What changed in this filing

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Item 1A. Risk Factors

2022-03-29 compared with 2021-03-02 · 352 added, 322 removed, 48 unchanged (93% of the section changed)

business and its future performance may be affected by various factors, the most significant of which are discussed below.

are a clinical-stage drug company, have no prescription drug products approved for commercial sale, have incurred substantial

losses, and expect to incur substantial losses and negative operating cash flow for the foreseeable future.

Risks Related to Our Business

are a clinical-stage drug company, have no prescription drug products approved for commercial sale, have incurred substantial losses,

and expect to incur substantial losses and negative operating cash flow for the foreseeable future.

are a clinical-stage drug company that has no prescription drug products approved for commercial sale.

We have never generated

any substantial revenues and may never achieve substantial revenues or profitability.

As of December 31, 2020, we have incurred

net losses of approximately $240 million in the aggregate since inception in January 2002.

We expect to incur substantial losses

and negative operating cash flow for the foreseeable future.

We may never achieve or maintain profitability, even if we succeed

in developing and commercializing one or more of our prescription drug candidates.

We also expect to continue to incur significant

operating expenditures and anticipate that our operating and capital expenses may increase substantially in the foreseeable future

as we continue to develop and seek regulatory approval for our prescription drug candidates PV-10 and PH-10, implement additional

internal systems and infrastructure, and hire additional personnel.

also expect to experience negative operating cash flow for the foreseeable future as we fund our operating losses and any future

capital expenditures.

We have never generated any substantial

revenues and may never achieve substantial revenues or profitability.

As of December 31, 2021, we have incurred net losses of approximately

$246 million in the aggregate since inception in January 2002.

We may never achieve or maintain profitability, even if we succeed in developing and commercializing one

or more of our prescription drug candidates.

We also expect to continue to incur significant operating expenditures and anticipate that

our operating and capital expenses may increase substantially in the foreseeable future as we continue to develop and seek regulatory

approval for our prescription drug candidates PV-10 and PH-10, implement additional internal systems and infrastructure, and hire additional

also expect to experience negative operating cash flow for the foreseeable future as we fund our operating losses and any future capital

expenditures.

As a result, we will need to generate significant revenues in order to achieve and maintain profitability.

We may not be able to generate these revenues or achieve profitability in the future.

Our failure to achieve or maintain profitability

could negatively impact the value of our common stock.

need additional capital to conduct our operations and commercialize and/or further develop our prescription drug candidates in

2021 and beyond, and our ability to obtain the necessary funding is uncertain.

We may not be

able to generate these revenues or achieve profitability in the future.

Our failure to achieve or maintain profitability could negatively

impact the value of our common stock.

need additional capital to conduct our operations and commercialize and/or further develop our prescription drug candidates in 2022 and

beyond, and our ability to obtain the necessary funding is uncertain.

need additional capital in 2022 and beyond to continue developing and seeking to commercialize our drug product candidates.

intend to continue with the development of PV-10 and PH-10 on the basis of historical, ongoing, and prospective clinical study

and/mechanism, of action results.

have based our estimate of capital needs on assumptions that may prove to be wrong, and we cannot assure you that estimates and

assumptions will remain unchanged.

On December 31, 2019, our Board approved a Definitive Financing Term Sheet (the “2020

Term Sheet”), which set forth the terms under which we will use our best efforts to arrange for financing of a maximum of

$20,000,000 (the “2020 Financing”).

We intend to acquire additional funding through the 2020 Financing.

seek capital from public or private equity or debt financings or other financing sources that may be available.

As of December

31, 2020, we have raised $3,325,000 through the 2020 Financing.

intend to continue with the development of PV-10 and PH-10 on the basis of historical, ongoing, and prospective clinical study and

mechanism, of action results.

have based our estimate of capital needs on assumptions that may prove to be wrong, and we cannot assure you that estimates and assumptions

will remain unchanged.

On August 13, 2021, the Board approved a Financing Term Sheet (the “2021 Term Sheet”), which sets

forth the terms under which the Company will use its best efforts to arrange for financing of a maximum of $5,000,000 (the “2021

Financing”), which amounts will be obtained in several tranches and evidenced by convertible promissory notes (collectively,

the “2021 Notes”).

As of December 31, 2021, the Company had received 2021 Notes proceeds of $1,460,000, of which $200,000

is from a related party investor.

additional financing may not be available on acceptable terms, or at all.

As discussed in more detail below, additional equity

financing could result in significant dilution to stockholders.

Further, in the event that additional funds are obtained through

licensing or other arrangements, these arrangements may require us to relinquish rights to some of our products, product candidates,

and technologies that we would otherwise seek to develop and commercialize ourselves.

If sufficient capital is not available,

we may be required to delay, reduce the scope of, or eliminate one or more of our programs, any of which could have a material

adverse effect on our business and may impair the value of our patents and other intangible assets.

As discussed in more detail below, additional equity financing

could result in significant dilution to stockholders.

Further, in the event that additional funds are obtained through licensing or other

arrangements, these arrangements may require us to relinquish rights to some of our products, product candidates, and technologies that

we would otherwise seek to develop and commercialize ourselves.

If sufficient capital is not available, we may be required to delay,

reduce the scope of, or eliminate one or more of our programs, any of which could have a material adverse effect on our business.

is substantial doubt as to our ability to continue as a going concern.

cash and cash equivalents were $97,231 at December 31, 2020, compared with $590,706 at December 31, 2019.

We continue to incur

significant operating losses and management expects that significant on-going operating expenditures will be necessary to successfully

implement our business plan and develop and market our products.

These circumstances raise substantial doubt about our ability

to continue as a going concern for a period of one year from the date that the consolidated financial statements included elsewhere

in this Annual Report on Form 10-K are issued.

Implementation of our plans and our ability to continue as a going concern will

depend upon our ability to develop PV-10 and PH-10, and to raise additional capital.

believes that we have access to capital resources through possible public or private equity offerings, including the 2020 Financing,

exchange offers, debt financings, corporate collaborations or other means.

