GLSI US Equity☆

UNITED

STATES

SECURITIES

AND EXCHANGE COMMISSION

Washington,

D.C. 20549

Form

10-K

(Mark

One)

For

the fiscal year ended December 31, 2021

For

the Transition Period from to

Commission

File Number: 001-39555

GREENWICH

LIFESCIENCES, INC.

(Exact

name of registrant as specified in its charter)

(Address of principal executive offices) (Zip Code)

(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Act:

Title of each class Name of each exchange on which registered

Common Stock, $0.001 par value The NASDAQ Capital Market

Securities registered pursuant to Section 12(g) of the Act: None

Indicate

by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No

☒

Indicate

by check if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No

☒

Indicate

by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange

Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)

has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate

by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive

Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the

preceding 12 months (or for such shorter period that the registrant was required to submit and post such files). Yes ☒ No

☐

Indicate

by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K (§229.405 of this chapter) is not contained

herein, and will not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated

by reference in Part III of this Form 10-K or any amendment to this Form 10-K. ☒

Indicate

by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or a smaller reporting

company. See the definitions of “large accelerated filer”, “accelerated filer”, “smaller reporting company”,

and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If

an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying

with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate

by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness

of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered

public accounting firm that prepared or issued its audit report. ☐

Indicate

by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒

The

aggregate market valueof

the voting and non-voting common equity held by non-affiliates based on a closing sale price of $44.94 per share, which was the last

sale price of the common stock as of June 30, 2021, the last business day of the registrant’s most recently completed second fiscal

quarter, was $171,492,883.

As

of March 21, 2022, 12,951,453

shares of the registrant’s common stock, $0.001 par value per share, were issued and outstanding.

TABLE

OF CONTENTS

Page

PART I

Item 1 Business 6

Item 1A Risk Factors 22

Item 1B Unresolved Staff Comments 50

Item 2 Properties 50

Item 3 Legal Proceedings 50

Item 4 Mine Safety Disclosures 50

PART II

Item 6 [Reserved] 51

Item 7A Quantitative and Qualitative Disclosures About Market Risk 54

Item 8 Financial Statements and Supplementary Data 54

Item 9A Controls and Procedures 54

Item 9B Other Information 54

Item 9C Disclosure Regarding Foreign Jurisdictions that Prevent Inspections. 54

PART III

Item 10 Directors, Executive Officers, and Corporate Governance 55

Item 11 Executive Compensation 59

Item 14 Principal Accountant Fees and Services 62

PART IV

SIGNATURES 64

Table of Contents

Forward-Looking

Statements

This

Annual Report on Form 10-K contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of

the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as

amended (the “Exchange Act”). These statements may be identified by such forward-looking terminology as “may,”

“should,” “expects,” “intends,” “plans,” “anticipates,” “believes,”

“estimates,” “predicts,” “potential,” “continue” or the negative of these terms or other

comparable terminology. Our forward-looking statements are based on a series of expectations, assumptions, estimates and projections

about our company, are not guarantees of future results or performance and involve substantial risks and uncertainty. We may not actually

achieve the plans, intentions or expectations disclosed in these forward-looking statements. Actual results or events could differ materially

from the plans, intentions and expectations disclosed in these forward-looking statements. Our business and our forward-looking statements

involve substantial known and unknown risks and uncertainties, including the risks and uncertainties inherent in our statements regarding:

● our projected financial position and estimated cash burn rate;

● our estimates regarding expenses, future revenues and capital requirements;

● our ability to continue as a going concern;

● our need to raise substantial additional capital to fund our operations;

● the success, cost and timing of our clinical trials;

● our dependence on third parties in the conduct of our clinical trial;

● the results of market research conducted by us or others;

● our reliance on third-party suppliers and manufacturers;

● the success of competing therapies and products that are or become available;

All

of our forward-looking statements are as of the date of this Annual Report on Form 10-K only. In each case, actual results may differ

materially from such forward-looking information. We can give no assurance that such expectations or forward-looking statements will

prove to be correct. An occurrence of, or any material adverse change in, one or more of the risk factors or risks and uncertainties

referred to in this Annual Report on Form 10-K or included in our other public disclosures or our other periodic reports or other documents

or filings filed with or furnished to the U.S. Securities and Exchange Commission (the “SEC”) could materially and adversely

affect our business, prospects, financial condition and results of operations. Except as required by law, we do not undertake or plan

to update or revise any such forward-looking statements to reflect actual results, changes in plans, assumptions, estimates or projections

or other circumstances affecting such forward-looking statements occurring after the date of this Annual Report on Form 10-K, even if

such results, changes or circumstances make it clear that any forward-looking information will not be realized. Any public statements

or disclosures by us following this Annual Report on Form 10-K that modify or impact any of the forward-looking statements contained

in this Annual Report on Form 10-K will be deemed to modify or supersede such statements in this Annual Report on Form 10-K.

