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Item 1. Business

2022-03-21 compared with 2021-03-31 · 731 added, 808 removed, 99 unchanged (94% of the section changed)

are a biopharmaceutical company that is developing GP2, an immunotherapy designed to prevent the recurrence of breast cancer following

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.

In a completed Phase IIb clinical trial led by MD Anderson Cancer Center, no recurrences were observed

in the HER2/ neu 3+ adjuvant setting after median 5 years of follow-up, if the patient received the 6 primary intradermal

injections over the first 6 months.

We are planning to commence a Phase III clinical trial in 2021.

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.

Product Candidate

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.

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.

Immunoadjuvant

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

as well as 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.

is available in both liquid and lyophilized forms exclusively from one manufacturer, and we will continue to be dependent on such

manufacturer for our supply of GM-CSF in combination with GP2 in our ongoing GP2 trials and upon potential commercialization of

Although GM-CSF is currently approved for sale in the U.S.

by the FDA and is available in other countries on a name 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 such manufacturer in the future.

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.

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.

Immunotherapy

immunotherapies seek to stimulate an individual’s own immune system to selectively attack cancer cells while not affecting

normal cells or delivering certain immune system components in order to inhibit the spread of cancer.

Cancer immunotherapy drugs

are a new method of cancer treatment which are in addition to more established treatment options such as surgery, chemotherapy,

targeted therapy, and radiation therapy.

Therefore, 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.

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

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.

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.

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

These antigens may be released in the interstitial tissues, and eventually in the bloodstream or may remain on the surface

of cognate cancer cells.

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.

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”

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.

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

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.

Cancer Treatment Approach —

Adjuvant & Neoadjuvant Treatments

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.

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.

Furthermore, we believe that recently approved drugs such as Perjeta and Nerlynx do not

fully address this unmet need, even in their most efficacious subpopulations, and that in the initial GP2 indication, approximately

17,000 new patients may be eligible for GP2 treatment per year, which could save approximately 1,500 to 2,000 lives per year.

only injection site reactions were observed (which speaks to the immunogenicity of GP2) and no SAEs were reported in the GP2 Phase

IIb clinical trial, GP2 may be positioned as the final treatment for patients post-surgery.

Furthermore, 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.

Lastly, we believe that GP2 may be the treatment that will synergistically overlap with or follow Herceptin,

Kadcyla, or Enhertu (fam-trastuzumab deruxtecan-nxki, DS-8201) or any of the other Herceptin derivatives or antibody drug conjugates

being developed.

believe that U.S.

academic centers will be moving higher risk, node positive patients into neoadjuvant treatment and will use

Kadcyla if residual disease is observed at the time of surgery;

however community centers and international markets may not move

as quickly or at all, due to the high dual therapy costs and the lack of approval or reimbursement of Kadcyla in markets outside

GP2 will be pursued in both the adjuvant and neoadjuvant settings in HER2/ neu 3+ patients in our

planned Phase III trial.

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.

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

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

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.

Cancer Treatment Approach — Adjuvant & Neoadjuvant Treatments

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.

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.

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.

Clinical Data & Planned Phase III Trial

the Phase IIb and three Phase I clinical trials where 138 patients received GP2 immunotherapy, there were no SAEs reported in

any of the trials, including for GP2 and GM-CSF combination treatments or any other GP2 combination treatments.

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.

Trial Description

GP2 Phase III Clinical Trial –

A Randomized, Multicenter, Placebo-controlled, Phase

3 Study to Evaluate the Efficacy and Safety of HER2/ neu Peptide GLSI-100 (GP2 + GM-CSF) in HER2/ neu Positive Subjects

with Residual Disease or High-Risk PCR after both Neoadjuvant and Postoperative Trastuzumab-based Therapy

Phase IIb Clinical Trial

Randomized, Single-Blinded, Multi-Center Phase II Trial of the HER2/ neu Peptide GP2 + GM-CSF Vaccine versus GM-CSF

Alone in HLA-A02+ Node-Positive and High-Risk Node-Negative Breast Cancer Patients to Prevent Recurrence

Randomized, Single-Blinded, Multi-Center Phase II Trial of the HER2/ neu Peptide GP2 + GM-CSF Vaccine versus GM-CSF Alone in

HLA-A*02+ Node-Positive and High-Risk Node-Negative Breast Cancer Patients to Prevent Recurrence

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

Phase I Clinical Trial —

Combination with AE37

Phase I Clinical Trial — Combination with AE37

I Safety Trial of the GP2 + GM-CSF Vaccine in Combination with the Helper Peptide AE37 + GM-CSF Vaccine

patients treated with GP2 + AE37 + GM-CSF

Phase I Clinical Trial —

Combination with Trastuzumab

Phase I Clinical Trial — Combination with Trastuzumab

Ib Trial of Combination Immunotherapy with HER2/ neu Peptide GP2 + GM-CSF Vaccine and Trastuzumab in Breast Cancer Patients

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

The study 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 study.

were HLA typed and HLA-A02 patients were skin tested for recall antigens.

HLA-A02 patients found to be immunologically intact

received the vaccine.

There were no grade 3-5 toxicities among the 18 patients receiving a total of 108 doses of GP2 + GM-CSF.

Among all patients, the maximum local toxicity occurring during the entire series was grade 1 in 38.9% and grade 2 in 61.1% of

the patients.

The maximum systemic toxicity during the series was grade 0 in 5.6%, grade 1 in 61.1%, and grade 2 in 33.3% of the

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

The most common systemic reactions were grade 1 fatigue (40%) and grade 1 arthralgia/myalgia (15%).

There were no recurrences

and no deaths reported in study subjects.

Additional data analysis included topics such as pre-existing immunity, dosing, and

epitope spreading.

Phase I Clinical Trial —

Combination with Trastuzumab

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

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.

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.

Phase I Clinical Trial —

Combination with AE37

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

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.

Phase I Clinical Trial — Combination with Trastuzumab

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

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.

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.

Phase I Clinical Trial — Combination with AE37

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 14 clinically disease-free, HER2/ neu breast cancer and ovarian cancer patients was conducted.

While 28 patients enrolled, 14 patients completed the 6 vaccination series.

Initial results suggest that combining GP2 and AE37

peptides is well tolerated at all tested dosing levels.

Additionally, we believe the combination is capable of stimulating strong

peptide-specific in vivo immune responses.

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

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.

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

4 unchanged sentences

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

IIb clinical trial of HLA-A02 breast cancer patients, the combination of GP2-GMCSF-Herceptin treatment resulted in no recurrences

in 46 HER2/ neu 3+ over-expressor patients who were fully treated with GP2 versus 50 placebo patients who were treated with

GMCSF-Herceptin and who recurred at a rate similar to historical recurrence rates for patients treated with Herceptin.

5 years of follow-up, there were 0% cancer recurrences in the HER2/ neu 3+ patients treated with GP2-GMCSF-Herceptin, if

the patient received the 6 primary intradermal injections over the first 6 months, versus an 11% cancer recurrence rate in the

placebo arm treated with GMCSF-Herceptin ( p = 0.0338 ).

Thus, sequentially combining Herceptin in year 1 and GP2-GMCSF in

years 2-4 may dramatically lower breast cancer recurrences in this patient population.

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.

design of the Phase IIb trial was as follows:

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primary endpoint was to determine if GP2 + GM-CSF reduces breast cancer recurrence rates versus GM-CSF alone.

is defined as either a pathologically confirmed recurrence or a new radiographic finding during standard of care follow-up.