If we are unable to raise sufficient capital, we will

not be able to pay our obligations as they become due.

cash, cash equivalents, and restricted cash were $3,106,942 at December 31, 2021, which includes $2,423,958 of restricted

cash resulting from a grant received from the State of Tennessee, compared with $97,231 at December 31, 2020.

We continue to incur significant

operating losses and management expects that significant on-going operating expenditures will be necessary to successfully implement

our business plan and develop and market our products.

These circumstances raise substantial doubt about our ability to continue as a

going concern for a period of one year from the date that the consolidated financial statements included elsewhere in this Annual Report

on Form 10-K are issued.

Implementation of our plans and our ability to continue as a going concern will depend upon our ability to develop

PV-10 and PH-10, and to raise additional capital.

believes that we may have access to capital resources through possible public or private equity offerings, including the 2021

Financing, exchange offers, debt financings, corporate collaborations or other means.

If we are unable to raise sufficient capital, we

will not be able to pay our obligations as they become due.

investigational drug product candidates are at an early to mid-stage of development and may never obtain U.S.

or international

regulatory approvals required for us to commercialize our investigational drug product candidates.

or international regulatory

approvals required for us to commercialize our investigational drug product candidates.

will need approval of the FDA to commercialize our investigational drug product candidates in the U.S.

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regulatory authorities in international jurisdictions to commercialize our investigational drug product candidates there.

are continuing to pursue clinical development of our most advanced drug product candidates, PV-10 and PH-10, for use as treatments

for specific disease indications.

The continued and further development of these drug product candidates will require significant

additional research, formulation and manufacturing development, and pre-clinical and extensive clinical testing prior to their

regulatory approval and commercialization.

Pre-clinical and clinical studies of our drug product candidates may not demonstrate

the safety and efficacy necessary to obtain regulatory approvals.

Pharmaceutical and biotechnology companies have suffered significant

setbacks in advanced clinical trials, even after experiencing promising results in earlier trials.

Pharmaceutical products that

appear to be promising at early stages of development may not reach the market or be marketed successfully for a number of reasons,

including a product may be found to be ineffective or have harmful side effects during subsequent pre-clinical testing or clinical

trials, a product may fail to receive necessary regulatory clearance, a product may be too difficult to manufacture on a large

scale, a product may be too expensive to manufacture or market, a product may not achieve broad market acceptance, others may

hold proprietary rights that will prevent a product from being marketed, and others may market equivalent or superior products.

of the FDA’s regulatory requirements typically takes many years, depends upon the type, complexity and novelty of the product

candidate and requires substantial resources for research, development and testing.

We cannot predict whether our research and

clinical approaches will result in drugs that the FDA considers safe for humans and effective for indicated uses.

substantial discretion in the drug approval process and may require us to conduct additional nonclinical and clinical testing

or to perform post-marketing studies.

The approval process may also be delayed by changes in government regulation, future legislation

or administrative action or changes in FDA policy that occur prior to or during our regulatory review.

Delays in obtaining regulatory

approvals may delay commercialization of, and our ability to derive revenues from, our prescription drug candidates, impose costly

procedures on us, and diminish any competitive advantages that we may otherwise enjoy.

research and product development efforts may not be successfully completed and may not result in any successfully commercialized

drug products.

Further, after commercial introduction of a new drug product, discovery of problems through adverse event reporting

could result in restrictions on the product, including withdrawal from the market and, in certain cases, civil or criminal penalties.

if we comply with all FDA requests, we cannot be sure that we will ever obtain regulatory clearance for any of our drug product

Failure to obtain FDA approval of any of our prescription drug candidates will severely undermine our business by

reducing our number of salable drug products and, therefore, corresponding revenues.

international jurisdictions, we must receive approval from the appropriate regulatory authorities before we can commercialize

our prescription drug candidates.

International regulatory approval processes generally include all of the risks associated with

the FDA approval procedures described above.

obtaining regulatory approval for the sale of our drug product candidates, including PV-10 and PH-10, we must conduct additional

clinical trials to demonstrate the safety and efficacy of our drug product candidates.

Clinical testing is expensive, difficult

to design and implement, can take many years to complete and is uncertain as to timing and outcome.

Competition in clinical development

has made it difficult to enroll patients at an acceptable rate in some of our clinical trials.

Advances in medical technology

could make our prescription drug candidates obsolete prior to completion of clinical testing.

A failure of one or more of our

clinical trials may occur at any stage of testing.

The outcome of pre-clinical testing and early clinical trials may not be predictive

of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results.

pre-clinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed

their product candidates performed satisfactorily in pre-clinical studies and clinical trials have nonetheless failed to obtain

marketing approval for their products.

Product candidates in later stages of clinical trials may fail to show the desired safety

and efficacy characteristics despite having progressed satisfactorily through pre-clinical studies and initial clinical testing.

A number of companies in the pharmaceutical and biotechnology industries, including those with greater resources and experience,

have suffered significant setbacks in Phase 3 clinical development, even after seeing promising results in earlier clinical trials.

research and development expenses may increase in connection with expanding clinical trials of our product candidates in existing

indications and undertaking clinical trials of our product candidates in new indications.

Because successful development of our

drug product candidates is uncertain, we are unable to estimate the actual funds required to complete research and development

and commercialize our products under development.

or inconclusive results of our future clinical trials of PV-10 and PH-10, or any other clinical trial we conduct, could cause

the FDA to require that we repeat or conduct additional clinical studies.

Despite the results reported in earlier clinical trials

for PV-10 and PH-10, we do not know whether any clinical trials we may conduct will demonstrate adequate efficacy and safety to

result in regulatory approval to market our product candidates.

If later stage clinical trials do not produce favorable results,

our ability to obtain regulatory approval for our product candidates, may be adversely impacted.

in clinical trials are common and have many causes, and any delay could result in increased costs to us and jeopardize or delay

our ability to obtain regulatory approval.

planned or ongoing clinical trials may not begin on time, have an effective design, enroll a sufficient number of subjects, or

be completed on schedule, if at all.

