The following discussion and analysis contains forward-looking statements within
the meaning of the federal securities laws. The safe harbor provided in section
27A of the Securities Act of 1933 and section 21E of the Securities Exchange Act
of 1934 ("statutory safe harbors") shall apply to forward-looking information
provided pursuant to the statements made in this filing by the Company. We urge
you to carefully review our description and examples of forward-looking
statements included in the section entitled "Cautionary Note Regarding
Forward-Looking Statements" at the beginning of this report. Forward-looking
statements speak only as of the date of this report and we undertake no
obligation to publicly update any forward-looking statements to reflect new
information, events or circumstances after the date of this report. Actual
events or results may differ materially from such statements. In evaluating such
statements, we urge you to specifically consider various factors identified in
this report, any of which could cause actual results to differ materially from
those indicated by such forward-looking statements. The following discussion and
analysis should be read in conjunction with the accompanying financial
statements and related notes, as well as the Financial Statements and related
notes in our Annual Report on Form 10-K for the fiscal year ended December 31,
2021 and the risk factors discussed therein.
General
Our principal executive office is located at 701 Wild Rose Lane, Elk City,
Idaho, 83525, our telephone number is (760) 295-7208 and our website is
www.therapeuticsolutionsint.com. The reference to our website does not
constitute incorporation by reference of the information contained on our
website.
We file our quarterly and annual reports with the Securities and Exchange
Commission (SEC), which the public may view and copy at the SEC's Public
Reference Room at 100 F Street, N.E. Washington D.C. 20549, on official business
days during the hours of 10 a.m. to 3 p.m. The public may obtain information on
the operation of the SEC's Public Reference Room by calling the SEC at
1-800-SEC-0330. The SEC also maintains an Internet site, the address of which is
www.sec.gov, which contains reports, proxy and information statements, and other
information regarding issuers which file electronically with the SEC. The
periodic and current reports that we file with the SEC can also be obtained from
us free of charge by directing a request to Therapeutic Solutions International,
Inc., 4093 Oceanside Blvd, Suite B, Oceanside, California 92056, Attn: Corporate
Secretary.
DESCRIPTION OF BUSINESS
CURRENT BUSINESS DESCRIPTION
Therapeutic Solutions International, Inc. ("TSOI" or the "Company") was
organized August 6, 2007 under the name Friendly Auto Dealers, Inc., under the
laws of the State of Nevada. In the first quarter of 2011 the Company changed
its name from Friendly Auto Dealers, Inc. to Therapeutic Solutions
International, Inc., and acquired Splint Decisions, Inc., a California
corporation.
On December 17, 2020, Therapeutic Solutions International, Inc. Board of
Directors made a decision to move our corporate headquarters to Elk City, Idaho
83525 and has purchased real property at 701 Wild Rose Lane and 50 Bullock Lane,
Elk City Idaho 83525. The Company will continue to maintain a satellite office
at the current address of 4093 Oceanside Blvd., Suite B, Oceanside CA, 92056.
4
Business Description
Currently the Company is focused on immune modulation for the treatment of
several specific diseases. Immune modulation refers to the ability to upregulate
(make more active) or downregulate (make less active) one's immune system.
Activating one's immune system is now an accepted method to treat certain
cancers, reduce recovery time from viral or bacterial infections and to prevent
illness. Additionally, inhibiting one's immune system is vital for reducing
inflammation, autoimmune disorders and allergic reactions.
TSOI is developing a range of immune-modulatory agents to target certain
cancers, schizophrenia, suicidal ideation, traumatic brain injury, and for daily
health.
Nutraceutical Division - TSOI has been producing high quality nutraceuticals.
Its current flagship product, QuadraMune®, is a multi-patented synergistic blend
of pterostilbene, sulforaphane, epigallocatechingallate, and thymoquinone.
QuadraMune has been shown to increase Natural Killer Cell activity and healthy
Cytokine production. Our synergistic blend of ingredients help the immune system
fight off common and complex ailments and promote healthy T Cell activity.
Recently the Company was approved to sell certain nutraceuticals on the Amazon
Platform.
Cellular Division - TSOI obtained exclusive rights to a patented adult stem cell
for development of therapeutics in the area of chronic traumatic encephalopathy
(CTE) and traumatic brain injury (TBI) and Lung Pathology (LP).
The stem cell licensed, termed "JadiCell" is unique in that it possesses
features of mesenchymal stem cells, however, outperforms these cells in terms of
a) enhanced growth factor production; b) augmented ability to secrete exosomes;
and c) superior angiogenic and neurogenic ability.
Chronic Traumatic Encephalopathy (CTE) is caused by repetitive
concussive/sub-concussive hits to the head sustained over a period of years and
is often found in football players. The condition is characterized by memory
loss, impulsive/erratic behavior, impaired judgment, aggression, depression, and
dementia. In many patients with CTE, it is anatomically characterized by brain
atrophy, reduced mass of frontal and temporal cortices, and medial temporal
lobe. TSOI has previously filed several patents in the area of CTE based on
modulating the brain microenvironment to enhance receptivity of regenerative
cells such as stem cells. On March 4, 2021 the Company received an IND Serial #
27377 for a clinical trial of 10 patients with CTE.
On August 4th, 2021, the Company announced clearance from the Food and Drug
Administration (FDA) to initiate a Phase III pivotal trial for registration of
the Company's JadiCell™ universal donor stem cell as a treatment for COVID-19
associated lung failure under IND # 19757. In previous studies the Company has
demonstrated the superior activity of JadiCell to other types of stem cells
including bone marrow, adipose, cord blood, and placenta. Furthermore, the
JadiCell was shown to be 100% effective in saving the lives of COVID-19 patients
under the age of 85 in a double-blind placebo controlled clinical trial with
patients in the ICU on a ventilator. In patients over the age of 85 the survival
rate was 91%. The Company also recently announced the launching of Phase III for
IND # 19757 with Biorasi LLC, a global, full-service CRO, who will run the
clinical trial.
In addition, the Company has filed data with the FDA, as part of IND #17448,
which demonstrated that treatment of cancer patients with StemVacs™ resulted in
enhanced activity of a type of immunological cell called "natural killer" cells,
otherwise known as "NK cells."
The Company has also developed an allogenic version of StemVacs and has filed
patents to cover activating universal donor immune system cells called dendritic
cells in a manner so that upon injection they reprogram the body's NK cells.
Most recently the Company announced filing of a patent application covering the
use of JadiCells™ for treatment of epilepsy and associated conditions.
5
Investigational Drug Applications:
Treatment of Metastatic Breast Cancer by StemVacs-V Cancer Immunotherapeutic IND
#
The Primary Objective is safety and feasibility of StemVacs-V administration at
12 months as assessed by lack of adverse medical events. The Secondary Objective
is efficacy as judged by tumor response, time to progression, and immunological
monitoring.
Safety, Feasibility, and Immunomodulatory Activities of StemVacs in Patients
with Advanced Solid Tumors IND # 17448
The Primary Objective is safety and feasibility of StemVacs administration at 12
months as assessed by lack of adverse medical events. The Secondary Objective is
efficacy as judged by tumor response, time to progression, and immunological
monitoring.
Umbilical Cord-derived Mesenchymal Stem Cells for Patients with COVID-19
("UC-MSC for COVID-19") IND # 19757
The primary objective will be to assess effectiveness of UC-MSC treatment on
proportion of patients alive and free of respiratory failure at Day 60 after
randomization. The secondary objectives will be to assess all-cause mortality at
Day 60, survival at day 31, number of subjects experiencing serious adverse
events (SAEs) by day 31, SAE-free survival, time to recovery (evaluated until
day 60), and time to oxygen requirement equal or below 40% oxygen.
Investigation of Umbilical Cord-derived Mesenchymal Stem Cells for the Treatment
of Chronic Traumatic Encephalopathy Patients IND # 27377
To determine safety and efficacy of 100 million intravenously administered
JadiCell™ allogeneic umbilical cord mesenchymal stem cells. Efficacy will be
determined by behavioral scores, brain imaging, and reduction in inflammatory
markers. Toxicity of treatment was evaluated for the duration of the study and
will be graded according to the criteria of the World Health Organization.
JadiCell Therapy for COPD IND # 28508
To determine safety and efficacy of intravenously administered allogeneic
JadiCell umbilical cord blood mesenchymal stem cells in patients with
moderate-to-severe COPD. The Primary Endpoint, which is toxicity, will be
assessed by number of adverse events (AEs). The Secondary Endpoint, which is
efficacy will be evaluated at baseline and days 30, 60, and 90.
Nutraceutical Division (TSOI)
? ProJuvenol® is a patented, (US No.: 9,682,047) and powerful synergistic blend
of complex anti-aging ingredients in capsules.
? NanoStilbene™ is an easily absorbed nanoemulsion of nanoparticle pterostilbene
derived from the '047 patent.
? DermalStilbene is a topical form of pterostilbene delivered via spray
application onto skin, derived from the '047 patent.
? IsoStilbene an injectable formulation of pterostilbene is available by
prescription only, derived from the '047 patent.
? NeuroStilbene is an intranasal form of pterostilbene delivered via spray
application inside the nostril, derived from the '047 patent.
? NanoPlus is a blend of NanoStilbene and Nano Cannabidiol which are an easily
absorbed Nanoparticles formulation of Pterostilbene and Cannabidiol.
? Nano Cannabidiol is an easily absorbed Nanoparticle formulation of Cannabidiol
Isolate in the range of 75-90 nanometers. This product is built on the same
nano platform as NanoStilbene and is delivered at a concentration of 200mg per
milliliter.
6
? NanoPSA is a blend of NanoStilbene™ and Broccoli Sprout Extract (BSE)
providing 74mg of BSE and 125mg of our patented NanoStilbene, a proprietary
formulation of nanoparticle pterostilbene.
? NLRP3 Trifecta is a two-product combo and consists of one bottle of NanoPSA
and one bottle of GTE-50 green tea extract.
? QuadraMune™ is a multi-patented synergistic blend of pterostilbene,
sulforaphane, epigallocatechingallate, and thymoquinone.
? NuBrainer™ HSCP is a nootropic blend of Huperzine-A, Sterubin, Cannabidiol,
and Pterostilbene.
