ITEM 1A. RISK FACTORS
Summary of Risk Factors
The following is a summary
of material risks that could affect the Company. This summary may not contain all of our material risks, and it is qualified in its entirety
by the more detailed risk factors set forth below.
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● We are dependent upon our key personnel to achieve our business objectives.
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● The market prices for our common shares are volatile and will fluctuate.
● We are exposed to risks related to currency exchange rates.
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● We currently have limited commercial revenue and may never become profitable.
● There is currently general economic uncertainty in the global markets.
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Risk Factors
Investing in our common
shares involves a high degree of risk. You should carefully consider each of the following risks, together with all other information
set forth in this Annual Form on 10-K, including the consolidated financial statements and the related notes, before making a decision
to buy our common shares. If any of the following risks actually occurs, our business could be harmed. In that case, the trading price
of our common shares could decline, and you may lose all or part of your investment.
Risks Related to our Business
and Industry
Our IntegraSyn manufacturing approach may prove
unsuccessful in achieving yields and/or cost levels required to be economically competitive with alternative methods of manufacturing.
Given the early-stage of development
of the IntegraSyn program and the risks inherent in research and development, it is too early to project the commercial viability of cannabinoids
produced via this process. Potential negative outcomes from this program include but are not limited to:
Our prospects depend on
the success of our Product Candidates which are at early-stages of development with a statistically high probability of failure.
Given the early-stage of
development, we can make no assurance that our research and development programs will result in regulatory approval or commercially viable
products. To achieve profitable operations, we, alone or with others, must successfully develop, gain regulatory approval, and market
our future products. We currently have no products that have been approved by the FDA, HC, or any similar regulatory authority. To obtain
regulatory approvals for our Product Candidates being developed and to achieve commercial success, clinical trials must demonstrate that
the Product Candidates are safe for human use and that they demonstrate efficacy. We have no products or technologies which are currently
in human clinical trials. Additionally, we have no products for commercial sale or licensed for commercial sale, nor do we expect to
have any such products for the next several years.
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Many potential pharmaceuticals products never reach the stage of clinical testing and
even those that do have only a small chance of successfully completing clinical development and gaining regulatory approval. Our Product
Candidates may fail for a number of reasons, including, but not limited to, being unsafe for human use or due to the failure to provide
therapeutic benefits equal to or better than the standard of treatment at the time of testing. Positive results of early preclinical
research may not be indicative of the results that will be obtained in later stages of preclinical or clinical research. Similarly, positive
results from early-stage clinical trials may not be indicative of favorable outcomes in later-stage clinical trials. We can make no assurance
that any future studies, if undertaken, will yield favorable results.
The early-stage of our product
development makes it particularly uncertain whether any of our product development efforts will prove to be successful and meet applicable
regulatory requirements, and whether any of our Product Candidates will receive the requisite regulatory approvals, be capable of being
manufactured at a reasonable cost or be successfully marketed. If we are successful in developing our current and future Product Candidates
into approved products, we will still experience many potential obstacles, such as the need to develop or obtain manufacturing, marketing
and distribution capabilities. If we are unable to successfully commercialize any of our products, our financial condition and results
of operations may be materially and adversely affected.
Even if our Product Candidates
advance through preclinical studies and clinical trials, we may experience difficulties in managing our growth and expanding our operations.
We have limited resources
to carry out objectives for our current and future preclinical studies and clinical trials. Since our inception as a pharmaceutical company
in October 2014, we have conducted numerous preclinical experiments and are currently conducting early-stage clinical trials, which is
a time-consuming, expensive and uncertain process. In addition, while we have experienced management and expect to contract out many of
the activities related to conducting these programs, we are a small company with less than 15 employees and, therefore, have limited internal
resources both to conduct preclinical studies and clinical trials and to monitor third-party providers. As our Product Candidates advance
through preclinical studies and clinical trials, we will need to expand our development, regulatory and manufacturing operations, either
by expanding our internal capabilities or contracting with other organizations to provide these capabilities for us. In the future, we
expect to have to manage additional relationships with collaborators or partners, suppliers and other organizations. Our ability to manage
our operations and future growth will require us to continue to improve our operational, financial and management controls, reporting
systems and procedures.
If we have difficulty
enrolling patients in clinical trials, the completion of the trials may be delayed or cancelled.
As our Product Candidates
advance from preclinical testing to clinical testing, and then through progressively larger and more complex clinical trials, we will
need to enroll an increasing number of patients that meet the eligibility criteria for those trials. The factors that affect our ability
to enroll patients are largely uncontrollable and include, but are not limited to, the following:
● size and nature of the patient population;
● inclusion and exclusion criteria for the trial;
● design of the study protocol;
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● competition with other companies for clinical sites or patients;
● the perceived risks and benefits of the product candidate under study;
● the patient referral practices of physicians; and
● the number, availability, location and accessibility of clinical trial sites.
As a result of the foregoing
factors, we may have difficulty enrolling or maintaining the enrollment of patients in any clinical trials conducted for our products,
which may result in the delay or cancellation of such trials. The delay or cancellation of any clinical trials could shorten any periods
during which we may have the exclusive right to commercialize our Product Candidates or allow our competitors to bring products to market
before us, which would impair our ability to successfully commercialize our Product Candidates and may harm our financial condition, results
of operations and prospects.
If clinical trials of our Product Candidates
fail to demonstrate safety and efficacy to the satisfaction of regulatory authorities or do not otherwise produce positive results, we
would incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization
of our Product Candidates.
