What changed in this filing

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Item 1. Business

2024-04-15 compared with 2023-03-31 · 95 added, 52 removed, 758 unchanged (16% of the section changed)

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.

are a clinical-stage biopharmaceutical company focused on our Phase III clinical

trial, Flamingo-01, which is evaluating GLSI-100, an immunotherapy to prevent breast cancer recurrences.

GP2 is a 9 amino acid transmembrane peptide of the HER2/neu protein, a cell surface

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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.

have commenced Flamingo-01, a Phase III clinical trial with Baylor College of Medicine as the global primary investigator site.

have commenced Flamingo-01, a Phase III clinical trial, with plans to expand into Europe and to open up to 150 sites globally.

is designed to evaluate the safety and efficacy of GLSI-100 in HER2 /neu positive patients with residual disease or high-risk pathologic

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Phase IIb Clinical Trial Overview

II Clinical Trial Study Report:

We are preparing a comprehensive study report of the Phase II trial for the FDA prior to the filing

This report will include the patients with breast cancer recurrences, the last known date of patients who did not recur (censoring

data), the adverse events, immune responses, and other final study report analyses.

This report will serve to complement the Phase III

data and to provide a drug product dossier that can also be submitted to regulatory agencies in other countries for marketing approval.

The use of GM-CSF as an adjuvant in GLSI-100 may also be included in the dossier as GM-CSF is only commercially available in the US at

have experienced significant interest from investors, strategics, analysts, and regulators in the 5 year follow-up data we published

and the 3 and 4 year follow-up data independently published by the clinical investigators.

The differences between these publications

can be best explained by the increased maturity of the data as each year progressed.

In all 3 publications, no recurrences or a 100%

reduction in recurrence rate, were reported in the sub-population that the Flamingo-01 design has been based on and any differences between

the number of patients in the treated or placebo groups has been shown to be immaterial.

did not have responsibility for the conduct of the trial or for the data from the Phase II trial.

After the trial had already started,

we received the rights to the Phase II trial data pursuant to a license agreement with the Henry Jackson Foundation (HJF) that entitled

us to all of the GP2 data from the Phase II trial and all prior trials, but did not provide us with the ability to participate in the

Phase II trial as a regulatory clinical sponsor.

The lead clinicians and HJF were responsible for project and site management, medical

monitoring, data monitoring of case report forms (CRFs), correspondence with the FDA, and creation, data entry and management of the

We were provided study updates but were not provided an opportunity to participate in any of the above activities or to review

the publications of the 3 and 4 year follow-up data by the lead clinicians.

Thus, the comprehensive study report will rely on cooperation

from HJF and the clinical sites who are responsible for providing the final data accurately to us.

are currently comparing the final CRFs and database provided by HJF and have noted the following inconsistencies as the comprehensive

study report is being prepared.

The lead clinicians reported in an annual report to the FDA and in their publication of 4 year follow-up

data a 6th recurrence in the HER2 positive control arm of the study.

We conservatively chose not to report this 6th recurrence since

it was not reported in the data provided by HJF, even though adding this recurrence to the control arm would significantly lower the

p-value and improve the evidence of efficacy of GLSI-100.

As a result of detailed due diligence, we became aware in Q4 of 2023 of a potential

recurrence in the HER2 positive treated arm.

This patient was not reported as a recurrence in the database, on a CRF that should be used

for a recurrence, in reports from the lead clinicians to the FDA, or in the 3 or 4 year follow-up data published by the lead clinicians.

Some CRFs report a recurrence, but the critical CRF that confirms a recurrence was not completed or entered into the database provided

We have since initiated an effort to confirm with HJF and the clinicians who treated this patient the status of this patient,

and if the final CRFs and database should be modified.

It appears that this patient, who had completed treatment with GLSI-100, experienced

a local recurrence that responded well to additional treatment and survived without additional evidence of disease or distant metastasis

for the duration of study follow-up.