Events which may result in delays or unsuccessful completion of clinical trials, including

our future clinical trials, include inability to raise funding, initiate or continue a trial, delays in obtaining regulatory approval

to commence a trial, delays in reaching agreement with the FDA or other regulatory authorities on final trial design, imposition

of a clinical hold following an inspection of our clinical trial operations or trial sites by the FDA or other regulatory authorities,

delays in reaching agreement on acceptable terms with prospective contract research organizations (“CROs”) and clinical

trial sites, delays in obtaining required institutional review board (“IRB”) approval at each site, delays in recruiting

suitable patients to participate in a trial, delays in having subjects complete participation in a trial or return for post-treatment

follow-up, delays caused by subjects dropping out of a trial, delays caused by clinical sites dropping out of a trial, time required

to add new clinical sites or to obtain regulatory approval and open sites in geographic regions beyond the sites initially planned,

and delays by our contract manufacturers to produce and deliver sufficient supply of clinical trial materials.

addition, we may experience a number of unforeseen events during clinical trials for our prescription drug candidates, including

PV-10 and PH-10, that could delay or prevent the commencement and/or completion of our clinical trials, including regulators or

institutional review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial

at a prospective trial site, the clinical study protocol may require one or more amendments delaying study completion, clinical

trials of our product candidates may produce negative or inconclusive results, and we may decide, or regulators may require us

to conduct additional clinical trials or abandon product development programs, the number of subjects required for clinical trials

of our product candidates may be larger than we anticipate, subjects may drop out of these clinical trials at a higher rate than

we anticipate and enrollment in these clinical trials may be significantly slower than we anticipated requiring us to expand the

geographic scope of enrollment of patients, clinical investigators or study subjects may fail to comply with clinical study protocols,

trial conduct and data analysis errors may occur, including, but not limited to, data entry and/or processing errors, our third-party

contractors may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or

at all, we might have to suspend or terminate clinical trials of our prescription drug candidates for various reasons, including

a finding that the subjects are being exposed to unacceptable health risks, regulators or institutional review boards may require

that we or our investigators suspend or terminate clinical research for various reasons, including noncompliance with regulatory

requirements, the cost of clinical trials of our prescription drug candidates may be greater than we anticipate, the supply or

quality of our clinical trial materials or other materials necessary to conduct clinical trials of our prescription drug candidates

may be insufficient or inadequate, and our prescription drug candidates may have undesirable side effects or other unexpected

are continuing to pursue clinical development of our most advanced drug product candidates, PV-10 and PH-10, for use as treatments for

specific disease indications.

The continued and further development of these drug product candidates will require significant additional

research, formulation and manufacturing development, and pre-clinical and extensive clinical testing prior to their regulatory approval

and commercialization.

Pre-clinical and clinical studies of our drug product candidates may not demonstrate the safety and efficacy necessary

to obtain regulatory approvals.

Pharmaceutical and biotechnology companies have suffered significant setbacks in advanced clinical trials,

even after experiencing promising results in earlier trials.

Pharmaceutical products that appear to be promising at early stages of development

may not reach the market or be marketed successfully for a number of reasons, including a product may be found to be ineffective or have

harmful side effects during subsequent pre-clinical testing or clinical trials, a product may fail to receive necessary regulatory clearance,

a product may be too difficult to manufacture on a large scale, a product may be too expensive to manufacture or market, a product may

not achieve broad market acceptance, others may hold proprietary rights that will prevent a product from being marketed, and others may

market equivalent or superior products.

of the FDA’s regulatory requirements typically takes many years, depends upon the type, complexity and novelty of the product candidate

and requires substantial resources for research, development, and testing.

We cannot predict whether our research and clinical

approaches will result in drugs that the FDA considers safe for humans and effective for indicated uses.

The FDA has substantial discretion

in the drug approval process and may require us to conduct additional nonclinical and clinical testing or to perform post-marketing studies.

The approval process may also be delayed by changes in government regulation, future legislation or administrative action or changes

in FDA policy that occur prior to or during our regulatory review.

Delays in obtaining regulatory approvals may delay commercialization

of, and our ability to derive revenues from, our prescription drug candidates, impose costly procedures on us, and diminish any competitive

advantages that we may otherwise enjoy.

research and product development efforts may not be successfully completed and may not result in any successfully commercialized drug

Further, after commercial introduction of a new drug product, discovery of problems through adverse event reporting could result

in restrictions on the product, including withdrawal from the market and, in certain cases, civil or criminal penalties.

if we comply with all FDA requests, we cannot be sure that we will ever obtain regulatory clearance for any of our drug product candidates.

Failure to obtain FDA approval of any of our prescription drug candidates will severely undermine our business by reducing our number

of salable drug products and, therefore, corresponding revenues.

international jurisdictions, we must receive approval from the appropriate regulatory authorities before we can commercialize our prescription

drug candidates.

International regulatory approval processes generally include all of the risks associated with the FDA approval procedures

described above.

obtaining regulatory approval for the sale of our drug product candidates, including PV-10 and PH-10, we must conduct additional clinical

trials to demonstrate the safety and efficacy of our drug product candidates.

Clinical testing is expensive, difficult to design and

implement, can take many years to complete and is uncertain as to timing and outcome.

Competition in clinical development has made it

difficult to enroll patients at an acceptable rate in some of our clinical trials.

Advances in medical technology could make our prescription

drug candidates obsolete prior to completion of clinical testing.

A failure of one or more of our clinical trials may occur at any stage

The outcome of pre-clinical testing and early clinical trials may not be predictive of the success of later clinical trials,

and interim results of a clinical trial do not necessarily predict final results.

Moreover, pre-clinical and clinical data are often

susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily

in pre-clinical studies and clinical trials have nonetheless failed to obtain marketing approval for their products.

Product candidates

in later stages of clinical trials may fail to show the desired safety and efficacy characteristics despite having progressed satisfactorily

through pre-clinical studies and initial clinical testing.

A number of companies in the pharmaceutical and biotechnology industries,

including those with greater resources and experience, have suffered significant setbacks in Phase 3 clinical development, even after

seeing promising results in earlier clinical trials.

research and development expenses may increase in connection with expanding clinical trials of our product candidates in existing indications

and undertaking clinical trials of our product candidates in new indications.