Before obtaining marketing
approval from regulatory authorities for the sale of our Product Candidates, we must conduct preclinical studies in animals and extensive
clinical trials in humans to demonstrate the safety and efficacy of the Product Candidates. Clinical testing is expensive and difficult
to design and implement, can take many years to complete and has uncertain outcomes. The outcome of preclinical studies and early clinical
trials may not predict the success of later clinical trials and interim results of a clinical trial do not necessarily predict final results.
A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced clinical trials
due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials. We do not know whether the
clinical trials we may conduct will demonstrate adequate efficacy and safety to result in regulatory approval to market any of our Product
Candidates in any jurisdiction. A product candidate may fail for safety or efficacy reasons at any stage of the testing process. A major
risk we face is the possibility that none of our Product Candidates under development will successfully gain market approval from the
FDA or other regulatory authorities, resulting in us being unable to derive any commercial revenue from them after investing significant
amounts of capital in multiple stages of preclinical and clinical testing.
If we experience delays
in clinical testing, we will be delayed in commercializing our Product Candidates, and our business may be substantially harmed.
We cannot predict whether
any clinical trials will begin as planned, will need to be restructured, or will be completed on schedule, or at all. Our product development
costs will increase if we experience delays in clinical testing. Significant clinical trial delays could shorten any periods during which
we may have the exclusive right to commercialize our Product Candidates or allow our competitors to bring products to market before us,
which would impair our ability to successfully commercialize our Product Candidates and may harm our financial condition, results of operations
and prospects. The commencement and completion of clinical trials for our products may be delayed for a number of reasons, including delays
related, but not limited, to:
● patients failing to enroll or remain in our trials at the rate we expect;
● any changes to our manufacturing process that may be necessary or desired;
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Our product development costs
will increase if we experience delays in testing or approval or if we need to perform more or larger clinical trials than planned. Additionally,
changes in regulatory requirements and policies may occur, and we may need to amend study protocols to reflect these changes. Amendments
may require us to resubmit our study protocols to regulatory authorities or IRBs or ethics committees for re-examination, which may impact
the cost, timing or successful completion of that trial. Delays or increased product development costs may have a material adverse effect
on our business, financial condition and prospects.
Negative results from clinical trials or studies
of others and adverse safety events involving the targets of our products may have an adverse impact on our future commercialization efforts.
From time to time, studies
or clinical trials on various aspects of pharmaceutical products are conducted by academic researchers, competitors or others. The results
of these studies or trials, when published, may have a significant effect on the market for the pharmaceutical product that is the subject
of the study. The publication of negative results of studies or clinical trials or adverse safety events related to our Product Candidates,
or the therapeutic areas in which our Product Candidates compete, could adversely affect the price of our common shares and our ability
to finance future development of our Product Candidates, and our business and financial results could be materially and adversely affected.
We intend to expend our limited resources to
pursue our Product Candidates for certain indications and may fail to capitalize on other Product Candidates or other indications for
our Product Candidates that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial
and managerial resources, we are focusing on research programs relating to our Product Candidates for certain indications, primarily for
the treatment of EB, which concentrates the risk of product failure in the event our Product Candidates prove to be unsafe or ineffective
or inadequate for clinical development or commercialization. As a result, we may forego or delay pursuit of opportunities with other Product
Candidates or for other indications that could later prove to have greater commercial potential. We may also deem it advisable to refocus
our clinical development programs based on clinical trial results.
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The regulatory approval processes of the FDA,
HC, the EMA and other comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable, and if we are
ultimately unable to obtain regulatory approval for our Product Candidates, our business will be substantially harmed.
We are not permitted to market
our Product Candidates in any jurisdiction until we receive formal approval from the appropriate regulatory authorities. For example,
prior to submitting an NDA to the FDA or an MAA to the EMA for approval of our Product Candidates, we will need to complete our preclinical
studies and clinical trials. Successfully completing our clinical program and obtaining approval of an application seeking commercialization
approval is a complex, lengthy, expensive and uncertain process, and the regulatory authorities may delay, limit or deny approval of our
Product Candidates for many reasons, including, among others, because:
In the United States, our
activities are potentially subject to additional regulation by various federal, state and local authorities in addition to the FDA, including,
among others, the Centers for Medicare and Medicaid Services, other divisions of the United States Department of Health and Human Services,
or “HHS”, (for example, the Office of Inspector General), the Department of Justice, or “DOJ”, and individual
United States Attorney offices within the DOJ, and state and local governments. Because of the breadth of these laws and the narrowness
of available statutory and regulatory exemptions, it is possible that some of our business activities could be subject to challenge under
one or more of such laws. If our operations are found to be in violation of any of the federal and state laws described above or any other
governmental regulations that apply to us, we may be subject to penalties, including criminal and significant civil monetary penalties,
damages, fines, imprisonment, exclusion from participation in government programs, injunctions, recall or seizure of products, total or
partial suspension of production, denial or withdrawal of pre marketing product approvals, private “qui tam” actions brought
by individual whistleblowers in the name of the government or refusal to allow us to enter into supply contracts, including government
contracts, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business
and our results of operations. To the extent that any of our products are sold in a foreign country, we may be subject to similar foreign
laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety surveillance, anti-fraud
and abuse laws, and implementation of corporate compliance programs and reporting of payments or transfers of value to healthcare professionals.