Any discrepancies noted to date in the review of the censoring date recorded in the database do

not materially change the study results and the median duration of follow-up remains 5 years.

a recurrence in the control arm would decrease the p-value and still result in a 100% reduction in the recurrence rate, a recurrence

in the treated arm would increase the p-value and would result in an 80% reduction in the recurrence rate.

In either case, we believe

that the reduction in recurrence rate is clinically meaningful and substantial compared to the approximately 20-50% reduction in recurrences

of all other approved breast cancer drugs for this patient population.

These findings have not materially affected the power of the Phase

III study as the assumptions for that design were selected conservatively.

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

trial of HLA-A*02 breast cancer patients, GLSI-100 treatment resulted in no recurrences in 46 HER2/ neu 3+ over-expressor patients

versus 50 placebo patients who were treated with GM-CSF.

After 5 years of follow-up, there were 0% cancer recurrences in the HER2/ neu

3+ patients treated with GLSI-100 versus an 11% cancer recurrence rate in the placebo arm treated with GM-CSF (p = 0.0338) in the

population that was treated, followed, and remained disease free over the first 6 months, which we believe is the time required to reach

peak immunity and thus maximum efficacy and protection.

Based on this data, we believe that treatment with GLSI-100 starting approximately

in the second year following surgery may dramatically lower breast cancer recurrences in this patient population.

trial of HLA-A*02 breast cancer patients, 46 HER2/ neu 3+ over-expressor patients were treated with GLSI-100 and 50 placebo patients

were treated with GM-CSF alone.

After 5 years of follow-up, there was a substantial reduction in cancer recurrences in the HER2/ neu

3+ patients who were treated with GLSI-100, 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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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.

population was treated with GLSI-100 following the first year of trastuzumab treatment, which followed surgery.

In the 96 HER2/ neu 3+, HLA-A*02 patients, a substantial reduction in recurrences was observed

in the efficacy population.

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.

patient population was treated with GLSI-100 following the first year of trastuzumab treatment, which followed surgery.

1-2+ Low to Intermediate Expressors:

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

trastzumab based therapy and other synergistic agents.

trastuzumab based therapy and other synergistic agents.

Year Data Set of GP2 Phase IIb Trial:

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

This time series highlights that

the 10 GLSI-100 immunotherapy injections over the first 2.5 years (as depicted by the 10 arrows on the x-axis) demonstrated a potent

immune response that typically peaked at 6 months.

The immune response also included injection site and systemic reactions that peaked

at approximately 6 months.

We believe that these AEs are a positive sign that the immune system responded to GLSI-100 immunotherapy and

contributed to the decline in metastatic breast cancer recurrence.

The observed AEs associated with GLSI-100 injections were temporary

and declined after GLSI-100 injections ended.

The Kaplan Meier curve and p

value, which are based on recurrence rates or disease free survival and censoring data, is subject to change pending the completion of

the Phase II Clinical Trial Study Report described above.

This time series highlights that the 10 GLSI-100 immunotherapy injections over

the first 2.5 years (as depicted by the 10 arrows on the x-axis) demonstrated a potent immune response that typically peaked at 6 months.

The immune response also included injection site and systemic reactions that peaked at approximately 6 months.

We believe that these

AEs are a positive sign that the immune system responded to GLSI-100 immunotherapy and contributed to the decline in metastatic breast

cancer recurrence.

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

& Immune Response Data of GP2 Phase II Trial

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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.

immunotherapy demonstrated GP2-specific immune responses, which we believe supports 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.

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.

III Trial, Flamingo-01

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population and to pursue additional HER2/ neu -expressing cancers.

Pending the receipt of sufficient capital, the Phase

III clinical trial can be supplemented with 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.

Pending the receipt of sufficient capital, the Phase III clinical

trial can be supplemented with 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

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Capital Management

of March 15, 2023 we had 3 full-time employees and 3 part-time employees.

of April 10, 2024 we had 3 full-time employees and 4 part-time employees.

We are not a party to any collective bargaining agreements.

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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