Phase IIb clinical trial closed in December 2018.

The final median 5 year follow-up data from this Phase IIb clinical trial is

currently being collected and analyzed.

+ GM-CSF Treated

Patients Recurrence Rate

Survival Analysis

the total 180 intent-to-treat patients enrolled, 168 patients completed the 6 primary intradermal injection series over the first

A recurrence is defined

as either a pathologically confirmed recurrence or a new radiographic finding of recurrence during standard of care follow-up.

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

1 unchanged sentence

The trial was prospectively designed to analyze these fully treated

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

3+ Over Expressors:

In the 96 HER2/ neu 3+, HLA-A02 patients, no recurrences were observed if the patient received

the 6 primary intradermal injections over the first 6 months following the first year of Herceptin treatment.

target population for our planned Phase III trial.

1-2+ Low to Intermediate Expressors:

In the 72 HER2/ neu 1-2+, HLA-A02 patients, no reduction in recurrence rates

were observed, but Herceptin was not administered to these patients.

Thus, we may pursue a future trial with GP2 in combination

with Herceptin therapy.

Antonio Breast Cancer Symposium Poster Presentation of Median 5 Year Top-Line Data

median 5 year top-line data described below was presented at the San Antonio Breast Cancer Symposium in a poster on December 9,

2020, entitled “Five year median follow-up data from a prospective, randomized, placebo-controlled, single-blinded, multicenter,

phase IIb study evaluating the reduction of recurrences using HER2/neu peptide GP2 + GM-CSF vs.

GM-CSF alone after adjuvant trastuzumab

in HER2 positive women with operable breast cancer.”

final analysis of the GP2 prospective, randomized, placebo-controlled, single-blinded, multicenter Phase IIb trial investigating

GP2+GM-CSF administered in the adjuvant setting to node-positive and high-risk node-negative breast cancer patients with tumors

expressing any degree of HER2 (immuno-histochemistry [IHC] 1-3+) ( NCT00524277 ) is now complete with 5 year follow-up.

trial enrolled HLA-A02 patients randomized to receive GP2+GM-CSF versus GM-CSF alone.

The trial’s primary objective was

to determine if treatment with GP2, a HER2-derived peptide, reduces recurrence rates.

enrolled and consented subject was randomized and scheduled to receive a total of 6 GP2+GM-CSF (500 mcg GP2:125 mcg GM-CSF) or

placebo (125 mcg GM-CSF alone) intradermal injections every 3-4 weeks as part of the Primary Immunization Series (“PIS”)

for the first 6 months and 4 GP2+GM-CSF booster or placebo intradermal injections every 6 months thereafter.

Boosters were introduced

during the trial, thus some patients did not receive all 4 boosters.

168 patient (Intent to Treat, “ITT”:

n=180) basket trial across 16 clinical sites explored 96 HER2 3+ patients, who

received a standard course of trastuzumab after surgery and subsequently completed the full PIS or placebo, starting the PIS at

median 17.1 months after surgery, and 72 HER2 1-2+ patients, who did not receive trastuzumab after surgery and subsequently completed

the full PIS or placebo, starting the PIS at median 10.8 months after surgery.

Subject disease characteristics are described in

GP2 is synergistic with trastuzumab, and the HER2 1-2+ patients did not receive trastuzumab, it was prespecified to compare recurrence

rates ITT versus per protocol in these 2 distinct, independently reported populations, excluding those patients who did not complete

Figure 1 depicts evidence that disease free survival (“DFS”) is more likely in HER2 3+ GP2-treated subjects

(p = 0.0338).

Figure 2 provides DFS for the HER2 1-2+ group.

was shown to be well tolerated with no SAEs and elicited a potent immune response measured by local skin tests and immunological

assays, which suggest peak immunity is reached at 6 months upon completion of the PIS.

Clinicopathologic Characteristics by Treatment Group for HER2 3+ and HER2 1-2+ Subjects Who Completed the PIS (1)

Continuous variables difference between treatment groups assessed by t-test.

Categorical variables difference between treatment

group distribution assessed by chi-square test.

shown above, after 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 46 HER2 3+ patients treated with GP2+GM-CSF,

if the patient completed the PIS, was 100% versus 89.4% (95% CI:76.2, 95.5%) in the 50 placebo patients treated with GM-CSF ( p

As shown in Table 1, the treated versus placebo HER2 3+ patients were well-matched, where approximately 53% were

stage T1, 41% were stages T2-T4, 55% were node positive, 58% were hormone receptor positive and received endocrine therapy, 77%

received adjuvant radiation, 77% received adjuvant chemotherapy, and 89% received trastuzumab.

shown above, after 5 years of follow-up, the Kaplan-Meier estimated 5-year DFS rate in the 35 HER2 1-2+ patients treated with

GP2+GM-CSF, if the patient completed the PIS, was 77.1% (95% CI:59.5, 87.9%) versus 77.6% (95% CI:60.1, 88.2%) in the 37 placebo

patients treated with GM-CSF ( p = 0.9142 ).

& Immune Response Data of GP2 Phase II Trial –

Median 3 Year Data

median 3 year interim analysis of the GP2 Phase II trial was published in 2016 and presented efficacy, safety, and immunological

data, and a median 4 year interim analysis of the GP2 Phase II trial was published in April 2020.

The safety and immunological

data is shown below.

both patient populations, GP2 was shown to be well tolerated, consisting of primarily injection site reactions which are caused

by GM-CSF and can be mitigated by reducing the GM-CSF dose (and then the GP2 dose, if necessary).

No SAEs were reported in the

GP2 treated patients.

Maximum local and systemic toxicities were primarily grade 1 and grade 2.

Toxicities ranged from redness

at injection site to flu-like symptoms and can be largely attributed to GM-CSF, and not to GP2.

The maximum local and systemic toxicity experienced by patients administered the GP2+GM-CSF vaccine were comparable to those experienced

by patients receiving GM-CSF alone.

For patients receiving GP2 + GM-CSF, maximum local toxicities experienced during the primary

vaccination series were grade 1 (70%), grade 2 (28%), or grade 3 (1%).

The most common toxicities included erythema, induration

and pruritis;

the grade 3 toxicity was induration.

Maximum systemic toxicities were grade 0 (13%), grade 1 (71%), grade 2 (15%),

or grade 3 (1%).

The most common systemic toxicities included fatigue, headache, and myalgias.

The grade 3 toxicity was a diffuse

maculopapular rash.

The toxicities were comparable for patients receiving GM-CSF only, with maximum local toxicities being grade

1 (75%) or grade 2 (25%);

and maximum systemic toxicities being grade 0 (21%), grade 1 (60%), grade 2 (15%), or grade 3 (3%).

The grade 3 systemic toxicities in this group included diffuse urticarial reactions, syncope and extremity pain.

immunotherapy elicited a potent immune response in HLA-A02 patients after they received the 6 primary intradermal injections over

the first 6 months.

The immune response was measured by a local skin test and immunological assays.

Further, booster injections

given every 6 months thereafter prolonged the immune response, thereby providing longer term protection.

response was observed peaking after 6 months compared to baseline, measured by Delayed Type Hypersensitivity ((“DTH”)

skin test using GP2) and immunological assay.

DTH response rate for treated patients is very high.

Orthogonal mean baseline

versus six months:

4.1±1.1mm versus 15.3±

2.2mm (±

standard error).

were administered every 6 months to sustain immunity.