Patents:
On November 14, 2022, the Company filed a patent titled "Treatment of Chronic
Obstructive Pulmonary Disease with Myeloid Derived Suppressor Cells" which
discloses compositions of matter, protocols, and treatment means for prevention
and/or reversing Chronic Obstructive Pulmonary Disease (COPD) using myeloid
derived suppressor cells as a monotherapy or adjuvant therapy. In one
embodiment umbilical cord low density myeloid cells are expanded using
interleukin-3 and GM-CSF and administered in an allogeneic manner to a mammal
suffering from COPD. In some embodiments combinations of myeloid derived
suppressor cells and mesenchymal stem cells are disclosed.
On October 24, 2022, the Company filed a patent application titled "Mesenchymal
Stem Cell Therapy of Epilepsy and Seizure Disorders" which discloses novel
compositions of matter and treatment methods for reducing and/or reversing
epilepsy through administration of mesenchymal stem cells in order to induce
immune modulation and/or regenerative processes. In one embodiment umbilical
cord mesenchymal stem cells are administered to a patient suffering from
epilepsy at a concentration and frequency sufficient to inhibit neuronal
hyperactivation and/or reduce neuroinflammatory status of the patient.
On October 03, 2022, the Company filed a patent application titled "Stimulation
of Pulmonary Regenerative Exosomes by Mesenchymal Stem Cells and Derivatives
Thereof" which discloses therapeutic means for pulmonary degenerative conditions
through the administration of mesenchymal stem cells in order to induce
regenerative exosomes from dendritic cells expressing CD103. In one embodiment
cultures of mesenchymal stem cells with dendritic cell progenitors are disclosed
wherein said mesenchymal stem cells induce a modulation of STAT3 signaling in
said dendritic cell endowing a regenerative property to said dendritic cells and
exosomes derived from said cells.
On September 19, 2022, the Company filed a patent application titled "Treatment
of Bipolar Disorder Using Mesenchymal Stem Cells and Modification of Mesenchymal
Stem Cells" that discloses the utilization of mesenchymal stem cells, exosomes
from mesenchymal stem cells, conditioned media from mesenchymal stem cells,
apoptotic bodies from mesenchymal stem cells, and modified mesenchymal stem
cells for treatment of bipolar disorder. In one embodiment mesenchymal stem
cells isolated from umbilical cord tissue are treated with carbon monoxide at a
concentration sufficient to induce activation of heme-oxygenase I and infused
into a patient at risk or suffering from bipolar disorder.
On September 12, 2022, the Company filed a patent application titled "Treatment
of COPD by Stimulation of Stem Cell Mobilization" which discloses means of
inducing pulmonary regeneration and/or protection from oxidative stress by
stimulation of endogenous stem cell mobilization together with one or more
inhibitors of NF-kappa B and/or one or more inhibitors of oxidative stress. The
invention discloses the unexpected finding that G-CSF administration enhances
oxidative stress and pulmonary damage, however, coadministration with
pterostilbene, results in synergistic suppression of COPD pathology.
On August 29, 2022, the Company filed a patent application titled "Gene
Silencing Therapy of Acute Respiratory Disorder" that teaches treatment means,
compositions of matter and protocols useful for suppression of acute respiratory
disorder (ARDS) through induction of RNA interference in the pulmonary
microenvironment alone and/or in conjunction with mucolytic and/or DNA
disrupting agents. In one embodiment short interfering RNA (siRNA) is prepared
which targets complement receptors C3R and/or C5R together with TNF-receptor,
IL-6 receptor and/or TLR4 and TLR9. In some embodiments NanoStilbene is utilized
as a delivery vehicle for siRNA delivery.
On August 12, 2022, the Company filed a patent application titled "Treatment of
Chronic Obstructive Pulmonary Disease by Mesenchymal Stem Cell Apoptotic Bodies
and Compositions Thereof" that discloses means, treatments and compositions of
matter useful for treatment of chronic obstructive pulmonary disease (COPD). In
one embodiment the invention provides the administration of mesenchymal stem
cell apoptotic bodies alone or in combination with "regenerative adjuvants" to
prevent and/or reverse reduction in lung function associated with COPD. In other
embodiments the invention teaches the utilization of stem cell apoptotic bodies
for induction of pulmonary regeneration directly or indirectly.
On July 29, 2022, the Company filed a patent application titled "Gene Modified
iPSC Derived Cellular Compositions for Regeneration and Immune Modulation" that
disclosed cells and cellular compositions useful for treatment of degenerative
and/or autoimmune diseases derived from gene edited/gene modified pluripotent
stem cells. In one embodiment pluripotent stem cell such as inducible
pluripotent stem cells are gene modified to express tissue associated
transcription factors such as pdx-1 if endodermal tissue is desired and cells
are differentiated into regenerative-type cells such as along the mesenchymal
lineage. In one embodiment the invention teaches transfection with IL-27 to
induce expression of coinhibitory molecules for suppression of autoimmunity. In
some embodiments the invention provides generation of iPSC derived MSC which
cannot stimulate inflammation due to gene-editing based removal of inflammatory
associated transcription factors.
7
On May 12, 2022, the Company filed a patent application titled "Inhibition and
Reversion of Chronic Obstructive Pulmonary Disease (COPD) by Endothelial Cell
Regeneration" that teaches means, treatment methods, and compositions of matter
useful for prevention and/or reversion of chronic obstructive pulmonary disease
(COPD). In one embodiment the invention provides the administration of
mesenchymal stem cells and exosome thereof as a means of augmenting endogenous
endothelial regeneration and/or endothelial regeneration stimulated by exogenous
means. In some embodiments the invention provides administration of allogeneic
mesenchymal stem cells together with autologous endothelial progenitor cells
and/or mobilization of said autologous endothelial progenitor cells.
On March 7, 2022, the Company filed a patent application titled "Treatment of
Trauma Associated Cognitive Dysfunction Using Mesenchymal Stem Cell Apoptotic
Bodies and Compositions Thereof" which teaches means, treatments and
compositions of matter useful for treatment of chemotherapy/radiotherapy
associated cognitive dysfunction. In one embodiment the invention provides the
administration of mesenchymal stem cell apoptotic bodies alone or in combination
with "regenerative adjuvants" to prevent and/or reverse cognitive dysfunction
associated with chemotherapy and/or radiation therapy. In other embodiments the
invention teaches the utilization of stem cell apoptotic bodies for induction of
neuroregeneration directly or indirectly.
On February 7, 2022, the Company filed a patent application titled "Treatment of
COVID-19 Associated Cognitive Dysfunction by Nutraceutical Preparations" that
teaches means and methods of treating cognitive dysfunction associated with
COVID-19 and/or other associated with inflammatory conditions. In one embodiment
treatment of COVID-19 cognitive dysfunction performed by administration of
nutraceutical means, wherein said nutraceuticals are administered at a frequency
and/or concentration sufficient to induce proliferation of endogenous neural
progenitor cells and/or protect cells from inflammatory damage. In one
embodiment said nutraceuticals are comprised of green tea extract, and/or
nigella sativa, and/or pterostilbene, and/or sulforaphane. In some embodiments
nutraceutical compositions are utilized to overcome treatment resistant of
currently used antidepressants.
On November 1, 2021, the Company filed a patent application titled "Induction of
Concurrent Pulmonary Immune Modulation and Regeneration by Protein Mediated
Conjugation of Immune Regulatory Cells with Endogenous Progenitor Cells" that
discloses means, methods and compositions of matter useful for treatment of
inflammatory pulmonary diseases such as COVID-19 through administration of
agents that facilitate interaction between immune modulatory cells and
endogenous pulmonary progenitor cells. In one embodiment a bispecific antibody
capable of facilitating the interaction between CD25 on T regulatory cells and
CD47 on pulmonary epithelial stem cells is described.
On October 11, 2021, the Company filed a patent application titled "Umbilical
Cord Derived Regenerative and Immune Modulatory Stem Cell Populations" which
provides universal donor cellular populations derived from umbilical cords
possessing ability to elicit immune modulation and evoke regeneration when
administered into a mammalian host. Generation of cellular products for clinical
use are provided including methodologies of expansion, characterization, and
means of therapeutic implementation.
On October 4, 2021, the Company filed a patent application titled "Reduction of
Neutrophil Extracellular Trap formation by Mesenchymal Stem Cells and their
Exosomes" that disclosed methods of reducing lung inflammation in acute
respiratory distress syndrome elicited by various factors such as COVID-19
infection by reduction of neutrophil extracellular trap formation through
administration of mesenchymal stem cells and/or exosomes thereof. The invention
provides means of inhibiting neutrophil release of extracellular traps by
mesenchymal stem cells and/or exosomes derived from said mesenchymal stem cells.
Additionally, synergies are provided between mesenchymal stem cells and/or
exosomes derived from mesenchymal stem cells and agents approaches which reduce
neutrophil extracellular trap formation.
On September 22, 2021, the Company filed a patent application titled
"Stimulation of Mesenchymal Stem Cell Therapeutic Activities by T Regulatory
Cells" teaches novel means of enhancing mesenchymal stem cell regenerative
activities including, intra alia, production from pulmonary leakage and
suppression of scar tissue formation by co-administration with T regulatory
cells. In some embodiments the invention provides an interaction between T
regulatory cells and mesenchymal stem cells in which T regulatory cells
stimulate upregulation of mesenchymal stem cell activity in a GITR dependent
manner.
On September 16, 2021, the Company filed a patent application titled "Ivermectin
Compositions for Treatment of COVID-19" that discloses novel mechanisms of
action of ivermectin therapy as related to treatment of COVID-19 and means of
augmenting therapeutic activities by co-administration with one or more of the
following: pterostilbene, thymoquinone, epigallocatechin-3-gallate, and
sulforaphane. In one embodiment the invention provides enhanced reduction of
inflammation induced pulmonary leakage without augmenting immune suppressive
mechanisms.
On August 23, 2021, the Company filed a patent application titled "Umbilical
Cord Mesenchymal Stem Cells for Treatment of Chronic Obstructive Pulmonary
Disease and Lung Degeneration" that discloses means of treating lung
degenerative diseases including chronic obstructive pulmonary disease (CODP)
using umbilical cord mesenchymal stem cells such as JadiCells alone, and/or
using said cells under conditions that are activated in order to endow enhanced
regenerative activity. In one embodiment said activation of said mesenchymal
stem cells is performed through stimulation with a toll like receptor agonist at
a concentration and duration sufficient to induce a >50% increase in
keratinocyte growth factor expression from said stem cells. In another
embodiment the invention provides the use of JadiCells as a means of producing
exosomes, wherein said exosomes possess therapeutic properties capable of
reducing inflammation, fibrosis and degeneration associated with COPD, as well
as stimulation of regenerative activity. In some JadiCells are activated by a
treatment with Activated Protein C.