This

Annual Report on Form 10-K may include market data and certain industry data and forecasts, which we may obtain from internal company

surveys, market research, consultant surveys, publicly available information, reports of governmental agencies and industry publications,

articles and surveys. Industry surveys, publications, consultant surveys and forecasts generally state that the information contained

therein has been obtained from sources believed to be reliable, but the accuracy and completeness of such information is not guaranteed.

While we believe that such studies, clinical trials and publications are reliable, we have not independently verified market and

industry data from third-party sources.

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Risk

Factor Summary

Our

business is subject to significant risks and uncertainties that make an investment in us speculative and risky. Below we summarize what

we believe are the principal risk factors but these risks are not the only ones we face, and you should carefully review and consider

the full discussion of our risk factors in the section titled “Risk Factors”, together with the other information in this

Annual Report on Form 10-K. If any of the following risks actually occurs (or if any of those listed elsewhere in this Annual Report

on Form 10-K occur), our business, reputation, financial condition, results of operations, revenue, and future prospects could be seriously

harmed. Additional risks and uncertainties that we are unaware of, or that we currently believe are not material, may also become important

factors that adversely affect our business.

Risks

Relating to Our Business

We

have incurred substantial losses since our inception and anticipate that we will continue to incur substantial and increasing losses

for the foreseeable future.

We

need significant additional financing to fund our operations and complete the development and, if approved, the commercialization of

our product candidate. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product development

programs or commercialization efforts.

Clinical-stage

biopharmaceutical companies with product candidates in clinical development face a wide range of challenging activities which may entail

substantial risk.

We

may find it difficult to enroll patients in our clinical trials given the limited number of patients who have the diseases for which

our product candidate is being studied which could delay or prevent the start of clinical trials for our product candidate.

The

results of preclinical studies or earlier clinical trials are not necessarily predictive of future results. Our existing product candidate

in clinical trials, and any other product candidates that may advance into clinical trials, may not have favorable results in later clinical

trials or receive regulatory approval.

Clinical

drug development involves a lengthy and expensive process with an uncertain outcome.

Our

current and future product candidates, the methods used to deliver them or their dosage levels may cause undesirable side effects or

have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label or result

in significant negative consequences following any regulatory approval.

Our

product development program may not uncover all possible adverse events that patients who take our product candidate may experience.

The number of patients exposed to our product candidate and the average exposure time in the clinical development program may

be inadequate to detect rare adverse events or chance findings that may only be detected once the product is administered to more patients

and for greater periods of time.

Our

future success is dependent on the regulatory approval of our product candidate.

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We

have limited to no manufacturing, sales, marketing or distribution capability and must rely upon third parties for such.

We

are subject to a multitude of manufacturing risks, any of which could substantially increase our costs and limit supply of our product

candidate.

In

the clinical trials using GP2, GM-CSF is also administered and its availability is dependent upon a third-party manufacturer, which may

or may not reliably provide GM-CSF, thus jeopardizing the completion of the trials.

We

rely on third parties to conduct our preclinical studies and clinical trials. If these third parties do not successfully carry out their

contractual duties or meet expected deadlines, or if we lose any of our CROs or other key third-party vendors, we may not be able to

obtain regulatory approval for or commercialize our current or future product candidates on a timely basis, if at all.

We

are dependent on technologies we license, and if we lose the right to license such technologies or we fail to license new technologies

in the future, our ability to develop new products would be harmed, and if we fail to meet our obligations under our license agreements,

we may lose the ability to develop our product candidate.

Our

commercial success depends upon attaining significant market acceptance of our current product candidate and future product candidates,

if approved, among physicians, patients, healthcare payors and cancer treatment centers.

Even

if we are able to commercialize our current product candidate or any future product candidates, the products may not receive coverage

and adequate reimbursement from third-party payors in the U.S. and in other countries in which we seek to commercialize our products,

which could harm our business.

We

face substantial competition, which may result in others discovering, developing or commercializing products before or more successfully

than we do.

The

price of our common stock may fluctuate substantially.

Because

certain of our stockholders control a significant number of shares of our common stock, they may have effective control over actions

requiring stockholder approval.

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PART

I

ITEM

1. BUSINESS

BUSINESS

Overview

We

are a clinical-stage biopharmaceutical company focused on the development of GP2, an immunotherapy to prevent breast cancer

recurrences in patients who have previously undergone surgery. GP2 is a 9 amino acid transmembrane peptide of the HER2/neu

protein, a cell surface receptor protein that is expressed in a variety of common cancers, including expression in 75% of breast

cancers at low (1+), intermediate (2+), and high (3+ or over-expressor) levels. The combination of GP2 + GM-CSF is called GLSI-100.