Phase III Trial

are planning to launch a Phase III clinical trial in 2021, using a similar treatment regime as the Phase IIb clinical trial.

manufacturing plan and the Phase III trial protocol have been reviewed by the FDA, and final revisions to the Phase III trial

protocol are under way, which may include an interim analysis/adaptive trial design that will result in the finalization of the

size of the trial.

The primary endpoint of the Phase III clinical trial will compare recurrence rate of GP2 + GM-CSF treated patients

versus placebo patients at various time points using standard of care follow-up.

We believe that it may require up to 2 years

to fully enroll all patients for the trial, and that we may follow-up patients for up to a median 5 years following enrollment

in such trial;

however the addition of an interim analysis may reduce the time required to report clinical data and to file a

BLA application.

These design features of the Phase III clinical trial are currently being finalized by our clinical advisors.

overview of the Phase III clinical trial design is shown below.

have commenced GP2 manufacturing, and we are currently in the process of finalizing our engagement of CMOs and CROs for the Phase

III clinical trial.

Initial & Expandable Breast Cancer Market

believe that the potential market for the proposed initial and follow-on indications is large.

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-A02 allele, while node positive and high risk node negative patients comprise approximately 50% of the market.

we believe that the initial market for GP2 could be the combination of the three populations above which together comprises 6%

of breast cancer patients.

We believe that follow-on indications could include additional HLA types (an additional 30% of the

population) and the low to intermediate expressors of HER2/ neu 1-2+ patients (an additional 50% of all breast cancer

patients) which would expand the GP2 market from our estimated initial 6% to 30% of breast cancer patients who undergo surgery.

Thus the market for GP2, including follow-on indications, could be 2.4 times the current Herceptin adjuvant setting market, which

constitutes approximately 12.5% of breast cancer patients.

believe that the potential market for GP2 could be estimated as follows, with the long term multi-billion dollar annual revenue

potential of GP2 based on 16,750 to 79,800 potential new patients treated per year and Herceptin’s 2018 annual per patient

price of $74,500:

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.

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.

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

intermediate expressors):

HER2/ neu 3+ Positive Over Expressors:

In the 96 HER2/ neu

3+, HLA-A*02 patients, no recurrences were observed in the efficacy population ( p = 0.0338 ).

A patient was in the efficacy population

if they were treated, followed, and remained disease free over the first 6 months, which is the time we believe is required to reach peak

immunity and thus maximum efficacy and protection.

This patient population was treated with GLSI-100 following the first year of trastuzumab

treatment, which followed surgery.

HER2/ neu 1-2+ Low to Intermediate Expressors:

In the 72 HER2/ neu

1-2+, HLA-A*02 patients, no reduction in recurrence rates were observed, but trastuzumab was not administered to these patients.

we may pursue a future trial with GP2 in combination with trastzumab based therapy and other synergistic agents.

5 Year Data Set of GP2 Phase IIb Trial:

HER2 3+ (Positive or Over Expressors)

Patients Who are in the Efficacy Population

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

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.

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

& 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.

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.

Phase III Trial, Flamingo-01

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

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.

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.

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

Breast Cancer Market

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.

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

HER2/ neu 3+ breast cancer patients comprise approximately 25% of all breast cancer patients.

Approximately 40% to 50% of the

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.

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,

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

(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.

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

and maintain market share.

For patients with early stage breast cancer, adjuvant therapy is often given to prevent recurrence

and increase the chance of long-term disease free survival.

Adjuvant therapy for breast cancer can include chemotherapy, hormonal

therapy, radiation therapy, or combinations thereof.

In addition, the HER2 targeted drug Herceptin (trastuzumab) alone or in combination

with Perjeta (pertuzumab), both manufactured and marketed by Roche/Genentech, may be given to patients with tumors with high expression

of HER2/ neu .

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

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.

are a number of approved HER2/ neu targeted therapies, some of which include the following:

Genentech’s Herceptin,

Perjeta and Kadcyla (TDM-1, ado-trastuzumab emtansine);

Puma’s Nerlynx;

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

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

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.

believe that GP2 will act synergistically with Herceptin, Perjeta, Nerlynx, and the newest entrants Kadcyla and Enhertu.

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).

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.

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.

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.

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 subjects for our clinical trials.

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.

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

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.

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.

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

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

We do not have any current contractual arrangements for the manufacture of commercial supplies of our product candidate.

prior clinical trials, GP2 was formulated, filled, labeled, stored, tested, packaged, and distributed to clinical sites by the

pharmacy at the Walter Reed Medical Center and the HJF.

For future clinical trials, we anticipate that GP2 will be formulated,

filled, labeled, stored, tested, packaged, and distributed to clinical sites in licensed cGMP manufacturing facilities as we evaluate

and select primary and secondary facilities which may also serve as commercial facilities.

Jackson Foundation out-licenses technology of the United States military and it conducts research and manages clinical

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 three Phase I and the Phase IIb clinical trials), and possesses all patient

and manufacturing data from such trials.

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

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.

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.

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

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

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.

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.

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.

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

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.

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.

Property Portfolio

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.

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

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

legislative framework, and filing U.S.

and international patent applications on technologies, inventions

and improvements that are important to our business.

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

and other countries, protecting trade secrets, and utilizing regulatory protections such as data exclusivity.

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.

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

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.

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

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.

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.

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.

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

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.

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.

receiving marketing approval.

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.

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.

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:

+ GM-CSF Patent Family —

A patent application has been filed and licensed describing methods and compositions for the

induction of a cytotoxic T-cell response to the GP2 peptide with the effect of inducing and maintaining a protective or therapeutic

immunity against breast cancer.

Patent claims describe the use of the GP2 technology including dosing, formulation, identification

of patients, and use in combination with GM-CSF.

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:

+ GM-CSF Patent Family — A patent application has been filed and licensed describing methods and compositions for the induction

of a cytotoxic T-cell response to the GP2 peptide with the effect of inducing and maintaining a protective or therapeutic immunity

against breast cancer.

Patent claims describe the use of the GP2 technology including dosing, formulation, identification of patients,

and use in combination with GM-CSF.

Patents issued in the U.S.

will expire in 2032 and 2029 and international

patents will expire in 2029.

+ Herceptin Patent Family —

A patent application has been filed and licensed describing methods and compositions of

GP2 peptide in combination with a HER2/ neu targeting antibody such as Herceptin.

and certain foreign patent claims

describe the method and timing of administration.

will expire in 2032 and 2029 and international patents will expire

+ Herceptin Patent Family — A patent application has been filed and licensed describing methods and compositions of GP2 peptide

in combination with a HER2/ neu targeting antibody such as Herceptin.

and certain foreign patent claims describe the method

and timing of administration.

Patents issued in the U.S.

will expire in 2028 and 2026 and international

patents will expire in 2026.

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 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 approval for

the use of our product candidate for one or more indications.

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 10-12 years market exclusivity in the U.S.

will expire in 2028 and 2026 and international patents will expire in 2026.

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.

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 after this offering, and pursuing strategic collaborations to support the future global marketing and sales

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

Strategy —

Including GP2 In Other HER2/ neu -Expressing Cancers

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, the

planned Phase III clinical trial can be supplemented with the following pipeline investments:

efficacy of GP2-GMCSF-Herceptin can be explored in (1) other HLA patients in the same HER2/ neu 3+ breast cancer patient

population, (2) breast cancer patients who are low to intermediate expressors of HER2/ neu (1-2+) and who comprise two-thirds

of the triple negative market, or (3) other HER2/ neu -expressing cancers including, but not limited to, ovarian, gastrointestinal,

and colon cancers.

may acquire a preclinical platform that can be quickly advanced into IND-enabling GMP manufacturing and GLP toxicology studies

followed by initial human clinical trials.