8
On August 18, 2021, the Company filed a patent application titled "Enhancement
of Umbilical Cord Mesenchymal Stem Cell Therapeutic Activity by Stimulators of T
Regulatory Cells and/or Cells Expressing CD73" that teaches compositions of
matter and protocols useful for treatment of COVID-19 and/or other inflammatory
pathologies through stimulation of T regulatory cells and/or T cells expressing
CD73 using administration of umbilical cord derived mesenchymal stem cells such
as JadiCells. In one embodiment dosage of JadiCells needed to treat a patient is
determined by the increase of T regulatory cells and/or CD73 expressing cells
that are increased in number and/or activity subsequent to a test dose of
JadiCells. In another embodiment stimulators of T regulatory cells and/or CD73
expressing T cells are utilized together with JadiCells in order to augment
therapeutic activity. In some embodiments administration of JadiCell is
performed with low dose interleukin-2 as a treatment for COVID-19 or other
inflammatory related pathologies.
On August 11, 2021, the Company filed a patent application titled "Induction of
Neurogenesis using Umbilical Cord Derived Mesenchymal Stem Cells and Derivatives
Thereof" that disclosed compositions of matter and protocols useful for
treatment of neurological dysfunctions through stimulation of adult neurogenesis
using administration of umbilical cord derived mesenchymal stem cells such as
JadiCells. In one embodiment viral induced neuropathy is reduced by
administration of JadiCells to stimulate neurogenesis. In another embodiment the
neurogenic activity of selective serotonin reuptake inhibitors is enhanced by
administration of JadiCells. In some embodiments administration of JadiCell
exosomes, conditioned media, microvesicles and/or apoptotic bodies is utilized
to stimulate neurogenesis.
On July 6, 2021, the Company filed a patent application titled "Treatment of
Parkinson's Disease by Immune Modulation and Regenerative Means" in which we
describe and disclose means, methods and compositions of matter for treatment
Parkinson's Disease through concurrent immune modulation and regenerative means.
In one embodiment Parkinson's Disease is treated by augmentation of T regulatory
cell numbers and/or activity while concurrently providing regenerative cells
such as mesenchymal stem cells, and/or dopamine secreting cells. In one
embodiment administration of immunoglobulins such as IVIG together with low dose
interleukin-2 and/or low dose naltrexone is disclosed as a preparatory means
prior to administration of therapeutic cells such as stem cells. Other
therapeutic means utilized in an adjuvant manner are also provided for hormonal
rebalancing, transcranial magnetic stimulation, and deep brain stimulation.
On May 24, 2021, the Company filed a patent application titled "Immunotherapies
for Targeting of Tumor Vasculature" that disclosed novel means, protocols, and
compositions of matter for creating targeted immune responses and/or induction
of immunological memory towards the tumor vasculature. In one embodiment
pluripotent stem cells are transfected with one or more genes capable of
eliciting immunity, induced to differentiate into endothelial-like cells which
resemble the tumor endothelial cells, and utilized as a vaccine. In some
embodiment's genes are engineered under control of specific promoters to allow
for various specificities of activity. In one specific embodiment pluripotent
stem cells engineered to endow properties capable of inducing expression of the
?- Gal epitope (Gal?1,3Gal?1,4GlcNAc-R). Addition of adjuvants to enhance
antigen presentation of the vaccine composition, as well as means of stimulating
systemic enhancement of circulating endothelial specific T cells are also
disclosed.
On May 21, 2021, the Company filed a patent application titled "Lithium as a
Monotherapy and/or Stem Cell Adjuvant Therapy for Pulmonary Fibrosis" that
disclosed compositions of matter, therapeutics, and protocols useful for
reduction and/or reversion of pulmonary fibrosis. In one specific embodiment
lithium chloride is administered together with a regenerative cell in a patient
suffering from, or at risk of pulmonary fibrosis. In one embodiment said lithium
chloride is administered as an adjuvant to a regenerative therapy, wherein said
regenerative therapy is a gene therapy, a protein therapy, a cell therapy, or a
tissue transplant. In one embodiment lithium chloride, or a salt thereof is
utilized alone, or with a regenerative means, to evoke preservation and/or
elongation of telomere length in pulmonary tissue. In one embodiment the
invention teaches administration of umbilical cord mesenchymal stem cells (MSC)
and/or products derived from said cells in order to induce an inhibition of
natural or pathological reduction of telomere length, to preserve telomere
length or to enhance telomere length. In one embodiment the MSC described in the
invention as useful are umbilical cord derived MSC.
On May 17, 2021, the Company filed a patent application titled "Treatment of
Major Depressive Disorder by Low Dose Interleukin-2" which teaches methods,
compositions of matter, and protocols useful for treatment of major depressive
disorder through administration of low dose interleukin- 2 at a concentration
and/or frequency sufficient to increase expansion of T regulatory cell numbers
and/or enhancement of T regulatory cell activity. In some embodiments
administration of interleukin-2 is provided as means of enhancing efficacy of
standard antidepressant therapies. Furthermore, administration of interleukin-2
receptor agonists is also described in the current invention as a treatment of
major depressive disorder.
On April 13, 2021, the Company filed a patent application titled "Amelioration
and Treatment of Opioid Addiction" that discloses compositions of matter,
protocols and treatment means for reducing and/or preventing opioid addiction.
In one embodiment the invention teaches intranasal administration of umbilical
cord blood plasma, or extracts thereof, together with pterostilbene or
pterostilbene containing nanoparticles, and/or oxytocin, and/or human chorionic
gonadotropin.
9
On March 29, 2021, the Company filed a patent application titled "Compositions
Capable of Stimulating Immunity Towards Tumor Blood Vessels" which discloses
novel means, protocols, and compositions of matter for eliciting an immune
response against blood vessels supplying neoplastic tissue. In one embodiment
pluripotent stem cells are transfected with one or more genes capable of
eliciting immunity. In some embodiments such genes are engineered under control
of specific promoters to allow for various specificities of activity. In one
specific embodiment pluripotent stem cells engineered to endow properties
capable of inducing expression of the ?-Gal epitope (Gal?1,3Gal?1,4GlcNAc-R).
On March 23, 2021, the Company filed a patent application titled "Chimeric Cells
Comprising Dendritic Cells and Endothelial Cells Resembling Tumor Endothelium"
which disclosed are means, methods and compositions of matter useful for
induction of immunological responses towards tumor endothelial cells. In one
embodiment the invention teaches fusion of dendritic cells and cells resembling
tumor endothelial cells and administration of such chimeric cells as an
immunotherapy for stimulation of tumor endothelial cell destruction. In other
embodiments pluripotent stem cells are utilized to generate dendritic cells,
wherein said dendritic cells are fused with pluripotent stem cell derived
endothelial cells created in a manner to resemble tumor endothelial cells.
On March 16, 2021, the Company filed a patent application titled "Pluripotent
Stem Cell Derived Dendritic Cells and Engineered Dendritic Cells for Cancer
Immunotherapy" which disclosed are populations of dendritic cells generated from
stem cells capable of inducing immunity towards cancer. In one embodiment said
dendritic cells are generated from allogeneic inducible pluripotent stem cells,
for some uses, said pluripotent stem cells are genetically engineered/edited to
induce cancer specific immunity and/or resist immunosuppressive effect of tumor
derived microenvironment. In one embodiment pluripotent stem cells are
transfected with cancer stem cell antigens such as BORIS and/or NR2F6.
On March 4, 2021, the Company filed a patent application titled "Therapeutic
Monocytes for Prevention of Suicidal Ideation" that discloses compositions of
matter, protocols, and therapeutic means for treatment of suicidal ideations
and/or suppression of suicidal attempts. In one embodiment the invention
provides the use of umbilical cord derived monocytes as a means of treatment. In
another embodiment, monocytes are de-differentiated from adult monocytes using
reprogramming means to create monocyte capable of producing anti-inflammatory as
well as regenerative properties useful in reducing suicidal ideations and/or
attempts. Published on September 8, 2022,
https://patents.justia.com/patent/20220280574
On February 2, 2021, the Company filed a patent application titled "Ex Vivo
Generation of Immunocytes Recognizing Brother Of The Regulator of Imprinted
Sites (BORIS) Expressing Cancer Stem Cells" that discusses means, methods and
compositions of matter useful for induction of immunity towards cancer stem
cells by providing a dendritic cell, wherein said dendritic cells express BORIS
and/or peptides derived from BORIS, wherein said dendritic cell is cultured in
the presence of one or more immunocytes. In one embodiment said dendritic cells
are derived from umbilical cord blood sources and allogeneic to T cells, which
are expanded ex vivo and used for the purposes of immunotherapy.
Published on August 25, 2022, https://patents.justia.com/patent/20220267730
On February 8, 2021, the Company filed a patent application titled "Stimulation
of Natural Kill Cell Memory by Administration of Dendritic Cells" which
disclosed means, methods and compositions of matter useful for induction of
natural killer cell memory by administration of dendritic cells and/or exosomes
thereof. In one embodiment a mammal suffering from cancer is administered
allogeneic cord blood derived dendritic cells that are not pulsed exogenously.
In one embodiment the dendritic cells are stimulated to possess chemotactic
activity towards the tumor by culture of dendritic cell progenitors in hypoxia.
Natural killer cell memory is induced, in part, by triggering of upregulation of
cytokines associated with homeostatic expansion such as interleukin 7 and
interleukin 15.
Published on August 11, 2022, https://patents.justia.com/patent/20220249551
On January 26, 2021, the Company filed a patent application titled "Stimulation
of Dendritic Cell Activity by Homotaurine and Analogues Thereof" which discloses
means, methods, and compositions of matter useful for enhancement of dendritic
cell activity. In one embodiment the invention provides the use of GABA agonists
such as homotaurine for stimulation of dendritic cell activity. In one
embodiment said dendritic cell activity is enhancement of natural killer cell
activity and/or of T cell activity. In one embodiment NK cell activity is
ability to induce cytotoxicity in neoplastically transformed cells, whereas T
cell activity is either cytokine production for CD4 cells or cytotoxicity for
CD8 cells.
Published on July 28, 2022, https://patents.justia.com/patent/20220235325
On December 21, 2020, the Company filed a patent application titled
"Immunotherapy for Opioid Addiction" which teaches means, methods and
compositions of matter useful for reduction of brain inflammation and prevention
of opioid addiction and/or tolerance. In one embodiment the invention provides
utilization of platelet rich plasma (PRP), alone, or admixed with
regenerative/anti-inflammatory adjuvants, for reduction of neural inflammation.