Any of these factors, many
of which are beyond our control, could increase development costs, jeopardize our ability to obtain regulatory approval for and successfully
market our Product Candidates and generate product revenue.
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We intend to conduct clinical trials for our
Product Candidates in several international jurisdictions, and acceptance by all regulatory authorities for such “international”
data is not certain.
We intend to conduct clinical
trials for our Product Candidates both inside and outside the United States. To date, all of our clinical development has been conducted
outside of the United States. Ultimately, we plan to submit NDAs for our Product Candidates to the FDA and other regulatory authorities
upon completion of all requisite clinical trials. As an example, although the FDA may accept data from clinical trials conducted outside
the United States, acceptance of such study data by the FDA is subject to certain conditions. For example, the clinical trial must be
conducted in accordance with FDA regulations relating governing human subject protection and the conduct of clinical trials, which are
referred to as “Good Clinical Practice”, or “GCP” requirements and the FDA must be able to validate the data from
the clinical trial through an onsite inspection if it deems such inspection necessary. Where data from foreign clinical trials are intended
to serve as the sole basis for marketing approval in the United States, the FDA will not approve the application on the basis of foreign
data alone unless those data are considered applicable to the U.S. patient population and U.S. medical practice, the clinical trials were
performed by clinical investigators of recognized competence, and the data is considered valid without the need for an on-site inspection
by the FDA or, if the FDA considers such an inspection to be necessary, the FDA is able to validate the data through an on-site inspection
or other appropriate means. In addition, such clinical trials would be subject to the applicable local laws of the foreign jurisdictions
where the clinical trials are conducted. There can be no assurance the FDA or any other regulatory authorities will accept data from clinical
trials conducted outside of the United States or other international jurisdictions. If the FDA or any other regulatory authorities does
not accept any such data, it would likely result in the need for additional clinical trials, which would be costly and time-consuming
and delay aspects of our development plan.
In addition, the conduct of
clinical trials outside the United States could have a significant impact on us. Risks inherent in conducting international clinical trials
include:
● manufacturing, customs, shipment and storage requirements;
● cultural differences in medical practice and clinical research; and
● diminished protection of intellectual property in some countries.
Our Product Candidates contain compounds that
may be classified as “controlled substances”, the use of which may generate public controversy and restrict their development
or commercialization.
If a drug has a potential
for abuse, the NDA or other regulatory submission must include a description and analysis of studies or information related to abuse of
the drug, including a proposal for scheduling (for example, in the U.S. under the federal Controlled Substances Act, or “CSA”).
A description of any studies related to overdosage is also required, including information on dialysis, antidotes, or other treatments,
if known. While we believe there would be relatively minimal abuse potential with our Product Candidates given the low drug concentration
and topical route of administration, we could be incorrect or they may be perceived as having the potential for substance abuse. In either
case, there may be a negative effect on our ability to successfully develop or commercialize our Product Candidates. Since our Product
Candidates contain purified substances that are chemically identical to those occurring in nature, they may, therefore, be classified
as “controlled substances”, and their regulatory approval may generate public controversy. Political and social pressures
and adverse publicity could lead to delays in approval of, and increased expenses for, our Product Candidates. These pressures could also
limit or restrict the introduction and marketing of our Product Candidates. Despite that fact that our APIs, which are the ingredients
that give medicines their effects, are synthetically made and, therefore, we have no interaction with the Cannabis plant, adverse publicity
from Cannabis misuse or adverse side effects from Cannabis or other cannabinoid products may adversely affect the commercial success or
market penetration achievable for our Product Candidates. The nature of our business attracts a high level of public and media interest,
and in the event of any resultant adverse publicity, our reputation may be harmed. Furthermore, if our Product Candidates are classified
as “controlled substances”, they may be subject to import/export and research restrictions that could delay or prevent the
development of our products in various geographical jurisdictions. The successful commercialization of our Product Candidates may require
permits or approvals from regulatory bodies, such as the DEA, that regulate controlled substances.
Research restrictions, product shipment delays
or prohibitions could have a material adverse effect on our business, results of operations and financial condition.
Research on and the
shipment, import and export of our Product Candidates and the API used in our Product Candidates will require research permits, import
and export licenses by many different authorities. For instance, in the United States, the FDA, U.S. Customs and Border Protection, and
the DEA; in Canada, the Canada Border Services Agency, and HC; in Europe, the EMA and the European Commission; in Australia and New Zealand,
the Australian Customs and Border Protection Service, the Therapeutic Goods Administration, the New Zealand Medicines and Medical Device
Safety Authority and the New Zealand Customs Service; and in other countries, similar regulatory authorities, regulate the research on
and import and export of pharmaceutical products that contain controlled substances. Specifically, the import and export process requires
the issuance of import and export licenses by the relevant controlled substance authority in both the importing and exporting country.
We may not be granted, or if granted, maintain, such licenses from the authorities in certain countries. Even if we obtain the relevant
licenses, shipments of API and our Product Candidates may be held up in transit, which could cause significant delays and may lead to
product batches being stored outside required temperature ranges. Inappropriate storage may damage the product shipment resulting in delays
in clinical trials or, upon commercialization, a partial or total loss of revenue from one or more shipments of API or our Product Candidates.