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 studies or seek approval or licensure of our current product candidate or any future product candidates.

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

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.

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

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.

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.

process required by the FDA before biologic product candidates may be marketed in the U.S.

generally involves the following:

of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices,

or GLP, regulations;

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by an independent IRB or ethics committee at each clinical site before the trial is begun;

of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed biologic

product candidate for its intended purpose;

of adequate and well-controlled human clinical trials to establish the safety and efficacy of product;

manufacture of product with adequate controls so that

the product has the purity and potency of the proposed biologic product candidate for its intended purpose;

of and submission to the FDA of a BLA, after completion of all pivotal clinical trials;

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determination by the FDA within 60 days of its receipt of a BLA to file the application for review;

completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is

produced to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the

biological product’s continued safety, purity and potency, and of selected clinical investigations to assess compliance

review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the U.S.,

which must be updated annually when significant changes are made.

testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals

for our current product candidate or any future product candidates will be granted on a timely basis, if at all.

Prior to beginning

the first clinical trial with a product candidate, we must submit an IND to the FDA.

An IND is a request for authorization from

the FDA to administer an investigational new drug product to humans.

The central focus of an IND submission is on the general

investigational plan and the protocol(s) for clinical studies.

The IND also includes results of animal and in vitro studies assessing

the toxicology, pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product;

chemistry, manufacturing,

and controls information;

completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced

to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the biological product’s

continued safety, purity and potency, and of selected clinical investigations to assess compliance with GCP;

review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the U.S., which

must be updated annually when significant changes are made.

testing and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for

our current product candidate or any future product candidates will be granted on a timely basis, if at all.

Prior to beginning the first

clinical trial with a product candidate, a sponsor must submit an IND to the FDA.

An IND is a request for authorization from the

FDA to administer an investigational new drug product to humans.

The central focus of an IND submission is on the general investigational

plan and the protocol(s) for clinical trials.

The IND also includes results of animal and in vitro studies assessing the toxicology,

pharmacokinetics, pharmacology, and pharmacodynamic characteristics of the product;

chemistry, manufacturing, and controls information;

and any available human data or literature to support the use of the investigational product.

must become effective before human clinical trials may begin.

The IND automatically becomes effective 30 days after receipt by

the FDA, unless the FDA, within the 30-day time period, raises safety concerns or questions about the proposed clinical trial.

In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve any outstanding concerns or

questions before the clinical trial can begin.

Submission of an IND therefore may or may not result in FDA authorization to begin

a clinical trial.

trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators

in accordance with GCP, which include the requirement that all research subjects provide their informed consent for their participation

An IND must become effective before human

clinical trials may begin.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day

time period, raises safety concerns or questions about the proposed clinical trial.

In such a case, the IND may be placed on clinical

hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin.

of an IND therefore may or may not result in FDA authorization to begin a clinical trial.

trials involve the administration of the investigational product to human patients under the supervision of qualified investigators

in accordance with GCP, which include the requirement that all research patients provide their informed consent for their participation

in any clinical trial.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical

trial, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

A separate submission to

the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol

Furthermore, an IRB for each site proposing to conduct the clinical trial must review and approve the plan for any

clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the clinical trial

until completed.

Regulatory authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including

a finding that the subjects are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated

Some studies also include oversight by a Data and Safety Monitoring Board, or DSMB, organized by the clinical trial

sponsor, which provides authorization for whether or not a clinical trial may move forward at designated check points based on

access to certain data from the clinical trial and may halt the clinical trial if it determines that there is an unacceptable

safety risk for subjects or other grounds, such as no demonstration of efficacy.

There are also requirements governing the reporting

of ongoing clinical studies and clinical trial results to public registries.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial,

the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.

A separate submission to the existing

IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.

Furthermore, an IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and

its informed consent form before the clinical trial begins at that site and must monitor the clinical trial until completed.

authorities, the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the patients

are being exposed to an unacceptable health risk or that the trial is unlikely to meet its stated objectives.

Some clinical trials

also include oversight by a Data and Safety Monitoring Board, or DSMB, organized by the clinical trial sponsor, which provides authorization

for whether or not a clinical trial may move forward at designated check points based on access to certain data from the clinical trial

and may halt the clinical trial if it determines that there is an unacceptable safety risk for patients or other grounds, such

as no demonstration of efficacy.

There are also requirements governing the reporting of ongoing clinical trials and clinical trial

results to public registries.

purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap.

The investigational product is initially introduced into healthy human subjects or patients with the target

1 — The investigational product is initially introduced into healthy human patients or patients with the target

disease or condition.

These studies are designed to test the safety, dosage tolerance, absorption, metabolism and distribution

of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain early

evidence on effectiveness.

The investigational product is administered to a limited patient population with a specified disease or condition

to evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and

safety risks.

Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive

Phase 3 clinical trials.

The investigational product is administered to an expanded patient population to further evaluate dosage, to

provide statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically

dispersed clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit ratio of the investigational

product and to provide an adequate basis for product approval.

In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a

product is approved to gain more information about the product.

These so-called Phase 4 studies may be made a condition to

These clinical trials are designed to test the safety, dosage tolerance, absorption, metabolism and

distribution of the investigational product in humans, the side effects associated with increasing doses, and, if possible, to gain

early evidence on effectiveness.

2 — The investigational product is administered to a limited patient population with a specified disease or condition to

evaluate the preliminary efficacy, optimal dosages and dosing schedule and to identify possible adverse side effects and safety risks.

Multiple Phase 2 clinical trials may be conducted to obtain information prior to beginning larger and more expensive Phase 3 clinical

3 — The investigational product is administered to an expanded patient population to further evaluate dosage, to provide

statistically significant evidence of clinical efficacy and to further test for safety, generally at multiple geographically dispersed

clinical trial sites.

These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product

and to provide an adequate basis for product approval.

4 — In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product

is approved to gain more information about the product.

These so-called Phase 4 clinical trials may be made a condition to

approval of the BLA.

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that the data collected will support FDA approval or licensure of the product.

Concurrent with clinical trials, companies may

complete additional animal studies and develop additional information about the biological characteristics of the product candidate

and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing

process must be capable of consistently producing quality batches of the product candidate and, among other things, must develop

methods for testing the identity, strength, quality and purity of the final product, or for biologics, the safety, purity and

Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate

that the product candidate does not undergo unacceptable deterioration over its shelf life.

Concurrent with clinical trials, companies may complete

additional animal studies and develop additional information about the biological characteristics of the product candidate and must finalize

a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.

The manufacturing process must

be capable of consistently producing quality batches of the product candidate and, among other things, must develop methods for testing

the identity, strength, quality and purity of the final product, or for biologics, the safety, purity and potency.

Additionally, appropriate

packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo

unacceptable deterioration over its shelf life.

Submission and Review by the FDA

successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product

development, nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the

product for one or more indications.

The BLA must include all relevant data available from pertinent preclinical and clinical

studies, including negative or ambiguous results as well as positive findings, together with detailed information relating to

the product’s chemistry, manufacturing, controls, and proposed labeling, among other things.