In one embodiments PRP is admixed with oxytocin and administered intranasally in
a patient at risk of opioid addiction. In another embodiment, PRP is admixed
with fortified and non-fortified nigella sativa oil, and/or pterostilbene and
administered intranasally. Other embodiments include utilization of autologous
stromal vascular fraction cells alone and/or admixed with
regenerative/anti-inflammatory adjuvants.
Published on June 23, 2022, https://patents.justia.com/patent/20220193127
10
On December 8, 2020, the Company filed a patent application titled "Treatment of
Major Depressive Disorder and Suicidal Ideations Through Stimulation of
Hippocampal Neurogenesis Utilizing Plant-Based Approaches" that teaches means
and methods of treating major depressive disorder and/or other disorders that
predispose to suicide by administration of nutraceutical means, wherein said
nutraceuticals are administered at a frequency and/or concentration sufficient
to induce proliferation of endogenous neural progenitor cells. In one embodiment
said nutraceuticals are comprised of green tea extract, and/or nigella sativa,
and/or pterostilbene, and/or sulforaphane. In some embodiment's nutraceutical
compositions are utilized to overcome treatment resistant of currently used
antidepressants. Published on June 9, 2022,
https://patents.justia.com/patent/20220175701
On November 24, 2020, the Company filed a patent application titled "Stimulation
of NK Cell Activity by QuadraMune Alone and together with Metformin" that
disclosed means, compounds, and compositions of matter useful for stimulation of
natural killer cell activity. In some embodiments the invention teaches the
administration of a therapeutic combination of ingredients comprising of
metformin, pterostilbene, nigella sativa, sulforaphane, and
epigallocatechin-3-gallate (EGCG) to a mammal in need of natural killer cell
immune modulation. In another embodiment, the invention teaches administration
of said therapeutic combination to a mammal infected with said SARS-CoV-2. In
some embodiments dosage of said therapeutic combination is based on inflammatory
and/or immunological parameters observed in patients with COVID-19.
Published on May 26, 2022, https://patents.justia.com/patent/20220160809
On October 27, 2020, the Company filed a patent application titled
"Protection/Regeneration of Neurological Function by Endothelial
Protection/Rejuvenation" using Stem Cells for Treatment of Conditions such as
Chronic Traumatic Encephalopathy and Schizophrenia" which therapeutic compounds,
protocols, and compositions of matter useful for treatment of neurological
conditions. In one embodiment the invention teaches the treatment of chronic
traumatic encephalopathy (CTE) through protecting/regenerating the endothelial
by administration of cells such as stem cells. In one embodiment stem cells are
administered in order to protect the endothelium from apoptosis and to preserve
the blood brain barrier. In another embodiment stem cells are administered
together with endothelial progenitor cells in order to regenerate neural
endothelium. In other embodiments preservation of brain integrity in conditions
of degeneration is accomplished by administration of stem cells and/or
endothelial cells. Published on April 28, 2022,
https://patents.justia.com/patent/20220125852
On October 18, 2020, the Company filed a patent application titled
"Nutraceutical Reduction Prevention and/or Reversion of Multiple Sclerosis" that
discloses compositions of matter, protocols, and treatment means for preventing
and/or reversing multiple sclerosis in a mammal. In one embodiment
administration of compositions containing pterostilbene, and/or nigella sativa,
and/or sulforaphane, and/or epigallocatechin-3-gallate (EGCG) are provided.
Published on June 23, 2022, https://patents.justia.com/patent/20220193170
On September 24, 2020, the Company filed a patent application titled
"Personalized Immunotherapies for Reduction of Brain Inflammation and Suicide
Prevention" that discloses means, methods and compositions of matter useful for
reduction of brain inflammation and prevention of suicidal ideations and
suicidal attempts. In one embodiment the invention provides utilization of
autologous platelet rich plasma, alone, or admixed with
regenerative/anti-inflammatory adjuvants, for reduction of neural inflammation.
In one embodiment autologous PRP is admixed with oxytocin and administered
intranasally in a patient at risk of suicidal ideation. In another embodiment,
PRP is admixed with fortified and non-fortified nigella sativa oil and
administered intranasally. Other embodiments include utilization of autologous
stromal vascular fraction cells alone and/or admixed with
regenerative/anti-inflammatory adjuvants. Published on March 24, 2022,
https://patents.justia.com/patent/20220088086
On September 14, 2020, the Company filed a patent application titled
"Immunotherapy of Schizophrenia and Schizophrenia Associated Suicidal
Ideation/Suicide" Disclosed are methods, means, and protocols of modifying the
immune system so as to induce an immunologically tolerant state insofar as T
regulatory cell number and/or activity is augmented in a patient suffering from
schizophrenia. In one embodiment T regulatory cells are administered to the
patient from exogenous sources, be they allogeneic or autologous. In other
embodiments, T regulatory cells are generated endogenously through
administration of immature dendritic cells, mesenchymal stem cells, and/or
pharmaceutical means.
On August 28, 2020, the Company filed a patent application titled "Upregulation
of Therapeutic T Regulatory Cells and Suppression of Suicidal Ideations in
Response to Inflammation by Administration of Nutraceutical Compositions Alone
or Combined with Minocycline" which discloses compositions of matter, treatments
and protocols useful for induction of T regulatory cells in response to
inflammation, as well as inhibition of suicidal ideations and/or
neuroinflammation. In some embodiments the invention teaches the administration
of a therapeutic combination of ingredients comprising of minocycline,
pterostilbene, nigella sativa, sulforaphane, and epigallocatechin-3-gallate
(EGCG) to a mammal undergoing upregulation of inflammatory mediators. Published
on March 3, 2022, https://patents.justia.com/patent/20220062367
On August 21, 2020, the Company filed a patent application titled "Methods of
Determining Risk of Suicide and/or Suicidal Ideation by Immunological
Assessment" which discloses means and methods of identifying risk of suicide
and/or suicidal ideation by assessment of immunologically related cytokines and
cells. In one embodiment, a score, termed the "Campbell Score" is devised based
on assessment of serum cytokines, ability of immune cells to make cytokines when
stimulated ex vivo, and ability of immune cells to produce neurotransmitters
when stimulated ex-vivo. In one embodiment the concentration of interleukin-6 is
utilized as a means of assessing suicidal propensity along, and/or in
combination with metabolites of the enzyme indolamine 2,3 deoxygenase.
11
On August 05, 2020, the Company filed a patent application titled "Prevention of
Neuroinflammation associated Memory Loss Using Nutraceutical Compositions" which
discloses means, methods, and therapeutic compositions for prevention of memory
loss during situations of neuroinflammation. In one embodiment the invention
teaches administration of the therapeutic combination of ingredients comprising
of pterostilbene, Nigella sativa, sulforaphane, and epigallocatechin-3-gallate
(EGCG) to a mammal suffering from inflammation in order to preserver memory
function.
Published on February 10, 2022, https://patents.justia.com/patent/20220040248
On July 28, 2020, the Company filed a patent application titled "Neuroprotection
and Neuroregeneration by Pterostilbene and Compositions Thereof" with new data
demonstrating that the blueberry derived compound pterostilbene possesses
numerous brain protective and potentially brain regenerative activities. The
data disclosed by the Company indicates: a) pterostilbene suppresses
inflammatory cytokines TNF-alpha, IL-1 beta and IL-6; b) pterostilbene inhibits
death of neurons caused by inflammatory mediators; c) pterostilbene stimulates
production of regenerative factors from cells in the brain such as BDNF, NGF,
FGF-1, and FGF-2; and d) pterostilbene allows/enhances proliferation of
endogenous brain stem cells.
Published on February 3, 2022, https://patents.justia.com/patent/20220031793
On July 22, 2020, the Company filed a patent application titled "Additive and/or
Synergistic Combinations of Metformin with Nutraceuticals for the Prevention,
Inhibition and Treatment of SARS-Cov-2 and Associated COVID-19" showing potent
synergy between QuadraMune™ and the antidiabetic drug metformin in treating
COVID-19 associated lung damage models. It was discovered that the ability of
QuadraMune™ to protect the lungs from inflammation that resembles
coronavirus-induced pathology is markedly amplified by concurrent administration
of metformin. At a mechanistic level, it was shown that metformin increased the
ability of QuadraMune™ to a) increase the number of "healing macrophages" ("M2"
macrophages); b) augment production of anti-inflammatory and regenerative
proteins; and c) suppress production of pathological inflammatory proteins.
Published on January 27, 2022, https://patents.justia.com/patent/20220023237
On July 13, 2020, the Company filed a patent application titled "Prevention of
Pathological Coagulation in COVID-19 and other Inflammatory Conditions" s
directed to the utilization of pterostilbene, and/or nigella sativa extract,
and/or sulforaphane, and/or Epigallocatechin gallate (EGCG) alone or in
combination, for the prevention of pathological coagulation. In on embodiment a
composition containing all four ingredients is administered to a patient at risk
of hypercoagulation in order to prevent aberrant expression of pro-coagulation
molecules and/or induce expression of molecules known to suppress coagulation.
In one embodiment the invention teaches administration of pterostilbene,
thymoquinone, sulforaphane, and EGCG as a means of decreasing expression of
tissue factor. Published on May 12, 2022,
https://patents.justia.com/patent/20220143123
On June 30, 2020, the Company filed a patent application titled "Augmentation of
Natural Killer Cell Activity and Induction of Cytotoxic Immunity Using Leukocyte
Lysate Activated Allogeneic Dendritic Cells: StemVacs™" which describes the
process of preparing allogeneic dendritic cells utilizing a leukocyte lysate
based approach. These data support development of StemVacs for conditions that
would benefit from NK activation such as cancer and COVID-19.