Because successful development of our drug product candidates

is uncertain, we are unable to estimate the actual funds required to complete research and development and commercialize our products

under development.

or inconclusive results of our future clinical trials of PV-10 and PH-10, or any other clinical trial we conduct, could cause the FDA

to require that we repeat or conduct additional clinical studies.

Despite the results reported in earlier clinical trials for PV-10 and

PH-10, we do not know whether any clinical trials we may conduct will demonstrate adequate efficacy and safety to result in regulatory

approval to market our product candidates.

If later stage clinical trials do not produce favorable results, our ability to obtain regulatory

approval for our product candidates, may be adversely impacted.

in clinical trials are common and have many causes, and any delay could result in increased costs to us and jeopardize or delay our ability

to obtain regulatory approval.

planned or ongoing clinical trials may not begin on time, have an effective design, enroll a sufficient number of subjects, or be completed

on schedule, if at all.

Events which may result in delays or unsuccessful completion of clinical trials, including our future clinical

trials, include inability to raise funding, initiate or continue a trial, delays in obtaining regulatory approval to commence a trial,

delays in reaching agreement with the FDA or other regulatory authorities on final trial design, imposition of a clinical hold following

an inspection of our clinical trial operations or trial sites by the FDA or other regulatory authorities, delays in reaching agreement

on acceptable terms with prospective contract research organizations (“CROs”) and clinical trial sites, delays in obtaining

required institutional review board (“IRB”) approval at each site, delays in recruiting suitable patients to participate

in a trial, delays in having subjects complete participation in a trial or return for post-treatment follow-up, delays caused by subjects

dropping out of a trial, delays caused by clinical sites dropping out of a trial, time required to add new clinical sites or to obtain

regulatory approval and open sites in geographic regions beyond the sites initially planned, and delays by our contract manufacturers

to produce and deliver sufficient supply of clinical trial materials.

addition, we may experience a number of unforeseen events during clinical trials for our prescription drug candidates, including PV-10

and PH-10, that could delay or prevent the commencement and/or completion of our clinical trials, including regulators or institutional

review boards may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial

site, the clinical study protocol may require one or more amendments delaying study completion, clinical trials of our product candidates

may produce negative or inconclusive results, and we may decide, or regulators may require us to conduct additional clinical trials or

abandon product development programs, the number of subjects required for clinical trials of our product candidates may be larger than

we anticipate, subjects may drop out of these clinical trials at a higher rate than we anticipate and enrollment in these clinical trials

may be significantly slower than we anticipated requiring us to expand the geographic scope of enrollment of patients, clinical investigators

or study subjects may fail to comply with clinical study protocols, trial conduct and data analysis errors may occur, including, but

not limited to, data entry and/or processing errors, our third-party contractors may fail to comply with regulatory requirements or meet

their contractual obligations to us in a timely manner, or at all, we might have to suspend or terminate clinical trials of our prescription

drug candidates for various reasons, including a finding that the subjects are being exposed to unacceptable health risks, regulators

or institutional review boards may require that we or our investigators suspend or terminate clinical research for various reasons, including

noncompliance with regulatory requirements, the cost of clinical trials of our prescription drug candidates may be greater than we anticipate,

the supply or quality of our clinical trial materials or other materials necessary to conduct clinical trials of our prescription drug

candidates may be insufficient or inadequate, and our prescription drug candidates may have undesirable side effects or other unexpected

characteristics, causing us or our investigators to suspend or terminate the trials.

we or the FDA may suspend our clinical trials at any time if it appears we are exposing participants to unacceptable health risks

or if the FDA finds deficiencies in our submissions or the conduct of these trials.

If initiation or completion of any of our

clinical trials for our product candidates, are delayed for any of the above reasons or other reasons, our development costs may

increase, the approval process could be delayed, any periods during which we may have the exclusive right to commercialize our

prescription drug candidates may be reduced and our competitors may bring drug products to market before us.

Any of these events

could impair our ability to generate revenues from drug product sales and impair our ability to generate regulatory and commercialization

milestones and royalties, all of which could have a material adverse effect on our business.

we or the FDA may suspend our clinical trials at any time if it appears we are exposing participants to unacceptable health risks or

if the FDA finds deficiencies in our submissions or the conduct of these trials.

If initiation or completion of any of our clinical trials

for our product candidates, are delayed for any of the above reasons or other reasons, our development costs may increase, the approval

process could be delayed, any periods during which we may have the exclusive right to commercialize our prescription drug candidates

may be reduced and our competitors may bring drug products to market before us.

Any of these events could impair our ability to generate

revenues from drug product sales and impair our ability to generate regulatory and commercialization milestones and royalties, all of

which could have a material adverse effect on our business.

results of our clinical trials may not support acceptable label claims concerning our prescription drug candidates.

if our clinical trials are completed as planned, we cannot be certain that their results will support acceptable label claims

concerning our drug product candidates.

Success in pre-clinical testing and early clinical trials does not ensure that later clinical

trials will be successful, and we cannot be sure that the results of later clinical trials will replicate the results of prior

clinical trials and pre-clinical testing.

The clinical trial process may fail to demonstrate that our prescription drug candidates

are safe for humans or effective for indicated uses.

if our clinical trials are completed as planned, we cannot be certain that their results will support acceptable label claims concerning

our drug product candidates.

Success in pre-clinical testing and early clinical trials does not ensure that later clinical trials will

be successful, and we cannot be sure that the results of later clinical trials will replicate the results of prior clinical trials and

pre-clinical testing.

The clinical trial process may fail to demonstrate that our prescription drug candidates are safe for humans or

effective for indicated uses.

failure could cause us to abandon a prescription drug candidate and may delay development of other prescription drug candidates.

Any delay in, or termination of, our clinical trials will delay our ability to commercialize our prescription drug candidates

and generate product revenues.

delay in, or termination of, our clinical trials will delay our ability to commercialize our prescription drug candidates and generate

product revenues.