In a completed randomized, single-blinded, placebo-controlled, multi-center Phase IIb clinical trial led by MD Anderson Cancer

Center, no recurrences were observed in patients treated with GLSI-100 in the HER2/neu 3+ adjuvant setting after

median 5 years of follow-up, if the patients were treated, followed, and remained disease free over the first 6 months, which

is the time required to reach peak immunity and thus maximum efficacy and protection (p = 0.0338). For the 146 patients who have been

treated with GLSI-100 to date over 4 clinical trials, treatment was well tolerated and no serious adverse events were observed related

to the immunotherapy. We are planning to commence Flamingo-01, a Phase III clinical trial with Baylor College of Medicine

as the global primary investigator site. Flamingo-01 is designed to evaluate the safety and efficacy of GLSI-100 in HER2/neu positive

patients with residual disease or high-risk pathologic complete response at surgery and who have completed both neoadjuvant and postoperative

adjuvant trastuzumab based treatment. The Phase III clinical trial protocol including the patient population, trial size, statistical

analysis plan, interim analysis, adaptive features, and manufacturing information are still under discussion with the FDA and therefore

subject to change. We are also currently completing the last steps to manufacture GP2 clinical drug product and to

open clinical sites.

Our

Product Candidate

GP2

is a HER2/neu transmembrane peptide that elicits a targeted immune response against HER2/neu-expressing cancers. Below

is an image of a cell surface showing therapeutically relevant cell surface proteins in cancer. Breast cancers and other solid tumors

with elevated expression of HER2/neu protein are highly aggressive with an increased disease recurrence and a worse prognosis.

GM-CSF

Immunoadjuvant

Recombinant

human granulocyte macrophage colony-stimulating factor or GM-CSF (sargramostim, Leukine®) has been shown to enhance monocyte and

neutrophil cytotoxicity against melanoma tumor cells and to enhance activity-dependent cellular cytotoxicity of monocytes and

neutrophils against targets coated with the anti-ganglioside antibodies. GP2 will be delivered in combination with GM-CSF to induce GP2

peptide specific immunity. GP2 treatment is administered via an intradermal injection by mixing GP2 peptide and GM-CSF at the time of

administration.

GM-CSF is available in lyophilized form exclusively

from one manufacturer. We will continue to be dependent on the manufacturer for our supply of GM-CSF in our ongoing GP2

clinical trials and upon potential commercialization of GP2. Although GM-CSF is only approved for sale in the U.S. by the

FDA and is available in other countries on a named patient basis through a specialized company that focuses on making products

approved in the U.S. available globally, GM-CSF may be registered for sale in other countries by the manufacturer in the future.

Cancer

Immunotherapy

Cancer

immunotherapy is a new method of cancer treatment among more established treatment options such as surgery, chemotherapy, targeted therapy,

and radiation therapy. This method seeks to stimulate an individual’s immune system to selectively attack cancer cells while not

affecting normal cells or to deliver certain immune system components in order to inhibit the spread of cancer. Thus,

cancer immunotherapy is an important and rapidly emerging field, which has led to new clinical research studies and garnered the attention

of biotechnology and pharmaceutical companies, regulatory agencies, payors and hospital systems, cancer patients and their families,

and the general public at large.

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Cancer

immunotherapy harnesses the body’s natural immune system response to fight and/or prevent tumor growth. An essential characteristic

of the immune system, which is a network of tissues, cells, and signaling molecules that work to protect the body, is its ability to

differentiate foreign threats, including cancerous growths, from normal cells. Despite the fact that tumor cells originate from normal

cells, tumor cells can be recognized as foreign threats because of their ability to elicit the production of tumor antigens. These antigens

may be released in the interstitial tissues, and eventually in the bloodstream or may remain on the surface of cognate cancer cells.

The HER2/neu protein is one of the most widely expressed tumor antigens in multiple malignances.

Several

cell types play an important role in the development and maintenance of immune responses against cancer. The most important cell types

with regard to immune response are antigen-presenting cells (“APCs”) and lymphocytes. APCs include various subtypes, such

as dendritic cells, monocytes and macrophages. Once a patient is exposed to a tumor antigen (either by the presence of cancer itself

or through active immunization through a vaccine type immunotherapeutic), the tumor antigen gets recognized by the APC and becomes “processed”

through digestion into smaller fragments within the APC. Subsequently, the APC “communicates” with a specific type of lymphocyte

called a T-cell. Inactive T-cells search for tumor antigens by transiently binding to antigens presented by major histocompatibility

complexes (“MHCs”) on the APCs. There is great variability in the expression of different subtypes of MHCs in the human population.

The MHC system expresses human leukocyte antigens (“HLAs”) and these HLA subtypes determine the vigor and duration of any

given T-cell response to a cancer among different patients.

As

shown below, following GP2 immunotherapy, CD8+ cytotoxic T lymphocytes recognize and destroy HER2/neu-expressing cancer cells.