Once shipment is complete, we or the research contractors we are working with may also suffer further delays or restrictions as a result
of regulations governing research on cannabinoids. A delay in a clinical trial or, upon commercialization, a partial or total loss of
revenue from one or more shipments of API or our Product Candidates could have a material adverse effect on our business, results of operations
and financial condition. The aforementioned examples and lists of various authorities that may currently, or in the future, affect our
ability to conduct research on or import or export our Product Candidates and/or API, should not be construed as exhaustive or comprehensive
in any way.
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Healthcare legislation, including potentially
unfavorable pricing regulations or other healthcare reform initiatives, may increase the difficulty and cost for us to obtain marketing
approval of and commercialize our Product Candidates.
Particularly in the United States but also in other jurisdictions,
there have been a number of legislative and regulatory changes and proposed changes in recent years regarding the healthcare system that
could prevent or delay marketing approval of our Product Candidates, restrict or regulate post-approval activities or affect our ability
to profitably sell any Product Candidates for which we obtain marketing approval. Healthcare reform measures that have been and may be
adopted in the future may result in more rigorous coverage criteria, new payment methodologies and in additional downward pressure on
the price that we receive for any approved product, and could seriously harm our future revenue. Any reduction in reimbursement from Medicare
or other government programs may result in a similar reduction in payments from private payors. The implementation of cost containment
measures or other healthcare reforms may compromise our ability to generate revenue, attain profitability or commercialize our products.
Increased scrutiny on drug pricing or changes
in pricing regulations could restrict the amount that we are able to charge for our Product Candidates, which could adversely affect our
revenue and results of operations.
Drug pricing by pharmaceutical
companies is currently under increased scrutiny and is expected to continue to be the subject of intense political and public debate in
the United States and other jurisdictions. Specifically, there have been several recent U.S. Congressional inquiries and hearings with
respect to pharmaceutical drug pricing practices, including in connection with the investigation of specific price increases by several
pharmaceutical companies. Additionally, several states have recently passed laws designed to, among other things, bring more transparency
to drug pricing, and other states may pursue similar initiatives in the future. We cannot predict the extent to which our business may
be affected by these or other potential future legislative or regulatory developments. However, increased scrutiny on drug pricing, negative
publicity related to the pricing of pharmaceutical drugs generally, or changes in pricing regulations could restrict the amount that we
are able to charge for our Product Candidates, which could have a material adverse effect on our revenue and results of operations.
Even if we are able to commercialize our Product
Candidates, they may not receive coverage and adequate reimbursement from third-party payors, which could harm our business.
The availability of reimbursement
by governmental and private payors is essential for most patients to be able to afford their treatments. Sales of our Product Candidates,
if approved, will depend substantially on the extent to which the costs of these Product Candidates will be paid by health maintenance,
managed care, pharmacy benefit and similar healthcare management organizations, or reimbursed by government health administration authorities,
private health coverage insurers and other third-party payors. If reimbursement is not available, or is available only to limited levels,
we may not be able to successfully commercialize our Product Candidates. Even if coverage is provided, the approved reimbursement amount
may not be high enough to allow us to establish or maintain pricing sufficient to realize a sufficient return on our investment.
In the United States, the
Medicare Modernization Act, established the Medicare Part D program and provided authority for limiting the number of drugs that will
be covered in any therapeutic class thereunder. The Medicare Modernization Act, including its cost reduction initiatives, could decrease
the coverage available for any of our approved products. Furthermore, private payors often follow Medicare in setting their own coverage
policies. Therefore, any reduction in coverage that results from the Medicare Modernization Act may result in a similar reduction from
private payors.
There is significant uncertainty
related to the insurance coverage and reimbursement of newly approved products. In the United States, the principal decisions about reimbursement
for new medicines are typically made by the Centers for Medicare & Medicaid Services, or “CMS”, an agency within the HHS,
as CMS decides whether and to what extent a new medicine will be covered and reimbursed under Medicare. Private payors tend to follow
CMS to a substantial degree.
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The intended use of a drug
product by a physician can also affect pricing. For example, CMS could initiate a National Coverage Determination administrative procedure,
by which the agency determines which uses of a therapeutic product would and would not be reimbursable under Medicare. This determination
process can be lengthy, thereby creating a long period during which the future reimbursement for a particular product may be uncertain.
Outside the United States,
particularly in EU Member States, the pricing of prescription drugs is subject to governmental control. In these countries, pricing negotiations
or the successful completion of Health Technology Assessment, or “HTA”, procedures with governmental authorities can take
considerable time after receipt of marketing authorization for a product. In addition, there can be considerable pressure by governments
and other stakeholders on prices and reimbursement levels, including as part of cost containment measures. Certain countries allow companies
to fix their own prices for medicines but monitor and control company profits. Political, economic and regulatory developments may further
complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by
various EU Member States and parallel distribution, or arbitrage between low-priced and high-priced EU member states, can further reduce
net realized prices. In some countries, we or our collaborators may be required to conduct a clinical trial or other studies that compare
the cost-effectiveness of our Product Candidates to other available therapies in order to obtain or maintain reimbursement or pricing
approval. Publication of discounts by third-party payors or authorities may lead to further pressure on the prices or reimbursement levels
within the country of publication and other countries. If reimbursement of any product candidate approved for marketing is unavailable
or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business, financial condition, results of operations
or prospects could be adversely affected.
Our relationships with customers and third-party
payors will be subject to applicable anti-kickback, fraud and abuse, federal exclusion or debarment, and other healthcare laws and regulations,
which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future
earnings.