In addition, we anticipate that our clinical trials will involve only a small patient population.

Accordingly, the results of such trials may not be indicative of future results over a larger patient population.

Accordingly, the

results of such trials may not be indicative of future results over a larger patient population.

and patients may not accept and use our prescription drug candidates.

if the FDA approves our drug product candidates, physicians and patients may not accept and use them.

Acceptance and use of our

drug products will depend upon a number of factors including perceptions by members of the healthcare community, including physicians,

about the safety and effectiveness of our drug products, availability of reimbursement for our drug products from government or

other healthcare payers, and effectiveness of marketing and distribution efforts by us and our licensees and distributors, if

we expect sales or licensure of our prescription drug candidates, if approved, to generate substantially all of our revenues for

the foreseeable future, the failure of any of these drugs to find market acceptance would harm our business and could require

us to seek additional financing.

Acceptance and use of our drug

products will depend upon a number of factors including perceptions by members of the healthcare community, including physicians, about

the safety and effectiveness of our drug products, availability of reimbursement for our drug products from government or other healthcare

payers, and effectiveness of marketing and distribution efforts by us and our licensees and distributors, if any.

we expect sales or licensure of our prescription drug candidates, if approved, to generate substantially all of our revenues if they

are approved, the failure of any of these drugs to find market acceptance would harm our business and could require us to seek additional

have no sales, marketing or distribution capabilities for our prescription drug candidates.

currently have no sales, marketing or distribution capabilities.

Our future success depends, in part, on our ability to enter

into and maintain collaborative relationships, the collaborator’s strategic interest in the prescription drug products under

development and such collaborator’s ability to successfully market and sell any such drug products.

There can be no assurance

that we will be able to establish or maintain relationships with third party collaborators or develop in-house sales and distribution

capabilities.

To the extent that we depend on third parties for marketing and distribution, any revenues we receive will depend

upon the efforts of such third parties, and there can be no assurance that such efforts will be successful.

In addition, there

can also be no assurance that we will be able to market and sell our prescription drug candidates in the U.S.

Our future success depends, in part, on our ability to enter into and

maintain collaborative relationships, the collaborator’s strategic interest in the prescription drug products under development

and such collaborator’s ability to successfully market and sell any such drug products.

There can be no assurance that we will

be able to establish or maintain relationships with third party collaborators or develop in-house sales and distribution capabilities.

To the extent that we depend on third parties for marketing and distribution, any revenues we receive will depend upon the efforts of

such third parties, and there can be no assurance that such efforts will be successful.

In addition, there can also be no assurance that

we will be able to market and sell our prescription drug candidates in the U.S.

or internationally.

in the prescription pharmaceutical and biotechnology industries is intense.

pharmaceutical and biotechnology companies and research organizations currently engage in or have in the past engaged in research

efforts related to treatment of cancer and dermatological conditions, which may compete with our clinical trials for patients

and investigator resources, cause lower enrollment than anticipated, and could lead to the development of drug products or treatment

therapies that could compete directly with our drug product candidates that we are seeking to develop and market.

pharmaceutical and biotechnology companies and research organizations currently engage in or have in the past engaged in research efforts

related to treatment of cancer and dermatological conditions, which may compete with our clinical trials for patients and investigator

resources, cause lower enrollment than anticipated, and could lead to the development of drug products or treatment therapies that could

compete directly with our drug product candidates that we are seeking to develop and market.

companies are also developing novel therapies to treat cancer and dermatological conditions and, in this regard, are our competitors.

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that may compete with our efforts to establish similar collaborative arrangements.

Academic institutions, government agencies,

and other public and private research organizations may also conduct research, seek patent protection, and establish collaborative

arrangements for research, clinical development, and marketing of prescription drug candidates similar to ours.

These companies

and institutions compete with us in recruiting and retaining qualified scientific and management personnel as well as in acquiring

technologies complementary to our drug development programs.

addition to the above factors, we expect to face competition in product efficacy and safety, the timing and scope of regulatory

consents, availability of resources, reimbursement coverage, price, and patent position, including potentially dominant patent

positions of others.

our prescription drug candidates PV-10 and PH-10 have not yet been approved by the FDA or introduced to the marketplace, we cannot

estimate what competition these prescription drug candidates might face when they are finally introduced, if at all.

assure you that these prescription drug candidates will not face significant competition for other approved drug products, investigational

drug products, and generic equivalents.

Academic institutions, government agencies, and other

public and private research organizations may also conduct research, seek patent protection, and establish collaborative arrangements

for research, clinical development, and marketing of prescription drug candidates similar to ours.

These companies and institutions compete

with us in recruiting and retaining qualified scientific and management personnel as well as in acquiring technologies complementary

to our drug development programs.

addition to the above factors, we expect to face competition in product efficacy and safety, the timing and scope of regulatory consents,

availability of resources, reimbursement coverage, price, and patent position, including potentially dominant patent positions of others.

our prescription drug candidates PV-10 and PH-10 have not yet been approved by the FDA or introduced to the marketplace, we cannot estimate

what competition these prescription drug candidates might face when they are finally introduced, if at all.

We cannot assure you that

these prescription drug candidates will not face significant competition for other approved drug products, investigational drug products,

and generic equivalents.

we lose any of our key personnel, we may be unable to successfully execute our business plan.

business is presently managed by key employees, independent contractors, and Board members:

(i) Bruce Horowitz, our COO, who is an independent

contractor, (ii) Heather Raines, CPA, our CFO, (iii) Dominic Rodrigues, who is vice chair of the Board, and (iv) Eric Wachter, Ph.D.,

our Chief Technology Officer (“CTO”).

order to successfully execute our business plan, our management and Board must succeed in all of the following critical areas:

diseases and possible therapies in the areas of oncology and dermatology, developing our prescription drugs candidates, marketing and

selling developed prescription drug candidates, obtaining additional capital to finance research and development production, and marketing

of our drug products, and managing our business as it grows.

resulting from management transition may have a detrimental impact on our ability to implement our strategy.