Data can come from company-sponsored

clinical studies intended to test the safety and effectiveness of a use of the product, or from a number of alternative sources,

including studies initiated by investigators.

The submission of a BLA requires payment of a substantial user fee to FDA, and the

sponsor of an approved BLA is also subject to annual product and establishment user fees.

successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development,

nonclinical studies and clinical trials are submitted to the FDA as part of a BLA requesting approval to market the product for one or

more indications.

The BLA must include all relevant data available from pertinent preclinical studies and clinical trials, including

negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s chemistry,

manufacturing, controls, and proposed labeling, among other things.

Data can come from company-sponsored clinical trials intended

to test the safety and effectiveness of a use of the product, or from a number of alternative sources, including clinical trials

initiated by investigators.

The submission of a BLA requires payment of a substantial user fee to FDA, and the sponsor of an approved

BLA is also subject to annual product and establishment user fees.

These fees are typically increased annually.

A waiver of user fees may be obtained under certain limited circumstances.

a BLA has been submitted, the FDA’s goal is to review the application within ten months after it accepts the application

for filing, or, if the application relates to an unmet medical need in a serious or life-threatening indication, six months after

the FDA accepts the application for filing.

The review process is often significantly extended by FDA requests for additional

information or clarification.

The FDA reviews a BLA to determine, among other things, whether a product is safe, pure and potent

and the facility in which it is manufactured, processed, packed, or held meets standards designed to assure the product’s

continued safety, purity and potency.

The FDA may convene an advisory committee to provide clinical insight on application review

Before approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance

with cGMP requirements and adequate to assure consistent production of the product within required specifications.

determines that the application, manufacturing process or manufacturing facilities are not acceptable, it will outline the deficiencies

in the submission and often will request additional testing or information.

Notwithstanding the submission of any requested additional

information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.

A waiver of user fees

may be obtained under certain limited circumstances.

a BLA has been submitted, the FDA’s goal is to review the application within ten months after it accepts the application for filing,

or, if the application relates to an unmet medical need in a serious or life-threatening indication, six months after the FDA accepts

the application for filing.

The review process is often significantly extended by FDA requests for additional information or clarification.

The FDA reviews a BLA to determine, among other things, whether a product is safe, pure and potent and the facility in which it is manufactured,

processed, packed, or held meets standards designed to assure the product’s continued safety, purity and potency.

The FDA may convene

an advisory committee to provide clinical insight on application review questions.

Before approving a BLA, the FDA will typically inspect

the facility or facilities where the product is manufactured.

The FDA will not approve an application unless it determines that the manufacturing

processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within

required specifications.

If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable,

it will outline the deficiencies in the submission and often will request additional testing or information.

Notwithstanding the submission

of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria

for approval.

testing and approval process requires substantial time, effort and financial resources, and each may take several years to complete.

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to secure necessary governmental approvals, which could delay or preclude us from marketing our product.

After the FDA evaluates

a BLA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be

produced, the FDA may issue an approval letter or a Complete Response Letter.

An approval letter authorizes commercial marketing

of the product with specific prescribing

information for specific indications.

A Complete Response Letter indicates that the review cycle of the application is complete

and the application is not ready for approval.

After the FDA evaluates a BLA

and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the

FDA may issue an approval letter or a Complete Response Letter.

An approval letter authorizes commercial marketing of the product with

specific prescribing information for specific indications.

A Complete Response Letter indicates that the review cycle of the application

is complete and the application is not ready for approval.

A Complete Response Letter may request additional information or clarification.

The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied, require additional testing

or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

regulatory approval of a product is granted, such approval may entail limitations on the indicated uses for which such product

may be marketed.

For example, the FDA may approve the BLA with a Risk Evaluation and Mitigation Strategy, or REMS, plan to mitigate

risks, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted

distribution methods, patient registries and other risk minimization tools.

The FDA also may condition approval on, among other

things, changes to proposed labeling or the development of adequate controls and specifications.

Once approved, the FDA may withdraw

the product approval if compliance with pre- and post-marketing regulatory standards is not maintained or if problems occur after

the product reaches the marketplace.

The FDA may require one or more Phase 4 post-market studies and surveillance to further assess

and monitor the product’s safety and effectiveness after commercialization and may limit further marketing of the product

based on the results of these post-marketing studies.

In addition, new government requirements, including those resulting from

new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval

of our product under development.

sponsor may seek approval of its product candidate under programs designed to accelerate FDA’s review and approval of new

drugs and biological products that meet certain criteria.

Specifically, new drugs and biological products are eligible for Fast

Track designation if they are intended to treat a serious or life-threatening condition and demonstrate the potential to address

unmet medical needs for the condition.

For a product candidate with Fast Track designation, the FDA may consider sections of the

BLA for review on a rolling basis before the complete application is submitted if relevant criteria are met.

A Fast Track designated

product candidate may also qualify for priority review, under which the FDA sets the target date for FDA action on the BLA at

six months after the FDA accepts the application for filing.

Priority review is granted when there is evidence that the proposed

product would be a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious

If criteria are not met for priority review, the application is subject to the standard FDA review period of 10 months

after FDA accepts the application for filing.

Priority review designation does not change the scientific/medical standard for

approval or the quality of evidence necessary to support approval.

the Accelerated Approval program, the FDA may approve a BLA on the basis of either a surrogate endpoint that is reasonably likely

to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality,

that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account

the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

Post-marketing studies

or completion of ongoing studies after marketing approval are generally required to verify the biologic’s clinical benefit

in relationship to the surrogate endpoint or ultimate outcome in relationship to the clinical benefit.

The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied, require additional testing or information

and/or require post-marketing testing and surveillance to monitor safety or efficacy of a product.

regulatory approval of a product is granted, such approval may entail limitations on the indicated uses for which such product may be

For example, the FDA may approve the BLA with a Risk Evaluation and Mitigation Strategy, or REMS, plan to mitigate risks, which

could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods,

patient registries and other risk minimization tools.

The FDA also may condition approval on, among other things, changes to proposed

labeling or the development of adequate controls and specifications.

Once approved, the FDA may withdraw the product approval if compliance

with pre- and post-marketing regulatory standards is not maintained or if problems occur after the product reaches the marketplace.

FDA may require one or more Phase 4 post-market clinical trials and surveillance to further assess and monitor the product’s

safety and effectiveness after commercialization and may limit further marketing of the product based on the results of these post-marketing

clinical trials.

In addition, new government requirements, including those resulting from new legislation, may be established,

or the FDA’s policies may change, which could delay or prevent regulatory approval of our product under development.

sponsor may seek approval of its product candidate under programs designed to accelerate FDA’s review and approval of new drugs

and biological products that meet certain criteria.

Specifically, new drugs and biological products are eligible for Fast Track designation

if they are intended to treat a serious or life-threatening condition and demonstrate the potential to address unmet medical needs for

the condition.

For a product candidate with Fast Track designation, the FDA may consider sections of the BLA for review on a rolling

basis before the complete application is submitted if relevant criteria are met.

A Fast Track designated product candidate may also qualify

for priority review, under which the FDA sets the target date for FDA action on the BLA at six months after the FDA accepts the application

Priority review is granted when there is evidence that the proposed product would be a significant improvement in the safety

or effectiveness of the treatment, diagnosis, or prevention of a serious condition.

If criteria are not met for priority review, the

application is subject to the standard FDA review period of 10 months after FDA accepts the application for filing.