Healthcare providers, physicians
and third-party payors play a primary role in the recommendation and prescription of any Product Candidates for which we obtain marketing
approval. Our future arrangements with third-party payors and customers may expose us to broadly applicable fraud and abuse and other
healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we market, sell
and distribute our products for which we obtain marketing approval. As a pharmaceutical company, even though we do not and will not control
referrals of healthcare services or bill directly to Medicare, Medicaid or other third-party payors, certain federal and state healthcare
laws and regulations pertaining to fraud and abuse and patients’ rights are and will be applicable to our business. Restrictions
under applicable federal and state healthcare laws and regulations that may affect our ability to operate include the following:
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Comparable laws and regulations
exist in the countries within the European Economic Area, or “EEA”. Although such laws are partially based upon European Union,
or “EU”, law, they may vary from country to country. Healthcare specific, as well as general EU and national laws, regulations
and industry codes constrain, for example, our interactions with government officials and healthcare professionals, and the collection
and processing of personal health data. Non-compliance with any of these laws or regulations could lead to criminal or civil liability.
Efforts to ensure that our
business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It
is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations
or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in violation
of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and
administrative penalties, damages, fines, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid,
and the curtailment or restructuring of our operations. If any physicians or other healthcare providers or entities with whom we expect
to do business are found to not be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions,
including exclusions from government funded healthcare programs.
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Failure to comply with the U.S. Foreign Corrupt
Practices Act, or “FCPA”, the Canadian Corruption of Foreign Public Officials Act, or “CFPOA”, and other global
anti-corruption and anti-bribery laws could subject us to penalties and other adverse consequences.
The FCPA and the CFPOA, as
well as any other applicable domestic or foreign anti-corruption or anti-bribery laws to which we are or may become subject generally
prohibit corporations and individuals from engaging in certain activities to obtain or retain business or to influence a person working
in an official capacity and requires companies to maintain accurate books and records and internal controls, including at foreign-controlled
subsidiaries. It is illegal to pay, offer to pay or authorize the payment of anything of value to any foreign government official, government
staff member, political party or political candidate in an attempt to obtain or retain business or to otherwise influence a person working
in an official capacity.
Compliance with these anti-corruption
laws and anti-bribery laws may be expensive and difficult, particularly in countries in which corruption is a recognized problem. In addition,
these laws present particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government,
and physicians and other hospital employees are considered to be foreign officials. Certain payments by other companies to hospitals in
connection with clinical trials and other work have been deemed to be improper payments to governmental officials and have led to FCPA
enforcement actions.
Our internal control policies
and procedures may not protect us from reckless or negligent acts committed by our employees, future distributors, licensees or agents.
We are currently working to get policies and processes in place to monitor compliance with the FCPA and CFPOA. We can make no assurance
that they will not engage in prohibited conduct, and we may be held liable for their acts under applicable anti-corruption and anti-bribery
laws. Noncompliance with these laws could subject us to investigations, sanctions, settlements, prosecution, other enforcement actions,
disgorgement of profits, significant fines, damages, other civil and criminal penalties or injunctions, suspension or debarment from contracting
with certain persons, the loss of export privileges, whistleblower complaints, reputational harm, adverse media coverage, and other collateral
consequences. Any investigations, actions or sanctions or other previously mentioned harm could have a material negative effect on our
business, operating results and financial condition.
Recent federal legislation and actions by state
and local governments may permit reimportation of drugs from/to foreign countries where the drugs are sold at lower prices than in the
country of origination, which could materially adversely affect our business and financial condition.
We may face competition for
our Product Candidates, if approved, from cheaper generics and/or cannabinoid therapies sourced from foreign countries that have placed
price controls on pharmaceutical products. This is referred to as parallel importation. For instance, the Medicare Modernization Act contains
provisions that may change U.S. importation laws and expand pharmacists’ and wholesalers’ ability to import cheaper versions
of an approved drug and competing products from Canada, where there are government price controls. These changes to U.S. importation laws
will not take effect unless and until the Secretary of HHS certifies that the changes will pose no additional risk to the public’s
health and safety and will result in a significant reduction in the cost of products to consumers. The Secretary of HHS has so far declined
to approve a reimportation plan. Proponents of drug reimportation, including certain state legislatures, may attempt to pass legislation
that would directly allow reimportation under certain circumstances. Legislation or regulations allowing the reimportation of drugs, if
enacted, could decrease the price we receive for any products that we may develop, including our Product Candidates, and adversely affect
our future revenues and prospects for profitability.
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We are dependent upon
our key personnel to achieve our business objectives.
We depend on key personnel,
the loss of any of whom could harm our business. Our future performance and development will depend to a significant extent on the efforts
and abilities of its executive officers, key employees, and consultants. The loss of the services of one or more of these individuals
could harm our business. Our success will depend largely on our continuing ability to attract, develop and retain skilled employees and
consultants in our business. Because of the specialized scientific and managerial nature of our business, we rely heavily on our ability
to attract and retain qualified scientific, technical and managerial personnel. The competition for qualified personnel in our field is
intense. Due to this intense competition, we may be unable to continue to attract and retain qualified personnel necessary for the development
of our business or to recruit suitable replacement personnel. Any delay in replacing such persons, or an inability to replace them with
persons of similar expertise, would have a material adverse effect on our business, financial condition and results of operations.
Our employees may engage in misconduct or other
improper activities, including noncompliance with regulatory standards and requirements, which could subject us to significant liability
and harm our reputation.