Published on March 31, 2022, https://patents.justia.com/patent/20220096542
On June 22, 2020, the Company filed a patent application titled "Treatment of
SARS-CoV-2 with Dendritic Cells for Innate and/or Adaptive Immunity" that
disclosed means, methods, and compositions of matter for prophylaxis and/or
treatment of SARS-CoV-2 by administration of dendritic cells in a manner and
frequency sufficient to induce activation of innate and/or adaptive immune
responses. In one embodiment the invention teaches administration of dendritic
cells pulsed with one or more innate immune stimulants in a manner endowing said
dendritic cell with ability to induce augmentation of natural killer (NK) cell
number and/or activity. In another embodiment the invention teaches the use of
dendritic cells stimulated with innate immune activators in a manner to allow
for uptake of viral particles and presentation of viral epitopes to T cells in
order to stimulate immunological activation and/or memory responses. Published
on December 23, 2021, https://patents.justia.com/patent/20210393681
On June 15, 2020, the Company filed a patent application titled "Nutraceuticals
for Suppressing Indolamine 2,3 Deoxygenase" from new data showing QuadraMune™
significantly inhibited inflammation associated with memory impairment, as well
as reduced levels of kynurenine. Elevation of kynurenine is associated with
activation of indolamine 2,3 deoxygenase, an enzyme associated with inflammation
and depression. Granted on January 25, 2022,
https://patents.justia.com/patent/11229674
On June 11, 2020, the Company filed a patent application titled "Nutraceuticals
for Reducing Myeloid Suppressor Cells" which disclosed compositions of matter,
treatments and protocols useful for reduction of number and/or activity of
myeloid suppressor cells (MSC). In some embodiments the invention teaches the
administration of a therapeutic combination of ingredients comprising of
pterostilbene, Nigella sativa, sulforaphane, and epigallocatechin-3-gallate
(EGCG) to a mammal at possessing an increased number and/or activity of said MSC
in which reduction of number and/or activity is desired. In another embodiment,
the invention teaches administration of said therapeutic combination to a mammal
infected with viral and/or bacterial infections and/or neoplasia. In some
embodiments dosage of said therapeutic combination is based on inflammatory
and/or immunological parameters observed in patients. Published on December 16,
2021, https://patents.justia.com/patent/20210386815
12
On May 11, 2020, the Company filed a patent application titled "Treatment of
COVID-19 Lung Injury Using Umbilical Cord Plasma Based Compositions" which
disclosed means, methods, and compositions of matter useful for the treatment of
lung inflammation associated with viral and bacterial infections, as well as
with systemic inflammation, through the administration of umbilical cord blood
derived plasma-based compositions. In one embodiment the invention teaches
administration of umbilical cord blood plasma together with pterostilbene,
and/or sulforaphane, and/or thymoquinone, and/or Epigallocatechin gallate (EGCG)
and/or n-acetylcysteine in an aerosolized manner to patients suffering from
COVID-19 associated pulmonary deficiencies. In another embodiment, umbilical
cord blood plasma is administered with immune-stimulatory agents in order to
concurrently inhibit propagation of viral load in the lung while suppressing
pulmonary deficiencies.
On May 4, 2020, the Company filed a patent application titled "Nutraceuticals
for the Prevention, Inhibition and Treatment of SARS-Cov-2 and Associated
COVID-19" which teaches compositions of matter, treatments and protocols useful
for prevention of SARS-CoV-2 infection, as well as inhibition of viral
propagation and acceleration of viral cure. In some embodiments the invention
teaches the administration of a therapeutic combination of ingredients
comprising of pterostilbene, nigella sativa, sulforaphane, and
epigallocatechin-3-gallate (EGCG) to a mammal at risk of infection with
SARS-CoV-2. In another embodiment, the invention teaches administration of said
therapeutic combination to a mammal infected with said SARS-CoV-2. In some
embodiments dosage of said therapeutic combination is based on inflammatory
and/or immunological parameters observed in patients with COVID-19. Granted on
March 8, 2022, https://patents.justia.com/patent/11266707
On November 4, 2019, the Company filed a patent application titled "Cellular,
Organ, and Whole-Body Rejuvenation Utilizing Cord Blood Plasma and
Pterostilbene" that disclosed methods, means, and protocols for stimulation of
rejuvenation in single cells, organs, and organisms by administration of cord
blood derived plasma, cord blood plasma concentrates, and cord blood derived
exosomes together with pterostilbene. The invention describes the previously
unexpected finding that addition of pterostilbene to cord blood enhances the
rejuvenation properties of cord blood. Said rejuvenation properties include
telomere preservation, reduction in beta galactosidase, and retention of
cellular activities.
Published on May 6, 2021, https://patents.justia.com/patent/20210128638
On September 9, 2019, the Company filed a patent application titled
"Pterostilbene and Formulations Thereof for Protection of Hematopoiesis from
Chemotherapy and Radiation" which disclosed compositions of matter useful for
treatment and/or prevention of hematopoietic injury using pterostilbene and
formulations thereof. In one embodiment nanoparticle delivered pterostilbene is
administered subsequent to chemotherapy induced neutropenia in order to
accelerate recovery of the hematopoietic compartment. In another embodiment,
pterostilbene is provided concurrently with chemotherapy in order to
concurrently assist the neoplasia killing action of the chemotherapy while
protecting the bone marrow from suppression. In contrast to conventionally used
agents that protect from neutropenia such as G-CSF and GM-CSF, the products
disclosed can be chronically administered, thus allowing for concurrent use with
chemotherapeutic or radiotherapeutic agents.
On January 21, 2019, the Company filed a patent application titled "Prevention
and Reversion of Chronic Traumatic Encephalopathy through Administration of
"Educated" Monocytes and Progenitors Thereof" that provides means of preventing
and/or reversing chronic traumatic encephalopathy in a patient through the
modulation of monocytes as well as monocytic progenitors. In one embodiment the
invention teaches administration of monocytes that have been previously
"educated" by exposure to mesenchymal stem cells in order to endow onto said
monocytes properties associated with stimulation of neuroregenerative
properties. In some embodiments monocytes are educated by treatment of monocytic
progenitors with conditions capable of endowing anti-inflammatory and
regenerative conditions, said conditions include culture with epigenetic
modifying agents. In other embodiments, the invention teaches the manipulation
of cord blood derived monocytes as a starting population of cells for education
by culture with mesenchymal stem cells.
On January 21, 2019, the Company filed a patent application titled "Autologous
Neurogenic Cells and Uses Thereof for Professional Athletes at Risk of Chronic
Traumatic Encephalopathy" which disclosed are means, compositions of matter and
methods of business for treating Chronic Traumatic Encephalopathy (CTE) using
autologous primary cells and modified cells of autologous origin which have been
banked. In one embodiment of the invention autologous dedifferentiation cells
are generated and stored for future administration in patients which have
suffered CTE. In other embodiments, dedifferentiated cells are differentiated
into neurons or neuronal progenitor cells and subsequently administered locally
or systemically or in a combination. In other embodiments autologous cells are
maintained in an undifferentiated manner and/or neurologically differentiated
state and utilized as a conditioning source in an extracorporeal circulatory
system replicating clinical stage extracorporeal liver perfusion (ECLP) with
substitution of autologous dedifferentiated, neurologically differentiated or a
combination of said cells instead of hepatic cells.
13
On December 18, 2018, the Company filed a patent application titled "Treatment
of Chronic Traumatic Encephalopathy via RNA Administration" which disclosed are
protocols, treatment means, and compositions of matter useful for treatment of
Chronic Traumatic Encephalopathy through administration of RNA or modified RNA
molecules. In one embodiment said RNA is generated to activate various toll like
receptors (TLR), of which said activation leads to production of cytokines which
paradoxically lead to protection from Chronic Traumatic Encephalopathy, wherein
said protection constitutes a) reduction in glial cell activation, b) neuronal
apoptosis due to excitotoxicity; and c) stimulation of endogenous regenerative
processes including endothelial progenitor cell mobilization, proliferation of
neuronal progenitor cells in the dentate gyrus and subventricular zones. In one
particular embodiment targeting of RNA molecules is performed to specific brain
cells including pyramidal neurons through the use of liposomes, exosomes,
apoptotic bodies, nanoparticles and shark or cameloid antibodies is disclosed.
On September 25, 2018, the Company filed a patent application titled
"Pterostilbene and Formulations Thereof for Treatment of Pathological Immune
Activation" that teaches treatments, protocols, and compositions of matter are
described for reduction of pathological immune system activation. In one
embodiment, pterostilbene and/or formulations thereof are administered in a
patient suffering from cytokine release syndrome at a concentration and
frequency sufficient to reduce abnormal cytokine production and thus treat the
cause of said cytokine release syndrome. Formulations of pterostilbene are
disclosed for rapid release, enhanced biodistribution, and targeting to cytokine
releasing effectors are disclosed for use in the practice of the invention.
On September 17, 2018, the Company filed a patent application titled
"Pterostilbene and Compositions Thereof for Prevention and Treatment of Chronic
Traumatic Encephalopathy" that teaches means, methods, and compositions of
matter useful for prevention of chronic traumatic encephalopathy. In one
embodiment of the invention, disclosed is utilization of pterostilbene and/or
pterostilbene based compounds for prevention and/or treatment of chronic
traumatic encephalopathy. In one embodiment, the invention teaches
administration of pterostilbene and/or pterostilbene based compounds for
reduction of taupathy associated with chronic traumatic encephalopathy.
On August 13, 2018, the Company filed a patent application titled "Enhancement
of Ozone Therapy using Pterostilbene" that disclosed methods, means and
compositions of matter using pterostilbene for enhancing therapeutic efficacy of
ozone therapy in the field of oncology. The invention provides previously
unknown synergies between ozone administration together with pterostilbene at
inducing direct and indirect cytotoxicity to cancer cells. The invention
provides means of delivery, administration, and therapeutic protocols for
treatment of cancer patients. In one embodiment combination of ozone therapy
together with pterostilbene is utilized to overcome drug resistance.
On October 08, 2017, the Company filed a patent application titled "Synergistic
Inhibition of Glioma Using Pterostilbene and Analogues Thereof" that teaches
methods, means and compositions of matter for utilizing pterostilbene and
analogues thereof for suppression of viability, metastasis and proliferation of
glioma cells alone, or together with immunotherapy, chemotherapy, or
radiotherapy means. In one embodiment said pterostilbene augments immunogenicity
of glioblastoma cells so as to enhance killing by immune cells or complement
subsequent to damage of said glioblastoma cells by chemotherapy, radiotherapy,
or immunotherapy.
On April 26, 2017, the Company filed a patent application titled "Augmentation
of Stem Cell Activity using Pterostilbene and Compositions Containing
Pterostilbene" that disclosed means of augmenting circulating endogenous stem
cells through administration of an effective amount of pterostilbene or
derivatives thereof. In one embodiment a patient with reduced levels of
circulating endothelial progenitor cells is treated with pterostilbene at a
concentration and frequency sufficient to restore, and/or enhance levels of
circulating endothelial progenitor cells (EPC). In another embodiment endogenous
levels of stem cells are restored or enhanced by administration of
pterostilbene, said endogenous stem cells comprising cells of the dentate gyrus,
subventricular zone, hepatic stem cells, cardiac stem cells, and hematopoietic
stem cells.