The reduction in role and/or

loss of key employees, contractors, and/or Board members could have a material adverse effect on our operations, and limit or constrain

our ability to execute our business plan.

business and operations are subject to risks related to climate change.

long-term effects of global climate change present risks to our business.

Extreme weather or other conditions caused by climate change

could adversely impact our supply chain and the operation of our business.

Such conditions could also result in physical damage to our

leased property, clinical trial materials, clinical sites, or the facilities of our contract manufacturers.

These events could adversely

affect our operations and our financial performance.

Our business and operations are vulnerable to computer system

failures, cyber-attacks or deficiencies in our cyber-security, which could increase our expenses, divert the attention of our management

and key personnel away from our business operations and adversely affect our results of operations.

Despite the implementation of security measures, our internal computer

systems, and those of third parties on which we rely, are vulnerable to damage from:

computer viruses;

natural disasters;

telecommunication and electrical failures;

cyber-attacks or cyber-intrusions over the Internet;

attachments to emails;

persons inside

our organization;

or persons with access to systems inside our organization.

The risk of a security breach or disruption, particularly

through cyber-attacks or cyber intrusion, including by computer hackers, foreign governments, and cyber terrorists, has generally increased

as the number, intensity and sophistication of attempted attacks and intrusions from around the world have increased.

If such an event

were to occur and cause interruptions in our operations, it could result in a material disruption of our product development programs.

For example, the loss of clinical trial data from completed or ongoing or planned clinical trials could result in delays in our regulatory

approval efforts and significantly increase our costs to recover or reproduce the data.

To the extent that any disruption or security

breach was to result in a loss of or damage to our data or applications, or inappropriate disclosure of confidential or proprietary information,

we could incur material legal claims and liability, and damage to our reputation, and the further development of our product candidates

could be delayed.

We could be forced to expend significant resources in response to a cyber security breach, including repairing system

damage, increasing cyber security protection costs by deploying additional personnel and protection technologies, paying regulatory fines

and resolving legal claims and regulatory actions, all of which would increase our expenses, divert the attention of our management and

key personnel away from our business operations and adversely affect our results of operations.

Related to Our Intellectual Property

we are unable to secure or enforce patent rights, trademarks, trade secrets or other IP, our business could be harmed.

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we develop or license.

In addition, our competitors may develop prescription drug candidates similar to ours using methods and

technologies that are beyond the scope of our IP protection, which could reduce our anticipated sales.

While some of our drug

product candidates have proprietary patent protection, a challenge to these patents can subject us to expensive litigation.

concerning patents, other forms of IP, and proprietary technology is becoming more widespread and can be protracted and expensive

and can distract management and other personnel from performing product development duties.

also rely upon trade secrets, unpatented proprietary know-how, and continuing technological innovation to develop a competitive

We cannot assure you that others will not independently develop substantially equivalent proprietary technology and

techniques or otherwise gain access to our trade secrets and technology, or that we can adequately protect our trade secrets and

In addition, our competitors may develop prescription drug candidates similar to ours using methods and technologies

that are beyond the scope of our IP protection, which could reduce our anticipated sales.

While some of our drug product candidates have

proprietary patent protection, a challenge to these patents can subject us to expensive litigation.

Litigation concerning patents, other

forms of IP, and proprietary technology is becoming more widespread and can be protracted and expensive and can distract management and

other personnel from performing product development duties.

also rely upon trade secrets, unpatented proprietary knowledge and continuing technological innovation to develop a competitive

We cannot assure you that others will not independently develop substantially equivalent proprietary technology and techniques

or otherwise gain access to our trade secrets and technology, or that we can adequately protect our trade secrets and technology.

we are unable to secure or enforce patent rights, trademarks, trade secrets, or other IP, our business, financial condition, results

of operations and cash flows could be materially adversely affected.

If we infringe on the IP of others, our business could be

could be sued for infringing patents and other IP that purportedly cover prescription drug candidates and/or methods of using

such prescription drug candidates held by persons other than us.

Litigation arising from an alleged infringement could result

in removal from the market, or a substantial delay in, or prevention of, the introduction of our prescription drug candidates,

any of which could have a material adverse effect on our business, financial condition, results of operations, and cash flows.

If we infringe on the IP of others, our business could be harmed.

could be sued for infringing patents and other IP that purportedly cover prescription drug candidates and/or methods of using such prescription

drug candidates held by persons other than us.

Litigation arising from an alleged infringement could result in removal from the market,

or a substantial delay in, or prevention of, the introduction of our prescription drug candidates, any of which could have a material

adverse effect on our business, financial condition, results of operations, and cash flows.

we do not update and enhance our technologies, they will become obsolete.

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and commercialize those products.

While we believe that our current technology is adequate for our present needs, if we fail to

stay at the forefront of technological development, we will be unable to compete effectively.

Our competitors may use greater

resources to develop new pharmaceutical technologies and to commercialize products based on those technologies.

Accordingly, our

technologies may be rendered obsolete by advances in existing technologies or the development of different technologies by one

or more of our current or future competitors.

we lose any of our key personnel, we may be unable to successfully execute our business plan.

business is presently managed by key employees, independent contractors, and Board members:

(i) Bruce Horowitz, our COO, who is

an independent contractor, (ii) Heather Raines, CPA, our CFO, (iii) Dominic Rodrigues, who is vice chair of the Board, and (iv)

Eric Wachter, Ph.D., our Chief Technology Officer (“CTO”).

order to successfully execute our business plan, our management and Board must succeed in all of the following critical areas:

researching diseases and possible therapies in the areas of oncology and dermatology, developing our prescription drugs candidates,

marketing and selling developed prescription drug candidates, obtaining additional capital to finance research and development

production, and marketing of our drug products, and managing our business as it grows.

resulting from management transition may have a detrimental impact on our ability to implement our strategy.

The reduction in

role and/or loss of key employees, contractors, and/or Board members could have a material adverse effect on our operations, and

limit or constrain our ability to execute our business plan.

While we believe that our current technology is adequate for our present needs, if we fail to stay

at the forefront of technological development, we will be unable to compete effectively.