GP2 is administered in combination with an FDA-approved immunoadjuvant GM-CSF, which stimulates the proliferation of antigen presenting

cells. Preclinical studies have shown that T cells sensitized against the GP2 peptide demonstrate significant recognition of HER2/neu-expressing

tumors. Both ovarian and breast cancer-specific CTLs recognize GP2, which is widely expressed in HER2/neu-expressing tumors and

is capable of inducing tumor-specific CTL populations in vitro.

Breast

Cancer Treatment Approach — Adjuvant & Neoadjuvant Treatments

As

shown below, in the adjuvant setting, a HER2/neu 3+ patient typically receives Herceptin in the first year following breast cancer

surgery, with the hope that their breast cancer will not recur, and with the odds of recurrence slowly decreasing over the first 5 years

following surgery. Herceptin has been shown to reduce recurrence rates by approximately 50%, from 25% to 12%, in the adjuvant setting.

In the neoadjuvant setting, a HER2/neu 3+ patient receives treatment before surgery and based on the results of a biopsy at surgery,

will receive Herceptin or Kadcyla, a more potent form of Herceptin, following surgery. Kadcyla has been shown to reduce recurrence rates

by 50%, from 22% to 11%, in the neoadjuvant setting. Accordingly, we believe that GP2 may be effective in safely addressing the 50% of

recurring patients who do not respond to either Herceptin or Kadcyla.

GP2

is administered in combination with the immunoadjuvant GM-CSF in years 2-4, following the first year of treatment with Herceptin, in

a series of 11 intradermal injections comprising 6 primary injections over 6 months (1 injection per month) followed by 5 booster injections

every 6 months thereafter.

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The adverse events observed to date have been

well-tolerated with no SAEs reported in the Phase IIb clinical trial considered related to GLSI-100 treatment. Therefore, we believe

that GLSI-100 is well-positioned to serve this population at this stage of treatment. We believe that clinicians and patients are

seeking a de-escalation and a return to normal life free of toxic treatments, especially if the chance of recurrence is reduced

substantially. Based on the results of our clinical studies to date, we believe that GLSI-100 may significantly reduce the incidence

of recurrence/metastatic disease and need for additional therapy. Lastly, we believe that GP2 may be the treatment that will

synergistically overlap with or follow trastuzumab based treatments, such as Herceptin, Kadcyla, Enhertu or any of the other

Herceptin derivatives or antibody drug conjugates being developed.

GP2

Clinical Data & Planned Phase III Trial

In

the Phase IIb and 3 Phase I clinical trials where 146 patients received GP2 immunotherapy, there were no serious adverse events

observed related to the immunotherapy or any other GP2 combination treatments.

Clinical Trial Description Status

GP2 Phase III Clinical Trial – Flamingo-01 Planned

GP2 Phase IIb Clinical Trial Trial Completed

● 89 patients treated with GP2 + GM-CSF, 91 placebo patients treated with GM-CSF

GP2 Phase I Clinical Trial — Combination with AE37 Trial Completed

● 22 patients treated with GP2 + AE37 + GM-CSF

GP2 Phase I Clinical Trial — Combination with Trastuzumab Trial Completed

● 17 patients treated with GP2 + GM-CSF + trastuzumab

First GP2 Phase I Clinical Trial Trial Completed

● Phase Ib Trial of HER2/neu Peptide (GP2) Vaccine in Breast Cancer Patients

● 18 patients treated with GP2 + GM-CSF

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Phase

I Clinical Trials

First

GP2 Phase I Clinical Trial

As

shown in the table above, the first GP2 Phase I clinical trial was conducted at Walter Reed Army Medical Center. The clinical

trial was conducted in patients over the age of 18 years with a diagnosis of HER2/neu 1-3+, node negative breast cancer who had

undergone primary surgical and medical therapies and who were without evidence of disease at the time of enrollment into the clinical

trial. Patients were HLA typed and HLA-A*02 patients were skin tested for recall antigens. HLA-A*02 patients found

to be immunologically intact received the vaccine. There were no grade 3-5 toxicities observed among the 18 patients that received

a total of 108 doses of GP2 + GM-CSF. Among all patients who participated in the clinical trial, the maximum observed

local toxicity that occurred was grade 1 in 38.9% and grade 2 in 61.1% of the patients. The maximum systemic toxicity observed

during the clinical trial was grade 0 in 5.6%, grade 1 in 61.1%, and grade 2 in 33.3% of the patients. The most common local

reactions included erythema and induration (100% of patients), pruritis (25%), and inflammation (23%). The most common systemic reactions

were grade 1 fatigue (40%) and grade 1 arthralgia/myalgia (15%). There were no recurrences and no deaths reported among the patients

who participated in the clinical trial. Additional data analysis reported by the investigators included topics such as pre-existing

immunity, effects of dosing, and epitope spreading.