On March 29, 2017, the Company filed a patent application titled "Stimulation of
Immunity to Tumor Stem Cell Specific Proteins by Peptide Immunization" that
discloses treatment of cancer is disclosed through administration of proteins or
specific peptides found on tumor stem cells in vivo, in a matter eliciting
monocyte or dendritic cell migration in order to allow uptake of said
administrated proteins or peptides, followed by administration of a maturation
signal in vivo. The invention provides for treatment of cancer through induction
of anticancer immunity and/or immunity towards tumor initiating stem cells.
On March 29, 2017, the Company filed a patent application titled "Targeting the
Tumor Microenvironment through Nutraceutical Based Immunoadjuvants" that
disclosed compositions useful for the treatment of cancer which modulate tumor
associated immunosuppression, thus acting as immunoadjuvants. In one embodiment
a composition containing apigenin, is provided, said composition useful for
inhibition of tumor associated immune suppression mediated through the molecule
indolamine 2,3 deoxygenase (IDO). In another embodiment, liposomal apigenin is
administered as a means of decreasing IDO expression.
On March 29, 2017, the Company filed a patent application titled "Activated
Leukocyte Extract for Repair of Innate Immunity in Cancer Patients" that
disclosed are compositions, methods of use, and pharmaceutical preparations
useful for modulation of immune responses. In one embodiment a composition is
extracted polyvalently activated peripheral blood mononuclear cells through
dialysis. Said immune modulator is useful for treatment of cancer and
alleviation of cancer associated immune depression. In one embodiment, said
immunomodulator acts as a costimulatory of T cell activation by modulation of
cytokine production. In one embodiment said immune modulator is concentrated for
miRNA species capable of activating innate immune cells.
14
On March 29, 2017, the Company filed a patent application titled "Augmentation
of Anti-Tumor Immunity by Mifepristone and Analogues Thereof" which relates to
compositions of matter and methods useful for improving a treatment outcome
and/or an alteration of immunity in a condition that benefits from immune
stimulation. In particular, one embodiment of the invention teaches
administration of sufficient doses of mifepristone or a derivative, alone, or in
combination with an immunotherapeutic such as, but not limited to, an antibody,
a vaccine, a cytokine, or a medicament whose therapeutic activity is associated
with immune modulation.
On March 29, 2017, the Company filed a patent application titled "Methods of
Re-Activating Dormant Memory Cells with Anticancer Activity" that disclosed
methods, protocols, and compositions of matter useful for stimulation of
anticancer immune responses. In one embodiment of the invention culture of buffy
coat cells is performed in an environment resembling non-physiological
conditions. Buffy coat derived products are subsequently harvested,
concentrated, and added to a culture of monocytes and lymphocytes. Conditioned
media from said second culture is subsequently utilized as an injectable
solution for stimulation of anticancer immunity.
On March 29, 2017, the Company filed a patent application titled "Modulation of
Oral Microbiome for Treatment of Periodontitis" that disclosed methods, means,
and compositions of matter useful for inhibition of, reduction in progression
and reversion of periodontitis. In one embodiment the invention provides
prebiotic and/or probiotic compositions which modulation the oral microbiome in
order to ameliorate, prevent or reverse periodontitis. In one embodiment a
composition is administered into the oral cavity containing Actinomyces
naeslundii, Actinomyces odontolyticus, Streptococcus thermophilius,
Lactobaccilus brevis and Lactobacilius plantarum. Administration may be
performed using various means including a mouthwash, a patch, a toothpaste, or
in a preferred embodiment said prebiotic and/or probiotic compositions are
delivered via a mouth tray.
On July 20, 2016, the Company filed a patent application titled "Prevention of
Pregnancy Complications by Probiotic Administration" which disclosed methods,
protocols and compositions of matter for the treatment of pregnancy
complications through immune modulation of a mammal in need. In one embodiment
the invention provides probiotic compositions for immune modulation to decrease
risk of pregnancy complications. Pregnancy complications include recurrent
spontaneous abortions (RSA), preterm birth, pre-eclampsia including hemolysis
elevated liver enzymes low platelets (HELP), premature rupture of the membrane,
Antepartum hemorrhage including placental abruption, chorioamnionitis,
Intrauterine growth restriction, placenta pravaevia, sequalae of intraamniotic
infection. Published on January 26, 2017,
https://patents.justia.com/patent/20170020930
On July 20, 2016, the Company filed a patent application titled "Exosome
Mediated Innate and Adaptive Immune Stimulation for Treatment of Cancer" that
teaches means of stimulating innate and/or adaptive immunity to cancer by
administration of exosomes. Stimulation of innate immunity involves modifying
exosomes by chemical addition of innate immune stimulators, whereas stimulation
of adaptive immunity involves pulsing dendritic cells generating exosomes with
antigens, in some cases, pulsing with Brother of the Regulator of Imprinted
Sites (BORIS) proteins, peptides, or altered peptide ligands thereof.
On July 8, 2015, the Company filed a patent application titled "Augmentation of
Oncology Immunotherapies by Pterostilbene Containing Compositions" that
disclosed compositions of matter and methods useful to augmentation of immune
responses to tumors. In one embodiment, a pterostilbene containing composition
is administered to a cancer patient at a sufficient concentration and frequency
to induce de-repression of tumor targeting immune responses. In one specific
embodiment of the present invention, pterostilbene enhances antibody dependent
cellular toxicity (ADCC) and in turn augments efficacy of FDA approved antigen
specific immunotherapeutics such as trastuzumab (Herceptin) and other monoclonal
antibody therapies used for treating cancer.
Issued and Granted Patents:
On June 20, 2017, the US Patent and Trademark Office issued and granted U.S.
Patent No.: 9,682,047 titled "Augmentation of oncology immunotherapies by
pterostilbene containing compositions" that discloses compositions and methods
useful to enhancing, improving, or eliciting anti-tumor immune responses are
disclosed. A pterostilbene containing composition is administered to a cancer
patient at a sufficient concentration and frequency to induce de-repression of
tumor targeting immune responses. The composition enhances antibody dependent
cellular toxicity (ADCC) and augments efficacy of antigen specific
immunotherapeutics such as trastuzumab and other monoclonal antibody therapies
useful for treating cancer.
See: https://patents.justia.com/patent/9682047.
On January 25, 2022, the US Patent and Trademark Office issued and granted U.S.
Patent No.: 11,229,674 titled "Nutraceuticals for suppressing indolamine 2,3
deoxygenase" which disclosed are compositions of matter, treatments and
protocols useful for reduction of expression and/or activity of indolamine 2,3
deoxygenase (IDO). In some embodiments the invention teaches the administration
of a therapeutic combination of ingredients comprising of pterostilbene, Nigella
sativa, sulforaphane, and epigallocatechin-3-gallate (EGCG) to a mammal at
possessing an increased expression and/or activity of said IDO in which
reduction of number and/or activity is desired. In another embodiment, the
invention teaches administration of said therapeutic combination to a mammal
infected with viral and/or bacterial infections and/or neoplasia. In some
embodiments dosage of said therapeutic combination is based on inflammatory
and/or immunological parameters observed in patients.
See: https://patents.justia.com/patent/11229674.
15
On March 08, 2022, the US Patent and Trademark Office issued and granted U.S.
Patent No.: 11,266,707 titled "Nutraceuticals for the prevention, inhibition,
and treatment of SARS-CoV-2 and associated COVID-19" that disclosed methods of
treating or preventing complications associated with a SARS-CoV-2 infection,
comprising: administration of a combination comprising: a) Green Tea and/or
extract thereof; b) Blueberry and/or extract thereof; c) Nigella sativa and/or
extract thereof; and d) broccoli and/or extract thereof in an amount and
frequency sufficient to treat or prevent complications associated with said
SARS-CoV-2 infection.
See: https://patents.justia.com/patent/11266707.
*The data provided here is partial and does not contain all materials submitted
for publication and is preliminary until peer review is complete. These
statements have not been evaluated by the Food and Drug Administration. These
products are not intended to diagnose, treat, cure, or prevent any disease.
Chronic Traumatic Encephalopathy (CTE), and Traumatic Brain Injury (TBI) - Right
To Try
On December 10, 2018, Therapeutic Solutions International, Inc., announced the
signing of an agreement between TSOI and Jadi Cell LLC for licensing of the Jadi
Cell universal donor adult stem cell, as covered in US Patent No.: 9,803,176 B2
for use in Chronic Traumatic Encephalopathy (CTE), and Traumatic Brain Injury
(TBI).
In addition, on February 9, 2021, we obtained exclusive rights under the same
for use of US Patent No.: 9,803,176 B2 in the treatment of acute respiratory
distress syndrome (ARDS) and other lung pathologies. The JadiCell was reported
in a publication from the University of Miami following a Phase 1/2 clinical
trial, demonstrating intravenous administration of JadiCells, resulted in a
significant survival improvement in COVID-19 patients. The Phase 1/2 double
blind, placebo-controlled trial treated 12 advanced COVID-19 patients with 100
million JadiCells™ intravenously at days 0 and 3, and 12 patients received
placebo control. At 28 days 91% of JadiCell treated patients survived whereas
only 42% of patients in the placebo group survived. There were no adverse
effects associated with JadiCell administration. For those treated with the
JadiCell under the age of 85 the survival rate was 100% and in those over 85 the
survival rate was 91% making the JadiCell the most effective therapy to date in
the entire world to treat ARDS.
The JadiCell product, which belongs to the mesenchymal stem cell (MSC) family of
cells, is a unique adult stem cell, which produces higher levels of therapeutic
factors compared to other stem cells. The cells have demonstrated safety in
animal models and pilot human trials. The Jadi Cell product is generated from
umbilical cords, which are a source of medical waste and available in large
quantities at inexpensive prices.
Chronic Traumatic Encephalopathy (CTE) is caused by repetitive
concussive/sub-concussive hits to the head sustained over a period of years and
is often found in football players. The condition is characterized by memory
loss, impulsive/erratic behavior, impaired judgment, aggression, depression, and
dementia. In many patients with CTE, it is anatomically characterized by brain
atrophy, reduced mass of frontal and temporal cortices, and medial temporal
lobe.
Traumatic brain injury (TBI) is an insult to the brain, not of a degenerative or
congenital nature, but caused by external physical force that may produce a
diminished or altered state of consciousness, which results in an impairment of
cognitive abilities or physical functioning.
CTE represents a significant unmet medical need which we believe is amenable to
stem cell intervention. We are eager to accelerate treatments and potential
cures for debilitating conditions such as CTE and traumatic brain injury and
plan to leverage New regulatory pathways such as the recently approved "Right to
Try" Law to deliver these medicines as soon as possible to patients which
currently have no other options.