Our competitors may use greater resources to

develop new pharmaceutical technologies and to commercialize products based on those technologies.

Accordingly, our technologies may

be rendered obsolete by advances in existing technologies or the development of different technologies by one or more of our current

or future competitors.

Risks Related to Our Governing Documents and

Anti-takeover

provisions in our organizational documents and Delaware law may discourage or prevent a change of control, even if an acquisition

would be beneficial to our stockholders, which could affect our stock price adversely and prevent attempts by our stockholders

to replace or remove our current management.

provisions in our organizational documents and Delaware law may discourage or prevent a change of control, even if an acquisition would

be beneficial to our stockholders, which could affect our stock price adversely and prevent attempts by our stockholders to replace or

remove our current management.

certificate of incorporation and bylaws contain provisions that could delay or prevent a change of control of our company or changes

in our board of directors that our stockholders might consider favorable.

Among other things, these provisions will (i) permit

our Board to issue up to 25,000,000 shares of preferred stock which can be created and issued by the Board without prior stockholder

approval, with rights senior to those of the common stock, (ii) provide that all vacancies on our Board, including as a result

of newly created directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors

then in office, even if less than a quorum, (iii) require that any action to be taken by our stockholders must be affected at

a duly called annual or special meeting of stockholders and not be taken by written consent, (iv) provide that stockholders seeking

to present proposals before a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders

must provide advance notice in writing, and also specify requirements as to the form and content of a stockholder’s notice,

(v) not provide for cumulative voting rights, thereby allowing the holders of a majority of the shares of common stock entitled

to vote in any election of directors to elect all of the directors standing for election, and (vi) provide that special meetings

of our stockholders may be called only by the Board or by such person or persons requested by a majority of the Board to call

such meetings.

and other provisions in our certificate of incorporation, bylaws and Delaware law could make it more difficult for stockholders

or potential acquirers to obtain control of our Board or initiate actions that are opposed by our then-current Board, including

delaying or impeding a merger, tender offer, or proxy contest involving our company.

Any delay or prevention of a change of control

transaction or changes in our Board could cause the market price of our common stock to decline.

stock price is below $5.00 per share and is treated as a “penny stock,”

which places restrictions on broker-dealers

recommending the stock for purchase.

common stock is defined as “penny stock”

under the Exchange Act and its rules.

The SEC has adopted regulations that

define “penny stock”

to include common stock that has a market price of less than $5.00 per share, subject to certain

Among other things, these provisions will (i) permit our Board

to issue up to 25,000,000 shares of preferred stock which can be created and issued by the Board without prior stockholder approval,

with rights senior to those of the common stock, (ii) provide that all vacancies on our Board, including as a result of newly created

directorships, may, except as otherwise required by law, be filled by the affirmative vote of a majority of directors then in office,

even if less than a quorum, (iii) require that any action to be taken by our stockholders must be affected at a duly called annual or

special meeting of stockholders and not be taken by written consent, (iv) provide that stockholders seeking to present proposals before

a meeting of stockholders or to nominate candidates for election as directors at a meeting of stockholders must provide advance notice

in writing, and also specify requirements as to the form and content of a stockholder’s notice, (v) not provide for cumulative

voting rights, and (vi) provide that special meetings of our stockholders may be called only by

the Board or by such person or persons requested by a majority of the Board to call such meetings.

and other provisions in our certificate of incorporation, bylaws and Delaware law could make it more difficult for stockholders or potential

acquirers to obtain control of our Board or initiate actions that are opposed by our then-current Board, including delaying or impeding

a merger, tender offer, or proxy contest involving our company.

Any delay or prevention of a change of control transaction or changes

in our Board could cause the market price of our common stock to decline.

stock price is below $5.00 per share and is treated as a “penny stock,” which places restrictions on broker-dealers recommending

the stock for purchase.

common stock is defined as “penny stock” under the Exchange Act and its rules.

The SEC has adopted regulations that define

“penny stock” to include common stock that has a market price of less than $5.00 per share, subject to certain exceptions.

These rules include the following requirements:

(i) broker-dealers must deliver, prior to the transaction, a disclosure

schedule prepared by the SEC relating to the penny stock market, (ii) broker-dealers must disclose the commissions payable to

the broker-dealer and its registered representative, (iii) broker-dealers must disclose current quotations for the securities,

and (iv) a broker-dealer must furnish its customers with monthly statements disclosing recent price information for all penny

stocks held in the customer’s account and information on the limited market in penny stocks.

sales practice requirements are imposed on broker-dealers who sell penny stocks to persons other than established customers and

accredited investors.

For these types of transactions, the broker-dealer must make a special suitability determination for the

purchaser and must have received the purchaser’s written consent to the transaction prior to sale.

If our common stock remains

subject to these penny stock rules these disclosure requirements may have the effect of reducing the level of trading activity

in the secondary market for our common stock.

As a result, fewer broker-dealers may be willing to make a market in our stock,

which could affect a shareholder’s ability to sell their shares.

(i) broker-dealers must deliver, prior to the transaction, a disclosure schedule prepared

by the SEC relating to the penny stock market, (ii) broker-dealers must disclose the commissions payable to the broker-dealer and its

registered representative, (iii) broker-dealers must disclose current quotations for the securities, and (iv) a broker-dealer must furnish

its customers with monthly statements disclosing recent price information for all penny stocks held in the customer’s account and

information on the limited market in penny stocks.

sales practice requirements are imposed on broker-dealers who sell penny stocks to persons other than established customers and accredited

For these types of transactions, the broker-dealer must make a special suitability determination for the purchaser and must

have received the purchaser’s written consent to the transaction prior to sale.

If our common stock remains subject to these penny

stock rules these disclosure requirements may have the effect of reducing the level of trading activity in the secondary market for our

common stock.

As a result, fewer broker-dealers may be willing to make a market in our stock, which could affect a shareholder’s

ability to sell their shares.

sales by our stockholders may adversely affect our stock price and our ability to raise funds in new stock offerings.

of our common stock in the public market following any prospective offering could lower the market price of our common stock.