Priority review designation

does not change the scientific/medical standard for approval or the quality of evidence necessary to support approval.

the Accelerated Approval program, the FDA may approve a BLA on the basis of either a surrogate endpoint that is reasonably likely to

predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably

likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity,

or prevalence of the condition and the availability or lack of alternative treatments.

Post-marketing clinical trials or completion

of ongoing clinical trials after marketing approval are generally required to verify the biologic’s clinical benefit in

relationship to the surrogate endpoint or ultimate outcome in relationship to the clinical benefit.

addition, a sponsor may seek FDA designation of its product candidate as a Breakthrough Therapy, if the product candidate is intended,

alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition

and preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over existing therapies on

one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

the FDA designates a breakthrough therapy, it may take actions appropriate to expedite the development and review of the application.

Breakthrough designation also allows the sponsor to file sections of the BLA for review on a rolling basis.

alone or in combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition and preliminary

clinical evidence indicates that the therapy may demonstrate substantial improvement over existing therapies on one or more clinically

significant endpoints, such as substantial treatment effects observed early in clinical development.

If the FDA designates a breakthrough

therapy, it may take actions appropriate to expedite the development and review of the application.

Breakthrough designation also allows

the sponsor to file sections of the BLA for review on a rolling basis.

Track, Priority Review and Breakthrough Therapy designations do not change the standards for approval but may expedite the development

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Healthcare Laws and Compliance Requirements

sales, promotion, medical education and other activities following product approval will be subject to regulation by numerous

regulatory and law enforcement authorities in the U.S.

in addition to FDA, including potentially the Federal Trade Commission,

the Department of Justice, the Centers for Medicare and Medicaid Services, other divisions of the Department of Health and Human

Services and state and local governments.

Our promotional and scientific/educational

programs must comply with the federal Anti-Kickback Statute, the Foreign Corrupt Practices Act, the False Claims Act, or FCA,

the Veterans Health Care Act, physician payment transparency laws, privacy laws, security laws, and additional state laws similar

to the foregoing.

federal Anti-Kickback Statute prohibits, among other things, the offer, receipt, or payment of remuneration in exchange for or

to induce the referral of patients or the use of products or services that would be paid for in whole or part by Medicare, Medicaid

or other federal health care programs.

Remuneration has been broadly defined to include anything of value, including cash, improper

discounts, and free or reduced price items and services.

The government has enforced the Anti-Kickback Statute to reach large

settlements with healthcare companies based on sham research or consulting and other financial arrangements with physicians.

a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a

In addition, the government may assert that a claim including items or services resulting from a violation of the federal

Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA.

Many states have similar laws that apply

to their state health care programs as well as private payors.

FCA imposes liability on persons who, among other things, present or cause to be presented false or fraudulent claims for payment

by a federal health care program.

The FCA has been used to prosecute persons submitting claims for payment that are inaccurate

or fraudulent, that are for services not provided as claimed, or for services that are not medically necessary.

Actions under

the FCA may be brought by the Attorney General or as a qui tam action by a private individual in the name of the government.

of the FCA can result in significant monetary penalties and treble damages.

The federal government is using the FCA, and the accompanying

threat of significant liability, in its investigation and prosecution of pharmaceutical and biotechnology companies throughout

the country, for example, in connection with the promotion of products for unapproved uses and other sales and marketing practices.

The government has obtained multi-million and multibillion dollar settlements under the FCA in addition to individual criminal

convictions under applicable criminal statutes.

In addition, companies have been forced to implement extensive corrective action

plans, and have often become subject to consent decrees or corporate integrity agreements, restricting the manner in which they

conduct their business.

The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, also created federal

criminal statutes that prohibit, among other things, knowingly and willfully executing a scheme to defraud any healthcare benefit

program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up a material fact

or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare

benefits, items or services.

Given the significant size of actual and potential settlements, it is expected that the government

will continue to devote substantial resources to investigating healthcare providers’

and manufacturers’

with applicable fraud and abuse laws.

sales, promotion, medical education and other activities following product approval will be subject to regulation by numerous regulatory

and law enforcement authorities in the U.S.

in addition to FDA, including potentially the Federal Trade Commission, the Department of

Justice, the Centers for Medicare and Medicaid Services, other divisions of the Department of Health and Human Services and state and

local governments.

Our promotional and scientific/educational programs must comply with the federal Anti-Kickback Statute, the Foreign

Corrupt Practices Act, the False Claims Act, or FCA, the Veterans Health Care Act, physician payment transparency laws, privacy laws,

security laws, and additional state laws similar to the foregoing.

federal Anti-Kickback Statute prohibits, among other things, the offer, receipt, or payment of remuneration in exchange for or to induce

the referral of patients or the use of products or services that would be paid for in whole or part by Medicare, Medicaid or other federal

health care programs.

Remuneration has been broadly defined to include anything of value, including cash, improper discounts, and free

or reduced price items and services.

The government has enforced the Anti-Kickback Statute to reach large settlements with healthcare

companies based on sham research or consulting and other financial arrangements with physicians.

Further, a person or entity does not

need to have actual knowledge of the statute or specific intent to violate it to have committed a violation.

In addition, the government

may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false

or fraudulent claim for purposes of the FCA.

Many states have similar laws that apply to their state health care programs as well as

private payors.

FCA imposes liability on persons who, among other things, present or cause to be presented false or fraudulent claims for payment by

a federal health care program.

The FCA has been used to prosecute persons submitting claims for payment that are inaccurate or fraudulent,

that are for services not provided as claimed, or for services that are not medically necessary.

Actions under the FCA may be brought

by the Attorney General or as a qui tam action by a private individual in the name of the government.

Violations of the FCA can result

in significant monetary penalties and treble damages.

The federal government is using the FCA, and the accompanying threat of significant

liability, in its investigation and prosecution of pharmaceutical and biotechnology companies throughout the country, for example, in

connection with the promotion of products for unapproved uses and other sales and marketing practices.

The government has obtained multi-million

and multibillion dollar settlements under the FCA in addition to individual criminal convictions under applicable criminal statutes.

In addition, companies have been forced to implement extensive corrective action plans, and have often become subject to consent decrees

or corporate integrity agreements, restricting the manner in which they conduct their business.

The federal Health Insurance Portability

and Accountability Act of 1996, or HIPAA, also created federal criminal statutes that prohibit, among other things, knowingly and willfully

executing a scheme to defraud any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying,

concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery

of or payment for healthcare benefits, items or services.

Given the significant size of actual and potential settlements, it is expected

that the government will continue to devote substantial resources to investigating healthcare providers’ and manufacturers’

compliance with applicable fraud and abuse laws.

addition, there has been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or

collectively, the Affordable Care Act, among other things, imposed new reporting requirements on drug manufacturers for payments

or other transfers of value made by them to physicians and teaching hospitals, as well as ownership and investment interests held

by physicians and their immediate family members.

The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively,

the Affordable Care Act, among other things, imposed new reporting requirements on drug manufacturers for payments or other transfers

of value made by them to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their

immediate family members.

Failure to submit required information may result in civil monetary penalties .

Certain states also mandate implementation of commercial compliance programs, impose restrictions on drug manufacturer marketing

practices and/or require the tracking and reporting of gifts, compensation and other remuneration to physicians and other healthcare

professionals.

may also be subject to data privacy and security regulation by both the federal government and the states in which it conducts

its business.