The JadiCell product because of its advanced stage of development in contrast to
other stem cell types, which require years, if not decades of development before
entry into American patients, will allow us we believe to be treating patients
within 12 months. Currently means of isolating, producing, scaling up, and
delivery of the cells has all been worked out by Jadi Cell and Collaborators.
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On December 17, 2020, the Company filed an Investigational New Drug (IND)
application seeking permission from the Food and Drug Administration (FDA) to
initiate a Phase I/II clinical trial assessing safety and signals of efficacy
for treatment of Chronic Traumatic Encephalopathy (CTE) patients with
JadiCells™.
On August 4th, 2021, the Company announced clearance from the Food and Drug
Administration (FDA) to initiate a Phase III pivotal trial for registration of
the Company's JadiCell universal donor stem cell as a treatment for COVID-19
associated lung failure under IND # 19757. In previous studies the Company has
demonstrated the superior activity of JadiCell to other types of stem cells
including bone marrow, adipose, cord blood, and placenta. Furthermore, the
JadiCell was shown to be 100% effective in saving the lives of COVID-19 patients
under the age of 85 in a double-blind placebo controlled clinical trial with
patients in the ICU on a ventilator. In patients over the age of 85 the survival
rate was 91%. The Company also recently announced the launching of Phase III for
IND # 19757 with Biorasi LLC, a global, full-service CRO, who will run the
clinical trial.
Schizophrenia/Suicide Clinical Programs
On October 29, 2020, the Company announced publication on the NIH clinical
trials website of its newly initiated trial aiming to validate a blood-based
diagnostic for predicting suicide risk and is listed as NCT04606875.
The Campbell Score™, which is a patent-pending method of quantifying
inflammatory-associated biological markers, has previously been shown in pilot
investigator-initiated studies to correlate with propensity for suicide. Based
on positive feedback from collaborators, the Company decided to initiate a
formal clinical trial to validate correlations between the Campbell Score™ and
established psychiatric assessment tools of suicidal propensity. Currently the
only means of quantifying predisposition to suicide is based on psychological,
question-based techniques.
On December 31, 2020, the Company signed license agreements with Campbell
Neurosciences Inc., a partially owned company, for access to the 9 patents filed
related to the previous Campbell Neurosciences Division. The patents are:
1. 63/128759 Immunotherapy for Opioid Addiction
2. 63/122862 Treatment of Major Depressive Disorder and Suicidal Ideations
Through Stimulation of Hippocampal Neurogenesis Utilizing Plant-Based
Approaches
3. 63/105964 Protection/Regeneration of Neurological Function by Endothelial
Protection/Rejuvenation using Stem Cells for Treatment of Conditions such as
Chronic Traumatic Encephalopathy and Schizophrenia
4. 17/030416 Personalized Immunotherapies for Reduction of Brain Inflammation
and Suicide Prevention
5. 63/077723 Immunotherapy of Schizophrenia and Schizophrenia Associated
Suicidal Ideation/Suicide
6. 63/071381 Upregulation of Therapeutic T Regulatory Cells and Suppression of
Suicidal Ideations in Response to Inflammation by Administration of
Nutraceutical Compositions Alone or Combined with Minocycline
7. 63/068388 Methods of Determining Risk of Suicide and/or Suicidal Ideation by
Immunological Assessment
8. 63/061202 Prevention of Neuroinflammation associated Memory Loss Using
Nutraceutical Compositions
9. 63/057315 Neuroprotection and Neuroregeneration by Pterostilbene and
Compositions Thereof
Additionally, Campbell Neurosciences Inc. has entered into purchase agreements
with Therapeutic Solutions International ensuring a continued supply, at a
discounted rate, of nutraceuticals which are being explored for
antiinflammation/suicide prevention activity.
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Treatment of Chronic Obstructive Pulmonary Disease (COPD) Using JadiCell™
Universal Donor Adult Stem Cells
On October 7, 2022, the Company formed Breathe Biologics, Inc. and licensed to
them a patent application titled "Umbilical Cord Mesenchymal Stem Cells for
Treatment of Chronic Obstructive Pulmonary Disease and Lung Degeneration" that
discloses means of treating lung degenerative diseases including chronic
obstructive pulmonary disease (CODP) using umbilical cord mesenchymal stem cells
such as JadiCells.
In addition, the Company has transferred ownership of the filed investigational
drug application titled "JadiCell Therapy for COPD" to determine safety and
efficacy of intravenously administered allogeneic JadiCell umbilical cord blood
mesenchymal stem cells in patients with moderate-to-severe COPD. The Primary
Endpoint, which is toxicity, will be assessed by number of adverse events (AEs).
The Secondary Endpoint, which is efficacy will be evaluated at baseline and days
30, 60, and 90.
COPD is a consistently progressive, ultimately fatal disease for which no
treatment exists capable of either reversing or even interrupting its course. It
afflicts more than 5% of the population in many countries, and it accordingly
represents the third most frequent cause of death in the U.S., where it accounts
for more than 600 billion in health care costs, morbidity, and mortality.
COPD possesses several features making it ideal for stem cell-based
interventions: a) the quality of life and lack of progress demands the ethical
exploration of novel approaches. For example, bone marrow stem cells have been
used in over a thousand cardiac patients with some indication of efficacy.
Adipose-based stem cell therapies have been successfully used in thousands of
race-horses and companion animals without adverse effects, as well as numerous
clinical trials are ongoing and published human data reports no adverse effects.
Mesenchymal Stem Cells (MSCs) are potent immunomodulatory cells that recognize
sites of injury, limit effector T cell reactions, and stimulate regulatory cell
populations (i.e., T-regs) via growth factors, cytokines, and other mediators.
Simultaneously, MSCs also stimulate local tissue regeneration via paracrine
effects inducing angiogenic, anti-fibrotic and remodeling responses.
Consequently, MSCs-based therapy represents a viable treatment option for
autoimmune conditions and other inflammatory disorders, yielding beneficial
effects in models of autoimmune Type 1 Diabetes, Systemic Lupus Erythematosus,
Autoimmune Encephalomyelitis, Multiple Sclerosis, cardiac insufficiency, and
organ transplantation. MSCs have been reported to inhibit inflammation and
fibrosis in the lungs, have shown safety in clinical trials for ARDS, and have
been recently suggested as useful to treat patients with severe COVID-19 based
on their effects preventing or attenuating the immunopathogenic cytokine storm.
Unfortunately, evaluation of stem cell therapy in COPD has lagged behind other
areas of regenerative investigation; b) the underlying cause of COPD appears to
be inflammatory and/or immunologically mediated. The destruction of alveolar
tissue is associated with T cell reactivity, pathological pulmonary macrophage
activation, and auto-antibody production. Mesenchymal stem cells have been
demonstrated to potently suppress autoreactive T cells, inhibit macrophage
activation, and autoantibody responses. Additionally, mesenchymal stem cells can
be purified in high concentrations from adipose stromal vascular tissue together
with high concentrations of T regulatory cells, which in animal models are
approximately 100 times more potent than peripheral T cells at secreting
cytokines therapeutic for COPD such as IL-10. Additionally, use of adipose
derived cells has yielded promising clinical results in autoimmune conditions
such as multiple sclerosis; and c) Pulmonary stem cells capable of regenerating
damaged parenchymal tissue have been reported. Administration of mesenchymal
stem cells into neonatal oxygen-damaged lungs, which results in COPD-like
alveoli dysplasia, has been demonstrated to yield improvements in two recent
publications.
Based on the above rationale for stem cell-based COPD treatments, we are
proposing a 10 patient Phase I safety trial to assess ability of JadiCell, a
type of umbilical cord derived stem cells to improve objective and quality of
life parameters in patients with moderate to severe COPD.
MSCs can be derived in large number from the Umbilical Cord (UC). JadiCells are
a type of UC-MSCs, which can be utilized in the allogeneic setting and have
demonstrated safety and efficacy in clinical trials for a number of disease
conditions including inflammatory and immune-based diseases. UC-MSCs have been
shown to inhibit inflammation and fibrosis in the lungs.
18
JadiCell UC-MSCs have been utilized to treat patients with severe COVID-19 and
have yielded promising results, preventing, or attenuating the cytokine storm.
JadiCells have been recently introduced intravenously in patients with a
neurodegenerative disorder and have been approved for testing in patients with
Type 1 Diabetes (TlD). We hypothesize that JadiCells will exert beneficial
therapeutic effects in COPD.
Breast Cancer Immunotherapy
Recently the Company announced the formation of a Spin-Off Company, Res Nova
Bio, Inc., dedicated to the development of cancer inhibiting anti-angiogenesis
immunotherapies. Res Nova Bio has licensed from Therapeutic Solutions
International intellectual property covering StemVacs-V which is our iPSC
derived platform technology announced in May of 2021. The technology utilizes
pluripotent stem cells called iPSCs in order to generate new cells which
resemble tumor blood vessels that are made to act as a "therapeutic vaccine".
Specifically, the administration of StemVacs-V stimulates the immune system to
selectively kill blood vessels that feed the tumor but not healthy blood
vessels. It is believed that for every 1 tumor blood vessel cell that is killed,
200-300 tumor cells are also killed as a result.
In addition to the license, the Company has transferred ownership of the IND
titled "Treatment of Metastatic Breast Cancer by StemVacs-V Cancer
Immunotherapeutic" to Res Nova Bio with the primary objective being safety and
feasibility of StemVacs-V administration at 12 months as assessed by lack of
adverse medical events. The secondary objective is efficacy as judged by tumor
response, time to progression, and immunological monitoring.
Cellular Manufacturing and Cell Banking
On October 18, 2021, the Company announced the formation of Allogen Biologics
Inc, a wholly owned subsidiary of TSOI. Allogen Biologics will house
intellectual property and Standard Operating Procedures related to generation of
the Company's existing and anticipated cellular therapeutics. In addition,
Allogen will house and maintain all relevant cell banks.
On May 10, 2022, Allogen Biologic, Inc, and Therapeutic Solutions International
Inc, entered into an Exclusive Patent License Agreement (EPLA) for Patent
Application Serial No. 63/254,469, filed by Licensor and titled as: Umbilical
Cord Derived Regenerative and Immune Modulatory Stem Cell Populations.