Sales may also make it more difficult for us to sell equity securities or equity-related securities in the future at a time and

price that our management deems acceptable.

also make it more difficult for us to sell equity securities or equity-related securities in the future at a time and price that our

management deems acceptable.

is our general policy to retain any earnings for use in our operation.

have never declared or paid cash dividends on our common stock.

We currently intend to retain all of our future earnings, if any,

for use in our business and therefore do not anticipate paying any cash dividends on our common stock in the foreseeable future,

although we intend to issue shares of common stock in satisfaction of the dividend payments due on our Series B Preferred Stock.

the event of the sale, liquidation or dissolution of the Company or any of our assets, holders of shares of a yet-to-be designated

Series D Preferred Stock will be entitled to a preference of a multiple of their investment amount, which will reduce the proceeds

to be received by holders of our common stock.

connection with the 2017 Financing and 2020 Financing, we have issued convertible notes that will become convertible into shares

of a yet-to-be designated Series D Preferred Stock.

The Series D Preferred Stock will have a first priority right to receive proceeds

from the sale, liquidation or dissolution of us or any of our assets (each, a “Company Event”).

If a Company Event

occurs within two (2) years of the date of issuance of the Series D Preferred Stock (the “Date of Issuance”), the

holders of Series D Preferred Stock will receive a preference of four times (4x) their respective investment amount.

Event occurs after the second (2nd) anniversary of the Date of Issuance, the holders of the Series D Preferred Stock will receive

a preference of six times (6x) their respective investment amount.

As a result, upon the occurrence of a Company Event, the holders

of Series D Preferred Stock would have the right to receive proceeds from any such transaction before our common stockholders.

The payment of this preference could result in our common stockholders not receiving any consideration in connection with a Company

of SARS-CoV-2.

We currently intend to retain all of our future earnings, if any, for

use in our business and therefore do not anticipate paying any cash dividends on our common stock in the foreseeable future.

the event of the liquidation, winding-up or dissolution of the Company or certain mergers, corporate reorganizations or sales

of our assets, holders of Series D and Series D-1 Preferred Stock will be entitled to a preference of a multiple of their investment

amount, which will reduce the proceeds to be received by holders of our common stock.

connection with the 2021, 2020 and 2017 Financings, we have issued convertible notes that converted or are convertible into shares of

Series D and Series D-1 Preferred Stock.

The Series D and Series D-1 Preferred Stock will have a first priority right to receive proceeds

from the liquidation, winding-up or dissolution of us or certain mergers, corporate reorganizations or sales of our assets (each, a “Company Event”).

If a Company Event occurs within two (2) years of the

date of issuance of the Series D and Series D-1 Preferred Stock (the “Date of Issuance”), the holders of Series D

and Series D-1 Preferred Stock will receive a preference of four times (4x) their respective investment amount.

If a Company Event occurs

after the second (2nd) anniversary of the Date of Issuance, the holders of the Series D and Series D-1 Preferred Stock will receive a

preference of six times (6x) their respective investment amount.

As a result, upon the occurrence of a Company Event, the holders of

Series D and Series D-1 Preferred Stock would have the right to receive proceeds from any such transaction before our common stockholders.

The payment of this preference could result in our common stockholders not receiving any consideration in connection with a Company Event.

Related to SARS-CoV-2

are subject to risks associated with a pandemic, epidemic or outbreak of a contagious disease, such as the ongoing SARS-CoV-2 pandemic,

which may affect our future access to liquidity and materially adversely affect our business operations, results of operations and financial

was reportedly first identified in late-2019 and subsequently declared a global pandemic by the World Health Organization on March 11,

As a result of the SARS-CoV-2 pandemic, many companies have experienced disruptions of their operations and the markets

The Company has taken several temporary precautionary measures intended to help ensure the well-being of its employees

and contractors and to minimize business disruption.

The Company considered the impact of SARS-CoV-2 pandemic on its business

and operational assumptions and estimates, and determined there were no material adverse impacts on the Company’s results

of operations and financial position at December 31, 2020.

full extent of the SARS-CoV-2 pandemic impacts on the Company’s operations and financial condition is uncertain.

has experienced slower than normal enrollment and treatment of patients, and a prolonged SARS-CoV-2 pandemic could have a material

adverse impact on the Company’s business and financial results, including the timing and ability of the Company to raise

capital, initiate and/or complete current and/or future preclinical studies and/or clinical trials;

disrupt the Company’s

regulatory activities;

and/or have other adverse effects on the Company’s clinical development.

As a result of the SARS-CoV-2 pandemic, many companies have experienced disruptions of their operations and the markets they serve.

The Company has taken several temporary precautionary measures intended to help ensure the well-being of its employees and contractors

and to minimize business disruption.

The Company considered the impact of SARS-CoV-2 pandemic on its business and operational assumptions

and estimates, and determined there were no material adverse impacts on the Company’s results of operations and financial position

at December 31, 2021.

full extent of the SARS-CoV-2 pandemic impacts on the Company’s operations and financial condition is still uncertain.

Company has experienced slower than normal enrollment and treatment of patients, and a prolonged SARS-CoV-2 pandemic could have a material

adverse impact on the Company’s business and financial results, including the timing and ability of the Company to raise capital,

initiate and/or complete current and/or future preclinical studies and/or clinical trials;

disrupt the Company’s regulatory activities;

and/or have other adverse effects on the Company’s clinical development.

STAFF COMMENTS.

currently lease approximately 4,500 square feet of space for operations in Century Park, Knoxville, TN.

Our monthly rental charge

for these offices is approximately $7,944 per month.

Our monthly rental charge for

these offices is approximately $6,100 per month.

The lease is for five years and expires on June 30, 2022.

information required by this item is incorporated by reference from Part II, Item 8.

Financial Statements and Supplementary Data,

Notes to Consolidated Financial Statements, Note 13 –

Financial Statements and Supplementary Data, Notes

to Consolidated Financial Statements, Note 15 – Commitments, contingencies and litigation.

SAFETY DISCLOSURES.

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

What changed 10-K

Item 1A. Risk Factors