separately filed by us with the SEC that contain such information. The information we incorporate by reference
is considered to be part of this prospectus and information we later file with the SEC will automatically update and supersede the information
in this prospectus. The following documents filed by us with the SEC pursuant to Section 13(a) of the Exchange Act and any of our future
filings under Sections 13(a), 13(c), 14 or 15 (d) of the Exchange Act, except for information furnished under Item 2.02 or 7.01 of Current
Report on Form 8-K, or exhibits related thereto, made before the termination of the offering are incorporated by reference herein:
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our Annual Report on Form 10-K for the fiscal year ended September 30, 2018, filed with the SEC on December 12, 2018, and the amendment thereto on Form 10-K/A filed on January 25, 2019; |
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our Proxy Statement on Schedule 14A filed on February 11, 2019 (excluding those portions that are not incorporated by reference into our Annual Report on Form 10-K); |
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our Quarterly Reports on Form 10-Q for the quarters ended December 31, 2018 filed on February 7, 2019 and for the quarter ended March 31, 2019 filed on May 9, 2019; |
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the description of our common stock contained in the Registration Statement on Form 8-A (File No. 001-37606) filed with the SEC on October 23, 2005. |
In addition, all documents subsequently filed by us
pursuant to Section 13(a), 13(c), 14 or 15(d) of the Exchange Act before the date the offering of securities hereunder is terminated or
complete are deemed to be incorporated by reference into, and to be a part of, this prospectus.
We will provide to each person, including any beneficial
owner, to whom a prospectus is delivered, a copy of any or all of the reports or documents that have been incorporated by reference in
the prospectus contained in the registration statement but not delivered with the prospectus, other than an exhibit to these filings unless
we have specifically incorporated that exhibit by reference into the filing, upon written or oral request and at no cost to the requester.
Requests should be made by writing or telephoning us at the following address:
Anavex Life Sciences Corp.
51 West 52nd Street, 7th Floor
New York, NY 10019-6163
(844) 689-3939
Anavex Life Sciences Corp.
Up to $150,000,000 of Common Stock and
Up to 150,000 Shares of Common Stock as Commitment
Shares
PROSPECTUS SUPPLEMENT
February 3, 2023
Anavex Life Sciences (NASDAQ:AVXL)
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