HIPAA, as amended by HITECH, and their respective implementing regulations, imposes specified requirements relating

to the privacy, security and transmission of individually identifiable health information.

Among other things, HITECH makes HIPAA’s

privacy and security standards directly applicable to “business associates,”

defined as independent contractors or

agents of covered entities that create, receive, maintain or transmit protected health information in connection with providing

a service for or on behalf of a covered entity.

HITECH also increased the civil and criminal penalties that may be imposed against

covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil

actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs

associated with pursuing federal civil actions.

In addition, state laws govern the privacy and security of health information

in certain circumstances, many of which differ from each other in significant ways and may not have the same effect.

our operations are found to be in violation of any of such laws or any other governmental regulations that apply to it, we may

be subject to penalties, including, without limitation, civil and criminal penalties, damages, fines, the curtailment or restructuring

of our operations, exclusion from participation in federal and state healthcare programs and imprisonment, any of which could

adversely affect our ability to operate our business and our financial results.

Certain states also mandate

implementation of commercial compliance programs, impose restrictions on drug manufacturer marketing practices and/or require the tracking

and reporting of gifts, compensation and other remuneration to physicians and other healthcare professionals.

may also be subject to data privacy and security regulation by both the federal government and the states in which it conducts its business.

HIPAA, as amended by HITECH, and their respective implementing regulations, imposes specified requirements relating to the privacy, security

and transmission of individually identifiable health information.

Among other things, HITECH makes HIPAA’s privacy and security

standards directly applicable to “business associates,” defined as independent contractors or agents of covered entities

that create, receive, maintain or transmit protected health information in connection with providing a service for or on behalf of a

covered entity.

HITECH also increased the civil and criminal penalties that may be imposed against covered entities, business associates

and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal

courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions.

addition, state laws govern the privacy and security of health information in certain circumstances, many of which differ from each other

in significant ways and may not have the same effect.

our operations are found to be in violation of any of such laws or any other governmental regulations that apply to it, we may be subject

to penalties, including, without limitation, civil and criminal penalties, damages, fines, the curtailment or restructuring of our operations,

exclusion from participation in federal and state healthcare programs and imprisonment, any of which could adversely affect our ability

to operate our business and our financial results.

Foreign Corrupt Practices Act and similar worldwide anti-bribery laws generally prohibit companies and their intermediaries

from making improper payments to foreign officials for the purpose of obtaining or retaining business.

We cannot assure you that

our internal control policies and procedures will protect us from reckless or negligent acts committed by our employees, future

distributors, partners, collaborators or agents.

Violations of these laws, or allegations of such violations, could result in

fines, penalties or prosecution and have a negative impact on our business, results of operations and reputation.

We cannot assure you that our

internal control policies and procedures will protect us from reckless or negligent acts committed by our employees, future distributors,

partners, collaborators or agents.

Violations of these laws, or allegations of such violations, could result in fines, penalties or prosecution

and have a negative impact on our business, results of operations and reputation.

and Reimbursement

of pharmaceutical products depend significantly on the availability of third-party coverage and reimbursement.

Third-party payors

include government health administrative authorities, managed care providers, private health insurers and other organizations.

Although we currently believe that third-party payors will provide coverage and reimbursement for our product candidate, if approved,

these third-party payors are increasingly challenging the price and examining the cost-effectiveness of medical products and services.

In addition, significant uncertainty exists as to the reimbursement status of newly approved healthcare products.

to conduct expensive clinical studies to demonstrate the comparative cost-effectiveness of our product candidate.

Seeking coverage

and reimbursement from third-party payors can be time consuming and expensive.

Moreover, a payor’s decision to provide coverage

for a drug product does not imply that an adequate reimbursement rate will be approved.

Reimbursement may not be available or

sufficient to allow us to sell our product on a competitive and profitable basis.

addition to regulations in the U.S., we are and will be subject, either directly or through our distribution partners, to a variety

of regulations in other jurisdictions governing, among other things, clinical trials and commercial sales and distribution of

our product, if approved.

Third-party payors include

government health administrative authorities, managed care providers, private health insurers and other organizations.

Although we currently

believe that third-party payors will provide coverage and reimbursement for our product candidate, if approved, these third-party payors

are increasingly challenging the price and examining the cost-effectiveness of medical products and services.

In addition, significant

uncertainty exists as to the reimbursement status of newly approved healthcare products.

We may need to conduct expensive clinical trials

to demonstrate the comparative cost-effectiveness of our product candidate.

Seeking coverage and reimbursement from third-party payors

can be time consuming and expensive.

Moreover, a payor’s decision to provide coverage for a drug product does not imply that an

adequate reimbursement rate will be approved.

Reimbursement may not be available or sufficient to allow us to sell our product on a competitive

and profitable basis.

addition to regulations in the U.S., we are and will be subject, either directly or through our distribution partners, to a variety of

regulations in other jurisdictions governing, among other things, clinical trials and commercial sales and distribution of our product,

or not we obtain FDA approval for a product, we must obtain the requisite approvals from regulatory authorities in non-U.S.

prior to the commencement of clinical trials or marketing of the product in those countries.

Certain countries outside of the

have processes that require the submission of a clinical trial application much like an IND prior to the commencement of

human clinical trials.

In Europe, for example, a clinical trial application, or CTA, must be submitted to the competent national

health authority and to independent ethics committees in each country in which a company plans to conduct clinical trials.

the CTA is approved in accordance with a country’s requirements, clinical trials may proceed in that country.

requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country

to country, even though there is already some degree of legal harmonization in the European Union member states resulting from

the national implementation of underlying E.U.

In all cases, the clinical trials are conducted in accordance with

GCP and other applicable regulatory requirements.

obtain regulatory approval of a new drug or medicinal product in the European Union, a sponsor must obtain approval of a marketing

authorization application.

The way in which a medicinal product can be approved in the European Union depends on the nature of

the medicinal product.

centralized procedure results in a single marketing authorization granted by the European Commission that is valid across the

European Union, as well as in Iceland, Liechtenstein and Norway.

The centralized procedure is compulsory for human drugs that

(i) derived from biotechnology processes, such as genetic engineering, (ii) contain a new active substance indicated for

the treatment of certain diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune

dysfunctions and viral diseases, (iii) officially designated as “orphan drugs”

and (iv) advanced-therapy medicines,

such as gene-therapy, somatic cell-therapy or tissue-engineered medicines.

The centralized procedure may, at the request of the

applicant, also be used for human drugs which do not fall within the above mentioned categories if the human drug (a) contains

a new active substance which was not authorized in the European Community;

or (b) the applicant shows that the medicinal product

constitutes a significant therapeutic, scientific or technical innovation or that the granting of authorization in the centralized

procedure is in the interests of patients or animal health at the European Community level.

the centralized procedure in the European Union, the maximum timeframe for the evaluation of a marketing authorization application

by the EMA is 210 days (excluding clock stops, when additional written or oral information is to be provided by the applicant

in response to questions asked by the Committee for Medicinal Products for Human Use, or CHMP), with adoption of the actual marketing

authorization by the European Commission thereafter.

Accelerated evaluation might be granted by the CHMP in exceptional cases,

when a medicinal product is expected to be of a major public health interest from the point of view of therapeutic innovation,

defined by three cumulative criteria:

Certain countries outside of the U.S.

processes that require the submission of a clinical trial application much like an IND prior to the commencement of human clinical trials.