We are exposed to the risk
of employee fraud or other misconduct. Misconduct by employees could include intentional failures to comply with regulations of domestic
or foreign regulatory authorities. In addition, misconduct by employees could include intentional failures to comply with certain development
standards, to report financial information or data accurately, or to disclose unauthorized activities to us. Employee misconduct could
also involve the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and
serious harm to our reputation. While prohibited, it is not always possible to identify and deter employee misconduct, and the precautions
we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting
us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions
could have a significant impact on our business and results of operations, including the imposition of significant fines or other sanctions.
Our insurance may be insufficient
to cover losses that may occur as a result of our operations.
We currently maintain directors’
and officers’ liability insurance, clinical trial insurance and property and general liability insurance and intend in the future
to obtain shipping and storage insurance for Product Candidates. This insurance may not remain available to us or be obtainable by us
at commercially reasonable rates, and the amount of our coverage may not be adequate to cover any liability we incur. Future increases
in insurance costs, coupled with the increase in deductibles, will result in higher operating costs and increased risk. If we were to
incur substantial liability and such damages were not covered by insurance or were in excess of policy limits, or if we were to incur
such liability at a time when we were not able to obtain liability insurance, our business, results of operations and financial condition
could be materially adversely affected.
There may be changes in
laws, regulations and guidelines which are detrimental to our business.
Our operations are subject
to a variety of laws, regulations and guidelines relating to pharmacology, cannabinoids and drug delivery, as well as laws and regulations
relating to health and safety, the conduct of operations, and the protection of the environment. While, to the knowledge of our management,
we are currently in compliance with all such laws, changes to such laws, regulations and guidelines due to matters beyond our control
may cause adverse effects to our operations and financial condition. These changes may require us to incur substantial costs associated
with legal and compliance fees and ultimately require us to alter our business plan. In addition, if the governments of Canada or the
United States were to enact or amend laws relating to our industry, it may decrease the size of, or eliminate entirely, the market for
our Product Candidates, may introduce significant new competition into the market and may otherwise potentially materially and adversely
affect our business, results of operations and financial condition.
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If we do not comply with
laws regulating the protection of the environment and health and human safety, our business could be adversely affected.
The research and development
that we carry out either directly or through third-parties involves, and may in the future involve, the use of potentially hazardous materials
and chemicals. Our operations may produce hazardous waste products. Although we believe that our safety procedures for handling and disposing
of these materials comply with the standards mandated by local, state and federal laws and regulations, the risk of accidental contamination
or injury from these materials cannot be eliminated. If an accident occurs, we could be held liable for resulting damages, which could
be substantial. We are also subject to numerous environmental, health and workplace safety laws and regulations and fire and building
codes. Although we maintain workers’ compensation insurance as prescribed by the Province of British Columbia to cover us for costs
and expenses we may incur due to injuries to our employees, this insurance may not provide adequate coverage against potential liabilities.
We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us. Additional federal, state
and local laws and regulations affecting our operations may be adopted in the future. We may incur substantial costs to comply with, and
substantial fines or penalties if we violate, any of these laws or regulations.
Our proprietary information,
or that of our customers, suppliers and business partners, may be lost or we may suffer security breaches.
In the ordinary course of
our business, we may collect and store sensitive data, including intellectual property, data from preclinical studies, clinical trial
data, our proprietary business information and that of our customers, suppliers and business partners, and personally identifiable information
of our customers, clinical trial subjects and employees, in our data centers and on our networks. The secure processing, maintenance and
transmission of this information is critical to our operations. Despite our security measures, our information technology and infrastructure
may be vulnerable to attacks by hackers or breached due to employee error, malfeasance or other disruptions. Although to our knowledge
we have not experienced any such material security breach to date, any such breach could compromise our networks and the information stored
there could be accessed, publicly disclosed, lost or stolen. Any such access, disclosure or other loss of information could result in
legal claims or proceedings, liability under laws that protect the privacy of personal information, regulatory penalties, disrupt our
operations, damage to our ability to obtain patent protection for our Product Candidates, damage to our reputation, and cause a loss of
confidence in our products and our ability to conduct clinical trials, which could adversely affect our business and reputation and lead
to delays in gaining regulatory approvals.
We expect to face intense
competition, often from companies with greater resources and experience than we have.
The pharmaceutical industry
is highly competitive and subject to rapid change. The industry continues to expand and evolve as an increasing number of competitors
and potential competitors enter the market. Many of these competitors and potential competitors have substantially greater financial,
technological, managerial and research and development resources and experience than we have. Some of these competitors and potential
competitors have more experience than we have in the development of pharmaceutical products, including validation procedures and regulatory
matters. Other companies researching in the same disease areas may develop products that are competitive or superior to our Product Candidates.
Other companies working in cannabinoid research may develop products targeting the same diseases that we are focused on that are competitive
or superior to our Product Candidates. In addition, there are non-FDA approved Cannabis / cannabinoid preparations being made available
from companies in the so-called “medical marijuana” industry, which may be competitive to our products. If we are unable to
compete successfully, our commercial opportunities will be reduced and our business, results of operations and financial conditions may
be materially harmed.
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If we receive regulatory approvals, we intend
to market our Product Candidates in multiple jurisdictions where we have limited or no operating experience and may be subject to increased
business and economic risks that could affect our financial results.