GP2

Phase I Clinical Trial — Combination with Trastuzumab

Preclinical

research previously demonstrated that a synergy may exist between trastuzumab and GP2 peptide-stimulated CTLs ex vivo. Pretreatment

of breast cancer cells with trastuzumab followed by incubation with GP2 peptide-induced CTLs resulted in enhanced cytotoxicity in 3 tumor

cell lines compared to treatment with trastuzumab or GP2-specific CTLs alone. These results suggest that concurrent GP2 vaccination during

trastuzumab therapy may be a possible combination immunotherapy.

As

shown in the table above, a Phase I trial evaluating the combination therapy of GP2 + GM-CSF administered simultaneously with trastuzumab

was conducted. The combination therapy was found to be well tolerated when given concurrently in 17 clinically disease-free, HER2/neu

over-expressing breast cancer patients.

GP2

Phase I Clinical Trial — Combination with AE37

As

shown in the table above, a Phase I trial evaluating the combination therapy of GP2 + GM-CSF administered simultaneously with

HER2/neu peptide AE37 in 22 clinically disease-free, HER2/neu breast cancer and ovarian cancer patients was

conducted. While 28 patients enrolled, 22 were treated and 14 patients completed the 6 vaccination series. Final results

of this Phase I trial suggest that the combination of GP2 and AE37 peptides is well tolerated at each of the

tested dosing levels. Additionally, we believe that the combination is capable of stimulating strong peptide-specific in vivo

immune responses.

During

the primary vaccination series, an AE37/GP2+GM-CSF dual peptide vaccine resulted in robust T-cell proliferation. However, significant

immune responses became more variable at 6 and 12 months post vaccination suggesting the need for boosters in some individuals.

Phase

II Clinical Trial

GP2

Phase IIb Clinical Trial Overview

In

a prospective, randomized, single-blinded, placebo-controlled, multi-center (16 sites led by MD Anderson Cancer Center) Phase

IIb clinical trial of HLA-A*02 breast cancer patients, GLSI-100 treatment resulted in no recurrences in 46 HER2/neu

3+ over-expressor patients versus 50 placebo patients who were treated with GM-CSF. After 5 years of follow-up, there were 0%

cancer recurrences in the HER2/neu 3+ patients treated with GLSI-100 versus an 11% cancer recurrence rate in the

placebo arm treated with GM-CSF (p = 0.0338) in the population that was treated, followed, and remained disease free over the first

6 months, which we believe is the time required to reach peak immunity and thus maximum efficacy and protection. Based on this data,

we believe that treatment with GLSI-100 starting approximately in the second year following surgery may dramatically lower breast

cancer recurrences in this patient population.

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The

design of the Phase IIb trial was as follows:

The Phase IIb clinical trial closed in

December 2018. The final median 5 year follow-up data is presented below. A total of 180 intent-to-treat patients enrolled in the

clinical trial. HER2/neu status was determined based on the expression levels of the HER2/neu protein in each patient

using standard of care HER2/neu diagnostic technology. The trial was prospectively designed to analyze these fully treated

patients by 2 distinct patient populations, namely HER2/neu 3+ (positive or over expressors) and HER2/neu 1-2+ (low to

intermediate expressors):

5 Year Data Set of GP2 Phase IIb Trial: HER2 3+ (Positive or Over Expressors)

Patients Who are in the Efficacy Population

The

figure below shows a time series of the GLSI-100 immunotherapy injections, adverse events (“AE”), immune response, and

100% disease-free survival (0% recurrence rate) in HER2 positive breast cancer patients over median 5 years. This time series

highlights the effect of the 10 GLSI-100 immunotherapy injections over the first 2.5 years (as depicted by the 10 arrows on the

x-axis). We observed a potent immune response which typically peaked at 6 months. The immune response also included injection site

and systemic reactions that typically peaked at approximately 6 months. We believe that these AEs are a positive sign that the

immune system responded to GLSI-100 immunotherapy and contributed to the decline in metastatic breast cancer recurrence. The

observed AEs associated with GLSI-100 injections were temporary and declined after GLSI-100 injections ended.

Safety

& Immune Response Data of GP2 Phase II Trial

In both the HER2/neu 3+ and the HER2/neu

1-2+ patient populations, GP2 was shown to be well tolerated. The observed AEs primarily consisted of injection site reactions

which could be mitigated by reducing the GM-CSF dose (and then the GP2 dose, if necessary). No SAEs reported in the GP2 treated

patients were considered attributable to GLSI-100.

GLSI-100

immunotherapy demonstrated GP2-specific immune responses. We believe that this data and the absence of observed metastatic breast cancer

recurrence in the HER2/neu 3+ population in the Phase IIb clinical trial support GP2’s mechanism of action. Statistically

significant peak immunity was typically observed after 6 months of GLSI-100 treatment, as measured in both the Dimer Binding Assay and

the Delayed Type Hypersensitivity (DTH) skin test. The HER2/neu 3+ population’s immune response was similar to the HER2/neu

1-2+ population’s immune response, suggesting the potential to treat the HER2/neu 1-2+ population (including triple

negative breast cancer) with GP2 immunotherapy in combination with trastuzumab (Herceptin) based products and other synergistic clinically

active agents. The broad based immune response suggests the potential for GP2 to treat other HER2/neu 1-3+ expressing cancers.