GOVERNMENT REGULATION
The Company's business is subject to varying degrees of regulation by a number
of government authorities in the United States, including the United States Food
and Drug Administration (FDA), the Federal Trade Commission (FTC), and the
Consumer Product Safety Commission. The Company will be subject to additional
agencies and regulations if it enters the manufacturing business. Various
agencies of the state and localities in which we operate and in which our
products are sold also regulate our business, such as the California Department
of Health Services, Food and Drug Branch. The areas of our business that these
and other authorities regulate include, among others:
? product claims and advertising;
? product labels;
? product ingredients; and
? how we package, distribute, import, export, sell and store our products.
The FDA, in particular, regulates the formulation, manufacturing, packaging,
storage, labeling, promotion, distribution and sale of vitamins and other
nutritional supplements in the United States, while the FTC regulates marketing
and advertising claims. The FDA issued a final rule called "Statements Made for
Dietary Supplements Concerning the Effect of the Product on the Structure or
Function of the Body," which includes regulations requiring companies, their
suppliers and manufacturers to meet Good Manufacturing Practices in the
preparation, packaging, storage and shipment of their products. Management is
committed to meeting or exceeding the standards set by the FDA.
19
The FDA has also issued regulations governing the labeling and marketing of
dietary and nutritional supplement products. They include:
? the identification of dietary or nutritional supplements and their nutrition
and ingredient labeling;
? requirements related to the wording used for claims about nutrients, health
claims, and statements of nutritional support;
? labeling requirements for dietary or nutritional supplements for which "high
potency" and "antioxidant" claims are made;
? notification procedures for statements on dietary and nutritional supplements;
and
? pre-market notification procedures for new dietary ingredients in nutritional
supplements.
The Dietary Supplement Health and Education Act of 1994 (DSHEA) revised the
existing provisions of the Federal Food, Drug and Cosmetic Act concerning the
composition and labeling of dietary supplements and defined dietary supplements
to include vitamins, minerals, herbs, amino acids and other dietary substances
used to supplement diets. DSHEA generally provides a regulatory framework to
help ensure safe, quality dietary supplements and the dissemination of accurate
information about such products. The FDA is generally prohibited from regulating
active ingredients in dietary supplements as drugs unless product claims, such
as claims that a product may heal, mitigate, cure or prevent an illness, disease
or malady, trigger drug status.
The Company is also subject to a variety of other regulations in the United
States, including those relating to taxes, labor and employment, import and
export, and intellectual property.
Critical Accounting Policies and Estimates
The discussion and analysis of our financial condition and results of operations
are based on our unaudited condensed consolidated financial statements, which
have been prepared in accordance with U.S. generally accepted accounting
principles. The preparation of these unaudited condensed consolidated financial
statements requires us to make estimates and judgments that affect the reported
amounts of assets, liabilities, revenues and expenses, and related disclosure of
contingent assets and liabilities. We evaluate our estimates on an ongoing
basis. We base our estimates on historical experience and on other assumptions
that we believe to be reasonable under the circumstances, the results of which
form the basis for making judgments about the carrying values of assets and
liabilities that re not readily apparent from other sources. Actual results may
differ materially from these estimates under different assumptions or
conditions.
Recent Accounting Pronouncements
Recent accounting pronouncements are disclosed in Note 2 to the accompanying
unaudited condensed consolidated financial statements included in Item 1 of this
Quarterly Report on form 10-Q.
Results of Operations
You should read the following discussion of our financial condition and results
of operations together with the unaudited financial statements and the notes to
the unaudited financial statements included in this quarterly report. This
discussion contains forward-looking statements that reflect our plans, estimates
and beliefs. Our actual results may differ materially from those anticipated in
these forward-looking statements.
Overview
Currently the Company is focused on immune modulation for the treatment of
several specific diseases. Immune modulation refers to the ability to upregulate
(make more active) or downregulate (make less active) one's immune system.
Activating one's immune system is now an accepted method to treat certain
cancers, reduce recovery time from viral or bacterial infections and to prevent
illness. Additionally, inhibiting one's immune system is vital for reducing
inflammation, autoimmune disorders and allergic reactions.
20
TSOI is developing a range of immune-modulatory agents to target certain
cancers, schizophrenia, suicidal ideation, traumatic brain injury, and for daily
health.
Nutraceutical Division - TSOI has been producing high quality nutraceuticals.
Its current flagship product, QuadraMune®, is a multi-patented synergistic blend
of pterostilbene, sulforaphane, epigallocatechingallate, and thymoquinone.
QuadraMune has been shown to increase Natural Killer Cell activity and healthy
Cytokine production. Our synergistic blend of ingredients help the immune system
fight off common and complex ailments and promote healthy T Cell activity.
Recently the Company was approved to sell certain nutraceuticals on the Amazon
Platform.
Cellular Division - TSOI recently obtained exclusive rights to a patented adult
stem cell for development of therapeutics in the area of chronic traumatic
encephalopathy (CTE), traumatic brain injury (TBI), and lung pathology.
For the three and nine months ended September 30, 2022, and 2021
We had net loss of $946,462 for the three months ended September 30, 2022,
compared to a net loss of $814,799 for the three months ended September 30,
2021, an increase of $131,663. This increase was mainly due to increases in
general and administrative expenses, salaries, wages and related costs and
research and development expenses. We had net loss of $1,638,964 for the nine
months ended September 30, 2021, compared to a net loss of $2,738,142 for the
nine months ended September 30, 2022, an increase of $1,099,178. This increase
was mainly due to general and administrative expenses and research and
development expenses.
Net sales increased $17,250, from $57,291 to $74.541, for the three months ended
September 30, 2021 and September 30, 2022, respectively. Net sales increased
$96,392, from $101,796 to $198,188, for the nine months ended September 30, 2021
and September 30, 2022, respectively.
Cost of goods sold decreased $3,641 from $12,431 to $8,790, for the three months
ended September 30, 2021 and September 30, 2022, respectively. These decreases
were mainly a result of the efficiency in manufacturing the products for
products in 2022 and 2021. Cost of goods sold increased $5,839, from $27,598 to
$33,437, for the nine months ended September 30, 2021 and September 30, 2022,
respectively. These increases were mainly a result of the increases in net sales
for products in 2022 and 2021.
Operating expenses for the three-month periods ended September 30, 2022 and 2021
were $784,970 and $746,863, an increase of $38,107. This increase was mainly due
to increases in general and administrative expenses and research and development
expenses. Operating expenses for the nine-month periods ended September 30, 2022
and 2021 were $2,486,052 and $1,460,554, an increase of $1,025,498. This
increase was mainly due to general and administrative expenses, consulting,
legal and professional fees, and research and development expenses.
General and administrative expenses increased $173,567, from $31,271 to $204,838
for the three months ended September 30, 2021 and 2022, respectively. General
and administrative expenses increased $291,839, from $96,722 to $388,561 for the
nine months ended September 30, 2021 and 2022, respectively. This increase was
mainly attributable to an increase in expenses during the three and nine months
ended September 30, 2022.
Salaries, wages, and related expenses decreased $26,140, from $83,968 to
$110,108 for the three months ended September 30, 2021 and 2022, respectively.
This decrease was mainly due to a decrease in wage related expenses for the
three months ended September 30, 2022. Salaries, wages, and related expenses
increased $17,728, from $319,198 to $336,926 for the nine months ended September
30, 2021 and 2022, respectively. This increase was mainly due to an increase in
wage related expenses for the three and nine months ended September 30, 2022.
Consulting fees decreased $19,356 from $107,514 to $88,158 for the three months
ended September 30, 2021 and 2022, respectively, due to a decrease in overall
consulting services. Consulting fees increased $92,440 from $224,844 to $317,284
for the nine months ended September 30, 2021 and 2022, respectively, due to an
increase in overall consulting services.
Legal and professional fees decreased $385,500 from $492,295 to $106,795 for the
three months ended September 30, 2021 and 2022, respectively, due to decrease in
legal expense. Legal and professional fees decreased $370,035, from $636,193 to
$266,158 for the nine months ended September 30, 2021 and 2022. These decreases
were mainly related to legal expenses during the nine months ended September 30,
2022.
21
Research and development increased $243,256, from $31,815 to $275,071 for the
three months ended September 30, 2021 and 2022, respectively, due to an increase
in research and development. Research and development increased $993,526, from
$183,597 to $1,177,123 for the nine months ended September 30, 2021 and 2022.
These increases were mainly related to research and development expenses during
the three and nine months ended September 30, 2022.
Loss on derivatives liability decreased approximately $18,139, from $45,006 to
$26,867 for the three months ended September 30, 2021 and 2022, respectively.
This decrease was mainly due to a decrease in the amount of new convertible
notes being issued during the current period. Loss on derivatives liability
decreased approximately $340,976, from $477,559 to $136,583, for the nine months
ended September 30, 2021 and 2022, respectively This decrease was mainly due a
decrease in the amount of new convertible notes being issued during the current
nine-month period.
Change in fair derivatives liabilities gains decreased approximately $85,829
from a gain of $53,624 to a loss of $32,205 for the three months ended September
30, 2021 and 2022, respectively. This decrease was largely due to a decrease in
the balance of convertible notes outstanding upon which the derivative liability
is recorded. Change in fair derivatives liabilities gains decreased $391,073
from $624,376 to $233,303 for the nine months ended September 30, 2021 and 2022,
respectively. This decrease was largely due to a decrease in the balance of
convertible notes outstanding upon which the derivative liability is recorded.
Net interest expense increased $45,957 from $121,414 to $167,371 for the three
months ended September 30, 2021 and 2022 respectively. This increase was mainly
due to increased debt balances. Net interest expense increased $113,336 from
$399,425 to $512,761 for the nine months ended September 30, 2021 and 2022,
respectively. This increase was mainly due to increased debt balances.
Liquidity and Capital Resources
We have experienced recurring losses over the past years which have resulted in
accumulated deficits of approximately $16.7 million and a working capital
deficit of approximately $1.9 million at September 30, 2022. These conditions
raise significant doubt about the Company's ability to continue as a going
concern. The Company's ability to continue as a going concern is contingent upon
its ability to secure additional financing, increase sales of its products and
attain profitable operations. It is the intent of management to continue to
raise additional capital. However, there can be no assurance that the Company
will be able to secure such additional funds or obtain such on terms
satisfactory to the Company, if at all.
There is no guarantee we will receive the required financing to complete our
business strategies, and it is uncertain whether future financing will be
available to us on acceptable terms. If financing is not available on
satisfactory terms, we may be unable to continue, develop or expand our
operations.
Off Balance Sheet Arrangements
We currently do not have any off-balance sheet arrangements.
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