If we receive regulatory approvals,
we may plan to market our Product Candidates in jurisdictions where we have limited or no experience in marketing, developing and distributing
our products. Certain markets have substantial legal and regulatory complexities that we may not have experience navigating. We are subject
to a variety of risks inherent in doing business internationally, including risks related to the legal and regulatory environment in non-U.S.
jurisdictions, including with respect to privacy and data security, trade control laws and unexpected changes in laws, regulatory requirements
and enforcement, as well as risks related to fluctuations in currency exchange rates and political, social and economic instability in
foreign countries. If we are unable to manage our international operations successfully, our financial results could be adversely affected.
Controlled substance legislation
may differ in other jurisdictions and could restrict our ability to market our products internationally, which would result in increased
business and economic risks that could affect our financial results.
Controlled substance legislation
may differ in other jurisdictions and could restrict our ability to market our products internationally. Most countries are parties to
the Single Convention on Narcotic Drugs 1961, which governs international trade and domestic control of narcotic substances, including
Cannabis extracts. Countries may interpret and implement their treaty obligations in a way that creates a legal obstacle to our obtaining
marketing approval for Product Candidates in those countries. These countries may not be willing or able to amend or otherwise modify
their laws and regulations to permit our Product Candidates to be marketed or achieving such amendments to the laws and regulations may
take a prolonged period of time. We would be unable to market our Product Candidates in countries with such obstacles in the near future
or perhaps at all without modification to laws and regulations.
Product liability lawsuits
against us could cause us to incur substantial liabilities.
Our use of our Product Candidates
in clinical trials and the sale of our Product Candidates, if approved, exposes us to the risk of product liability claims. Product liability
claims might be brought against us by patients, healthcare providers or others selling or otherwise coming into contact with our Product
Candidates. For example, we may be sued if any product we develop allegedly causes injury or is alleged to be otherwise unsuitable during
product testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing,
defects in design, a failure to warn of dangers inherent in the product, including as a result of interactions with alcohol or other drugs,
negligence, strict liability, and a breach of warranties. Claims could also be asserted under local jurisdiction consumer protection acts.
If we become subject to product liability claims and cannot successfully defend ourselves against them, we could incur substantial liabilities.
In addition, regardless of merit or eventual outcome, product liability claims may result in, among other things:
● withdrawal of patients from our clinical trials;
● substantial monetary awards to patients or other claimants;
● damage to our reputation and exposure to adverse publicity;
● litigation costs;
● distraction of management’s attention from our primary business;
● loss of revenue; and
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Our current clinical trial
liability insurance coverage may not be sufficient to reimburse us for any expenses or losses we may suffer. Moreover, insurance coverage
is becoming increasingly expensive and, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient
amounts to protect us against losses due to liability. If we obtain marketing approval for our Product Candidates, we intend to expand
our insurance coverage to include the sale of commercial products; however, we may be unable to obtain product liability insurance on
commercially reasonable terms or in adequate amounts. Large judgments have been awarded in class action lawsuits based on drugs that had
unanticipated side effects. The cost of any product liability litigation or other proceedings, even if resolved in our favor, could be
substantial, particularly in light of the size of our business and financial resources. A product liability claim or series of claims
brought against us could cause our share price to decline and, if we are unsuccessful in defending such a claim or claims and the resulting
judgments exceed our insurance coverage, our financial condition, results of operations, business and prospects could be materially adversely
affected.
Failure to protect our information technology
infrastructure against cyber-based attacks, network security breaches, service interruptions, or data corruption could significantly disrupt
our operations and adversely affect our business and operating results.
We rely on information technology,
telephone networks and systems, including the internet, to process and transmit sensitive electronic information and to manage or support
a variety of business processes and activities. We use enterprise information technology systems to record, process and summarize financial
information and results of operations for internal reporting purposes and to comply with regulatory, financial reporting, legal and tax
requirements. Despite the implementation of security measures, our information technology systems, and those of our third-party contractors
and consultants, are vulnerable to a cyber-attack, malicious intrusion, breakdown, destruction, loss of data privacy or other significant
disruption. Any such successful attacks could result in the theft of intellectual property or other misappropriation of assets, or otherwise
compromise our confidential or proprietary information and disrupt our operations. Cyber-attacks are becoming more sophisticated and frequent,
and our systems could be the target of malware and other cyber-attacks. We have invested in our systems and the protection of our data
to reduce the risk of an intrusion or interruption, and we monitor our systems on an ongoing basis for any current or potential threats.
Nonetheless, our computer systems are subject to penetration and our data protection measures may not prevent unauthorized access. We
can give no assurances that these measures and efforts will prevent interruptions or breakdowns. If we are unable to detect or prevent
a security breach or cyber-attack or other disruption from occurring, then we could incur losses or damage to our data, or inappropriate
disclosure of our confidential information or that of others; and we could sustain damage to our reputation, suffer disruptions to our
research and development and incur increased operating costs including increased cybersecurity and other insurance premiums, costs to
mitigate any damage caused and protect against future damage, and be exposed to additional regulatory scrutiny or penalties and to civil
litigation and possible financial liability. For instance, the loss of preclinical or clinical data could result in delays in our development
and regulatory filing efforts and significantly increase our costs.
Our failure to comply with data protection
laws and regulations could lead to government enforcement actions and significant penalties against us, and adversely impact our operating
results.