Further, booster injections given every 6 months after the PIS were observed to elicit a prolonged immune response,

which may provide longer term protection.

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Planned

Phase III Trial, Flamingo-01

We

are planning to commence a Phase III clinical trial with an interim analysis and are currently completing the last steps to manufacture

GP2 clinical drug product and to open clinical trial sites, using a similar treatment regime as the Phase IIb clinical

trial. The Phase III clinical trial protocol including the patient population, trial size, statistical analysis plan, interim analysis,

adaptive features, and manufacturing information are still under discussion with the FDA and therefore subject to change.

The

primary objective of Flamingo-01 is to assess the safety and efficacy of GLSI-100 compared to placebo in HLA-A*02 positive and HER2/neu

positive breast cancer patients who have a high risk of disease recurrence (stage I, II, or III at presentation with residual disease

at surgery or stage III at presentation with pathologic complete response (“pCR”) at surgery) and have completed both neoadjuvant

and postoperative adjuvant trastuzumab-based standard of care therapy.

An

overview of the anticipated Phase III clinical trial design is shown below:

U.S. Breast Cancer Market

We

believe that the market for GP2 is large. The American Cancer Society estimates that approximately 1 in 8 U.S. women (12.8%)

will develop invasive breast cancer over her lifetime, with approximately 282,000 new breast cancer patients per year and 3.8 million

current breast cancer survivors in the U.S. in 2021. An estimated 43,600 female breast cancer deaths will occur in the U.S. in 2021.

HER2/neu 3+ breast cancer patients comprise approximately 25% of all breast cancer patients. Approximately 40% to 50% of the

U.S. population contains the HLA-A*02 allele, while node positive and high risk node negative patients comprise approximately

50% of the market. Therefore, we believe that the U.S. market for the first indication for GP2, if approved, could be the combination of the

three populations above which together comprises approximately 6% of breast cancer patients who undergo surgery.

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Competition

Cancer

immunotherapy has become a significant growth area for the biopharmaceutical industry, attracting large pharmaceutical companies as well

as small niche players. Generally, our principal competitors in the cancer immunotherapy market comprise both types of companies with

currently approved products for various indications, such as manufacturers of approved bispecific antibodies, CAR-T cells, and checkpoint

inhibitors, as well as companies currently engaged in cancer immunotherapy clinical development. The large and medium-size players who

have successfully obtained approval for cancer immunotherapy products include Bristol-Myers Squib Company, Merck & Co., Inc., Genentech,

Inc. (a subsidiary of Roche Holding AG), AstraZeneca PLC, Celgene Corporation, Johnson & Johnson, Amgen, Novartis, Juno Therapeutics,

Inc. (a subsidiary of Celgene), Kite Pharma, Inc., a wholly-owned subsidiary of Gilead Sciences, Inc. and Pfizer, Inc./EMD Serono, Inc.

Most of these companies, either alone or together with their collaborative partners, have substantially greater financial resources than

we do.

Companies

developing novel products with similar indications to those we are pursuing are expected to influence our ability to penetrate and maintain

market share, if GLSI-100 is approved. For patients with early stage breast cancer, adjuvant or neoadjuvant therapy is

often given to prevent recurrence and increase the chance of long-term disease free survival. Adjuvant or neoadjuvant therapy

for breast cancer can include chemotherapy, hormonal therapy, radiation therapy, or combinations thereof. In addition, the HER2 targeted

drug Herceptin (trastuzumab or biosimilar) alone or in combination with Perjeta (pertuzumab), both manufactured and marketed by

Roche/Genentech, may currently only be given to patients with tumors with high expression of HER2/neu. Following adjuvant

treatment in the first year following surgery, only Nerlynx is approved for extended andjuvant treatment and would potentially compete

with GLSI-100 if not used synergistically.

There

are a number of approved HER2/neu targeted therapies, some of which include the following: Genentech’s Herceptin, Perjeta

(pertuzumab) and Kadcyla (TDM-1, ado-trastuzumab emtansine); Puma’s Nerlynx (neratinib); Daichi Sanko’s Enhertu

(DS-8201, fam-trastuzumab deruxtecan-nxki), and Seattle Genetics’ Tukysa (tucatanib). In addition, the following biosimilars

to trastuzumab have been approved: Biocon/Mylan’s (Ogivri — trastuzumab-dkst; Celltrion/Teva’s (Herzuma — trastuzumab-pkrb);

Samsung/Biogen/Merck’s (Ontruzant — trastuzumab-dttb); Pfizer’s (Trazimera — trastuzumab-qyyp); and Allergan/Amgen’s

(Kanjinti; trastuzumab-anns). Furthermore, the following immune checkpoint inhibitors have also been approved or are under review by

the FDA to treat breast cancer patients: Merck’s Keytruda (pembrolizumab) and Genentech’s Tecentriq (atezolumab). Moreover

we believe that drug candidates from Sellas (formerly Galena), Marker (formerly TapImmune), Epithany, Antigen Express (Generex subsidiary),

and various companies pursuing neoantigen technologies are in clinical development and are being pursued for different sub-populations

or are behind GP2 in clinic development.