In Europe, for example, a clinical trial application, or CTA, must be submitted to the competent national health authority and to independent

ethics committees in each country in which a company plans to conduct clinical trials.

Once the CTA is approved in accordance with a

country’s requirements, clinical trials may proceed in that country.

requirements and process governing the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to

country, even though there is already some degree of legal harmonization in the European Union member states resulting from the national

implementation of underlying E.U.

In all cases, the clinical trials are conducted in accordance with GCP and other applicable

regulatory requirements.

obtain regulatory approval of a new drug or medicinal product in the European Union, a sponsor must obtain approval of a marketing authorization

The way in which a medicinal product can be approved in the European Union depends on the nature of the medicinal product.

centralized procedure results in a single marketing authorization granted by the European Commission that is valid across the European

Union, as well as in Iceland, Liechtenstein and Norway.

The centralized procedure is compulsory for human drugs that are:

from biotechnology processes, such as genetic engineering, (ii) contain a new active substance indicated for the treatment of certain

diseases, such as HIV/AIDS, cancer, diabetes, neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases,

(iii) officially designated as “orphan drugs” and (iv) advanced-therapy medicines, such as gene-therapy, somatic cell-therapy

or tissue-engineered medicines.

The centralized procedure may, at the request of the applicant, also be used for human drugs which do

not fall within the above mentioned categories if the human drug (a) contains a new active substance which was not authorized in the

European Community;

or (b) the applicant shows that the medicinal product constitutes a significant therapeutic, scientific or technical

innovation or that the granting of authorization in the centralized procedure is in the interests of patients or animal health at the

European Community level.

the centralized procedure in the European Union, the maximum timeframe for the evaluation of a marketing authorization application by

the EMA is 210 days (excluding clock stops, when additional written or oral information is to be provided by the applicant in response

to questions asked by the Committee for Medicinal Products for Human Use, or CHMP), with adoption of the actual marketing authorization

by the European Commission thereafter.

Accelerated evaluation might be granted by the CHMP in exceptional cases, when a medicinal product

is expected to be of a major public health interest from the point of view of therapeutic innovation, defined by three cumulative criteria:

the seriousness of the disease to be treated;

the absence of an appropriate alternative

therapeutic approach, and anticipation of exceptional high therapeutic benefit.

In this circumstance, EMA ensures that the evaluation

for the opinion of the CHMP is completed within 150 days and the opinion issued thereafter.

mutual recognition procedure, or MRP, for the approval of human drugs is an alternative approach to facilitate individual national

marketing authorizations within the European Union.

The MRP may be applied for all human drugs for which the centralized procedure

is not obligatory.

The MRP is applicable to the majority of conventional medicinal products, and is based on the principle of

recognition of an already existing national marketing authorization by one or more member states.

characteristic of the MRP is that the procedure builds on an already existing marketing authorization in a member state of the

that is used as reference in order to obtain marketing authorizations in other E.U.

the absence of an appropriate alternative therapeutic approach, and anticipation of exceptional

high therapeutic benefit.

In this circumstance, EMA ensures that the evaluation for the opinion of the CHMP is completed within 150 days

and the opinion issued thereafter.

mutual recognition procedure, or MRP, for the approval of human drugs is an alternative approach to facilitate individual national marketing

authorizations within the European Union.

The MRP may be applied for all human drugs for which the centralized procedure is not obligatory.

The MRP is applicable to the majority of conventional medicinal products, and is based on the principle of recognition of an already

existing national marketing authorization by one or more member states.

characteristic of the MRP is that the procedure builds on an already existing marketing authorization in a member state of the E.U.

is used as reference in order to obtain marketing authorizations in other E.U.

member states.

In the MRP, a marketing

authorization for a drug already exists in one or more member states of the E.U.

and subsequently marketing authorization applications

are made in other European Union member states by referring to the initial marketing authorization.

The member state in which

the marketing authorization was first granted will then act as the reference member state.

The member states where the marketing

authorization is subsequently applied for act as concerned member states.

MRP is based on the principle of the mutual recognition by European Union member states of their respective national marketing

authorizations.

Based on a marketing authorization in the reference member state, the applicant may apply for marketing authorizations

in other member states.

In such case, the reference member state shall update its existing assessment report about the drug in

After the assessment is completed, copies of the report are sent to all member states, together with the approved summary

In the MRP, a marketing authorization for

a drug already exists in one or more member states of the E.U.

and subsequently marketing authorization applications are made in other

European Union member states by referring to the initial marketing authorization.

The member state in which the marketing authorization

was first granted will then act as the reference member state.

The member states where the marketing authorization is subsequently applied

for act as concerned member states.

MRP is based on the principle of the mutual recognition by European Union member states of their respective national marketing authorizations.

Based on a marketing authorization in the reference member state, the applicant may apply for marketing authorizations in other member

In such case, the reference member state shall update its existing assessment report about the drug in 90 days.

After the assessment

is completed, copies of the report are sent to all member states, together with the approved summary of product characteristics, labeling

and package leaflet.

The concerned member states then have 90 days to recognize the decision of the reference member state and the summary

of product characteristics, labeling and package leaflet.

The concerned member states then have 90 days to recognize the decision

of the reference member state and the summary of product characteristics, labeling and package leaflet.

National marketing authorizations

shall be granted within 30 days after acknowledgement of the agreement.

any Member State refuse to recognize the marketing authorization by the reference member state, on the grounds of potential serious

risk to public health, the issue will be referred to a coordination group.

Within a timeframe of 60 days, member states shall,

within the coordination group, make all efforts to reach a consensus.

If this fails, the procedure is submitted to an EMA scientific

committee for arbitration.

The opinion of this EMA Committee is then forwarded to the Commission, for the start of the decision-making

As in the centralized procedure, this process entails consulting various European Commission Directorates General and

the Standing Committee on Human Medicinal Products or Veterinary Medicinal Products, as appropriate.

National marketing authorizations shall be granted within 30 days after acknowledgement

of the agreement.

any Member State refuse to recognize the marketing authorization by the reference member state, on the grounds of potential serious risk

to public health, the issue will be referred to a coordination group.

Within a timeframe of 60 days, member states shall, within the

coordination group, make all efforts to reach a consensus.

If this fails, the procedure is submitted to an EMA scientific committee for

The opinion of this EMA Committee is then forwarded to the Commission, for the start of the decision-making process.

in the centralized procedure, this process entails consulting various European Commission Directorates General and the Standing Committee

on Human Medicinal Products or Veterinary Medicinal Products, as appropriate.

other countries outside of the European Union, such as countries in Eastern Europe, Latin America or Asia, the requirements governing

the conduct of clinical trials, product licensing, pricing and reimbursement vary from country to country.

In all cases, again,

the clinical trials are conducted in accordance with GCP and the other applicable regulatory requirements.

we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension

of clinical trials, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions

and criminal prosecution.

In all cases, again, the clinical

trials are conducted in accordance with GCP and the other applicable regulatory requirements.

we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension of clinical

trials, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Capital Management

of March 21, 2022 we had 3 full-time employee and 3 part-time employees.

We are not a party to any collective

bargaining agreements.

We are not a party to any collective bargaining

We believe that we maintain good relations with our employees.

We do not have any

employees that are represented by a labor union or covered under a collective bargaining agreement.

Our future success depends

on our ability to attract, develop and retain key personnel, maintain our culture, and ensure diversity and inclusion in our board, management

and broader workforce.

Our human resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating

our existing and additional employees.

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 1. Business