We are subject to various
domestic and international data protection laws and regulations (i.e., laws and regulations that address privacy and data security). The
legislative and regulatory landscape for data protection continues to evolve, and in recent years there has been an increasing focus on
privacy and data security issues. Numerous laws, including data breach notification laws, health information privacy laws and consumer
protection laws, govern the collection, use and disclosure of health-related and other personal information. In addition, we may obtain
health information from third parties (e.g., healthcare providers who prescribe our products) that are subject to privacy and security
requirements under HIPAA regulations.
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EU Member States, Australia
and other countries have also adopted data protection laws and regulations, which impose significant compliance obligations. For example,
the collection and use of personal data in the EU is governed by the provisions of the General Data Protection Regulation, or “GDPR”.
The GDPR and the national implementing legislation of the EU Member States impose strict obligations and restrictions on the ability to
collect, analyze and transfer personal data, including health data from clinical trials and adverse event reporting. In particular, these
obligations and restrictions concern the consent of the individuals to whom the personal data relates, the information provided to the
individuals, the rights of individuals to control personal data and the security and confidentiality of the personal data. In addition,
the Australian Privacy Act 1988 (Cth), and other laws in the states and territories in Australia where we conduct certain of our clinical
trials, apply similar restrictions on our ability to collect, analyze and transfer medical records and other patient data.
A claim or series of claims
brought against us alleging a failure to comply with these laws, or changes in the way in which these laws are implemented, could lead
to government enforcement actions and significant penalties against us, and adversely impact our operating results and could cause our
share price to decline and, if we are unsuccessful in defending such a claim or claims and the resulting judgments exceed our insurance
coverage, our financial condition, results of operations, business and prospects could be materially adversely affected.
The COVID-19 coronavirus
could adversely impact our business, including several key activities that are critical to our success.
The global outbreak of COVID-19
continues to rapidly evolve. As a result, businesses have closed and limits have been placed on travel. The extent to which COVID-19 may
impact our business will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the
ultimate impact of the disease on specific geographies, the duration of the outbreak, travel restrictions and social distancing in the
United States, Canada and other countries, business closures or business disruptions and the effectiveness of actions taken in the United
States, Canada and other countries to contain and treat the disease.
The spread of COVID-19 throughout
the world has also created global economic uncertainty, which may cause partners, suppliers and potential customers to closely monitor
their costs and reduce their spending budget. Any of the foregoing could materially adversely affect our research and development activities,
clinical trials, supply chain, financial condition and cash flows.
If the COVID-19 outbreak continues
to spread, we may need to limit operations or implement other limitations on our activities. There is a risk that countries or regions
outside the United States and Canada may be less effective at vaccinations and containing COVID-19, in which case the risks described
herein could be elevated significantly.
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Risks Related to our Securities
The market prices for
our common shares are volatile and will fluctuate.
The market price for our common
shares may be volatile and subject to wide fluctuations in response to numerous factors, many of which are beyond our control, including
the following: (i) actual or anticipated fluctuations in our quarterly financial results; (ii) recommendations by securities research
analysts; (iii) changes in the economic performance or market valuations of other issuers that investors deem comparable to ours; (iv)
addition or departure of our executive officers or members of our Board and other key personnel; (v) release or expiration of lock-up
or other transfer restrictions on outstanding common shares; (vi) sales or perceived sales of additional common shares; (vii) liquidity
of the common shares; (viii) significant acquisitions or business combinations, strategic partnerships, joint ventures or capital commitments
by or involving us or our competitors; and (ix) news reports relating to trends, concerns, technological or competitive developments,
regulatory changes and other related issues in our industry or target markets. Financial markets often experience significant price and
volume fluctuations that affect the market prices of equity securities of public entities and that are, in many cases, unrelated to the
operating performance, underlying asset values or prospects of such entities. Accordingly, the market price of our common shares may decline
even if our operating results, underlying asset values or prospects have not changed. Additionally, these factors, as well as other related
factors, may cause decreases in asset values that are deemed to be other than temporary, which may result in impairment losses. As well,
certain institutional investors may base their investment decisions on consideration of our environmental, governance and social practices
and performance against such institutions’ respective investment guidelines and criteria, and failure to meet such criteria may
result in limited or no investment in our common shares by those institutions, which could materially adversely affect the trading price
of our common shares. There can be no assurance that continuing fluctuations in price and volume will not occur. If such increased levels
of volatility and market turmoil continue for a protracted period of time, our operations could be materially adversely impacted and the
trading price of our common shares may be materially adversely affected.
Raising additional capital
may cause dilution to our existing shareholders, restrict our operations or require us to relinquish rights to our technologies or Product
Candidates.
We will seek additional capital
through a combination of private and public equity offerings, debt financings, strategic partnerships and alliances and licensing arrangements.
To the extent that we raise additional capital through the sale of equity or convertible debt securities, existing ownership interests
will be diluted and the terms of such financings may include liquidation or other preferences that adversely affect the rights of existing
shareholders. Debt financings may be coupled with an equity component, such as warrants to purchase shares, which could also result in
dilution of our existing shareholders’ ownership. The incurrence of indebtedness would result in increased fixed payment obligations
and could also result in certain restrictive covenants, such as limitations on our ability to incur additional debt, limitations on our
ability to acquire or license intellectual property rights and other operating restrictions that could adversely impact our ability to
conduct our business and may result in liens being placed on our assets and intellectual property. If we were to default on such indebtedness,
we could lose such assets and intellectual property. If we raise additional funds through strategic partnerships and alliances and licensing
arrangements with third parties, we may have to relinquish valuable rights to our Product Candidates or grant licenses on terms that are
not favorable to us.