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Many

of our competitors, either alone or with their strategic partners, have substantially greater financial, technical and human resources

than we do, and more experience in obtaining FDA and other regulatory approvals of treatments and in commercializing those treatments.

Accordingly, our competitors may be more successful than us in obtaining approval for cancer immunotherapy products and achieving widespread

market acceptance. Our competitors’ treatments may be more effectively marketed and sold than any products we may commercialize,

thus causing limited market share before we can recover the expenses of developing and commercializing our cancer immunotherapy product

candidate.

Mergers

and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated among a smaller

number of our competitors. Smaller or early stage companies may also prove to be significant competitors, particularly through collaborative

arrangements with large and established companies. These activities may lead to consolidated efforts that allow for more rapid development

of cancer immunotherapy product candidates.

These

competitors also compete with us in the recruiting and retaining of qualified scientific and management personnel, the ability to work

with specific clinical contract organizations due to conflict of interest, and the conduct of trials in the ability to recruit clinical

trial sites and patients for our clinical trials.

We

expect any products that we develop and commercialize to compete on the basis of, among other things, efficacy, safety, price, and the

availability of coverage and reimbursement from government and other third-party payors. Our commercial opportunity could be reduced

or eliminated if our competitors develop and commercialize products that are viewed as safer, more convenient, or less expensive than

any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than

we may obtain approval for our current product candidate or any other future product candidate, which could result in our competitors

establishing a strong market position before we are able to enter the market.

Manufacturing

We

do not own or operate manufacturing facilities for the production of our product candidate nor do we have plans to develop our own manufacturing

operations in the foreseeable future. We currently depend on third-party contract manufacturers for all of our required raw materials,

active pharmaceutical ingredients (“APIs”), and finished product candidate for our clinical trials and potential commercial

supply.

Exclusive

License

The

Henry M. Jackson Foundation out-licenses technology of the U.S. military and it conducts research and manages clinical trials.

HJF managed the GP2 Phase IIb clinical which was led by MD Anderson Cancer Center, oversaw all regulatory filings with the FDA for all

4 GP2 clinical trials (including the 3 Phase I and the Phase IIb clinical trials), and possesses all patient and manufacturing

data from such trials.

In

April 2009, we entered into an exclusive license agreement, as amended, with HJF pursuant to which HJF granted us exclusive worldwide

rights to several U.S. and foreign patents and patent applications covering methods of using GP2 as an immunotherapy that elicits a targeted

immune response against HER2/neu-expressing cancers. In consideration for such licensed rights, we issued HJF 202,619 shares of

our common stock. In addition, we are required to pay an annual maintenance fee and milestone payments of up to an aggregate of $5.7

million. We are also required to make 2.5-5% royalty payments based on the sales of GP2 and to reimburse HJF for patent expenses. To

date we have not been required to make any milestone or royalty payments to HJF. The term of the exclusive license shall terminate at

such time that the last licensed patent or patent application expires or is abandoned, unless terminated earlier pursuant to the terms

of the exclusive license agreement. We may terminate the license by giving 90 days notice. HJF may terminate the license if we do not

make required payments, if we default in our performance obligations, if we do not sufficiently develop and advance GP2 towards commercialization,

and for various other reasons.

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In

connection with the exclusive license agreement with HJF, we were the financial and corporate sponsors of the GP2 Phase IIb clinical

trial. HJF has provided us with all FDA correspondences and GP2 patient and manufacturing data for the history of the drug’s development

for all 4 clinical trials, and we have incorporated this data into our corporate investigational new drug application (“IND”)

with the FDA.

Intellectual

Property Portfolio

Our

commercial success depends in part on our ability to avoid infringing the proprietary rights of third parties, our ability to obtain

and maintain proprietary protection for our technologies where applicable, and our ability to prevent others from infringing our proprietary

rights. We intend to protect our proprietary technologies by, among other methods, evaluating relevant patents, establishing defensive

positions, monitoring European Union oppositions and pending intellectual property rights, preparing litigation strategies in view of

the U.S. legislative framework, and filing U.S. and international patent applications on technologies, inventions and improvements that

are important to our business. Patents and other intellectual property rights are crucial to our success. We intend to protect our intellectual

property rights through available means including filing and prosecuting patent applications in the U.S. and other countries, protecting

trade secrets, and utilizing regulatory protections such as data exclusivity. In addition, we include restrictions regarding use and

disclosure of our proprietary information in our contracts with third parties, and utilize customary confidentiality agreements with

our employees, consultants, clinical investigators, and scientific advisors to protect our confidential information and know-how. Together

with our licensors, we also rely on trade secrets to protect our combined technology especially where we do not believe patent protection

is appropriate or obtainable. It is our policy to operate without knowingly infringing on, or misappropriating, the proprietary rights

of others.

An

international patent law treaty (“PCT”) provides a unified procedure for filing patent applications to protect inventions

in each of its contracting states. Thus, a single PCT application can be converted into a national stage patent application in any of

the more than 145 PCT contracting states, and is considered a simple, cost-effective means for seeking patent protection in numerous

regions or countries. This nationalization (converting into an application in any of the contracting states) typically occurs 18 months

after the PCT application filing date. We also rely on trade secrets, know-how, and continuing technological innovation to develop and

maintain our proprietary position.

The

term of individual patents depends upon the legal term of the patents in countries in which they are obtained. In most countries, including

the U.S., the patent term is generally 20 years from the earliest date of filing a non-provisional patent application in the applicable

country. In the U.S., a patent’s term may, in certain cases, be lengthened by patent term adjustment, which compensates a patentee

for administrative delays by the U.S. Patent and Trademark Office in examining and granting a patent or may be shortened if a patent

is terminally disclaimed over a commonly owned patent or a patent naming a common inventor and having an earlier expiration date.

HJF

License

Pursuant

to our exclusive license agreement with HJF, we were granted exclusive worldwide rights to several U.S. and foreign patents and patent

applications covering methods of using GP2. The GP2 issued patents provide protection ranging from 2026 through 2032 in major markets

such as the U.S., Europe, Japan, Australia, and Canada, with ongoing prosecution of pending patent applications in other markets. We

plan to register GP2 as a biologic, which may be subject to 10-12 years market exclusivity in the U.S. upon receiving marketing approval.

The

following summarizes the two patent families subject to our exclusive license agreement with HJF. We have licensed rights to issued patents

and pending patent applications in certain countries with respect to the two patent families below and do not own or have rights to any

other patents or patent applications for GP2 or any other products:

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Corporate

Strategy

We

do not have a sales, marketing, or product distribution strategy for our GP2 immunotherapy or any future product candidates because GP2

is still in clinical development. Our future commercial strategy, if our GP2 immunotherapy or any future product candidates are approved,

may include the use of strategic partners, distributors, a contract sales force, or the establishment of our own commercial and specialty

sales force for the U.S. market, as well as similar strategies for regions and territories outside the U.S. We plan to further evaluate

these options as we approach submission of a new drug application or biologics license application for one of our

product candidates for one or more indications.

The

GP2 issued patents provide protection ranging from 2026 through 2032 in various markets, and we plan to register GP2 as a biologic, which

may be subject to 12 years market exclusivity in the U.S. upon receiving marketing approval. During this period of exclusivity, we

intend to advance GP2 into a Phase III clinical trial in the U.S. and pursue a European and global clinical trial strategy to support

GP2 registration outside of the U.S. We are considering various options to fund the Phase III clinical trial including financing and/or

strategic transactions. Our strategy during such time also includes building a commercialization team, pursuing additional funding, and

pursuing strategic collaborations to support the future global marketing and sales of GP2, if approved. A long term global and

regional licensing process has been initiated and will continue as the Phase III trial commences.

Pipeline

Strategy — Including GP2 In Other HER2/neu-Expressing Cancers

We are developing follow-on indications for GP2

by designing and planning additional clinical trials to expand the breast cancer patient population and to pursue additional HER2/neu-expressing

cancers. Pending the receipt of sufficient capital, we may conduct additional clinical trials designed to evaluate the safety

and efficacy of GLSI-100 in (1) patients immediately upon diagnosis in parallel to neoadjuvant treatment and surgery to provide maximum

protection against breast cancer recurrence as soon as possible, (2) other HLA patients in the same HER2/neu 3+ breast cancer

patient population, (3) breast cancer patients who are low to intermediate expressors of HER2/neu (1-2+) or (4) other HER2/neu-expressing

cancers including, but not limited to, ovarian, gastrointestinal, and colon cancers.

Government

Regulations

The

FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among

other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging,

storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting

of biologics such as those we are developing. Along with third-party contractors, we will be required to navigate the various preclinical,

clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct clinical

trials or seek approval or licensure of our current product candidate or any future product candidates. The process of obtaining regulatory

approvals and the subsequent compliance with appropriate federal, state, local, and foreign statutes and regulations require the expenditure

of substantial time and financial resources. A company can make only those claims relating to safety and efficacy, purity and potency

that are approved by the FDA and in accordance with the provisions of the approved label.

The