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.
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).
4
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 JadiCellTM 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 JadiCellTM to other types of stem cells
including bone marrow, adipose, cord blood, and placenta. Furthermore, the
JadiCellTM 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 for a new hybrid cell
created by the Company capable of training the immune system to kill blood
vessels feeding cancer, but sparing healthy blood vessels. These discoveries are
an extension of previous findings from the Company showing that StemVacs is
capable of suppressing new blood vessel production.
On May 9, 2022, the Company filed an Investigational New Drug Application for
Treatment of Chronic Obstructive Pulmonary Disease (COPD) Using JadiCell™
Universal Donor Adult Stem Cells under IND Serial # 28508.
Investigational Drug Applications:
Treatment of Metastatic Breast Cancer by StemVacs-V Cancer Immunotherapeutic IND
# 28508
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.
5
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.
? 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:
TSOI filed a patent in July 2015 covering the use of its ProJuvenol® product, as
well as various pterostilbene compositions, for use in augmenting efficacy of
existing immuno-oncology drugs that are currently on the market. The patent is
based on the ability of pterostilbene, one of the major ingredients of
ProJuvenol®, to reduce oxidative stress produced by cancer cells, which in turn
protects the immune system from cancer mediated immune suppression. That patent,
U.S. No.: 9,682,047 was granted on 6-20-2017.
In addition, on April 28, 2016, the Company filed a patent application covering
the use of ProJuvenol© and its active ingredient pterostilbene for augmentation
of stem cell activity. Diseases such as diabetes, cardiovascular disease, and
neurodegenerative diseases are characterized by deficient stem cell activity.
The patent covers the stimulation of stem cells that already exist in the
patient's body, as well as stem cells that are administered therapeutically.
Studies have shown that patients who have higher levels of endogenous stem cell
activity have reduced cardiovascular disease risk and undergo accelerated
neurological recovery after stroke as compared to patients with lower numbers of
such stem cells.
On October 16, 2017, the Company filed a patent application titled "Synergistic
Inhibition of Glioma Using Pterostilbene and Analogues Thereof" which was
developed to utilize the ability of the immune system to augment the possibility
of increasing overall survival of glioma patients after treatment with
conventional therapies. Our data suggests that when pterostilbene is combined
with brain cancer therapeutics such as Gefitinib, Sertraline, or Temozolomide,
the prognosis is vastly improved.
On August 13, 2018, the Company filed a patent application titled "Enhancement
of Ozone Therapy using Pterostilbene" showing pterostilbene potently augments
killing of breast cancer, prostate cancer, and ovarian cancer cells by ozone
therapy. The data obtained is an extension of ongoing work at the Company
seeking to identify means of enhancing the effects of pterostilbene
administration for treatment of a variety of cancers, as well as enhancing the
efficacy of existing cancer therapies.
On September 17, 2018, the Company filed a patent application titled
"Pterostilbene and Compositions Thereof for Prevention and Treatment of Chronic
Traumatic Encephalopathy" with new data demonstrating the ability of its
NeuroStilbene intranasal formulation of pterostilbene to successfully prevent
the development of brain injury in an animal model of Chronic Traumatic
Encephalopathy aka CTE.
On September 25, 2018, the Company filed a patent application titled
"Pterostilbene and Formulations Thereof for Treatment of Pathological Immune
Activation" covering novel clinical data using its NanoStilbene™ formulation to
reduce inflammatory cytokine production in cancer patients.
On September 9, 2019, the Company filed a patent application titled
"Pterostilbene and Formulations Thereof for Protection of Hematopoiesis from
Chemotherapy and Radiation" covering the ability of NanoStilbene™ and its active
ingredient, pterostilbene, at accelerating recovery of blood cells after
treatment with chemotherapy.
6
On November 4, 2019, the Company filed a patent application titled "Cellular,
Organ, and Whole-Body Rejuvenation Utilizing Cord Blood Plasma and
Pterostilbene" suggesting that pterostilbene, the active ingredient in
commercially available NanoStilbene™, augments the ability of cord blood plasma
to suppress biological properties associated with aging.
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" developed to address issues of susceptibility, inflammation, and viral
immunity, for COVID-19 patients.
On May 11, 2020, the Company filed a patent application titled "Treatment of
COVID-19 Lung Injury Using Umbilical Cord Plasma Based Compositions" covers new
data in which combinations of pterostilbene and other compounds with cord blood
are shown to be capable of suppressing lung inflammation associated with
COVID-19 in an animal model.
On June 11, 2020, the Company filed a patent application titled "Nutraceuticals
for Reducing Myeloid Suppressor Cells" showing QuadraMune reduces the number and
activity of immune inhibitory cells termed "myeloid suppressor cells."
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.
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" with new
data showing its clinical-stage cancer immunotherapeutic product StemVacs™
appears to reduce innate immune induced inflammation in lungs while stimulating
immune cells known to possess antiviral properties. StemVacs™ is a cell-based
drug comprised of dendritic cells activated in a proprietary manner which when
administered stimulates a type of immune system cell termed "natural killer" or
NK cells. Numerous studies have shown that NK cells are involved in protecting
the body from cancer and from viruses. The FDA has allowed for clinical trials
of COVID-19 patients using an NK cell-based drug termed CYNK-001.
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.
On July 13, 2020, the Company filed a patent application titled "Prevention of
Pathological Coagulation in COVID-19 and other Inflammatory Conditions" with new
data showing that the ingredients of QuadraMune™ suppress expression of an
inflammation stimulated molecule which is known to induce coagulation of blood.
Inhibition of this coagulation-promoting molecule, called Tissue Factor, was
synergistic with all four ingredients of QuadraMune™ when combined. Tissue
Factor is known to be associated with COVID-19 disease and is the culprit for
clotting associated conditions such as deep vein thrombosis and
atherothrombosis.
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.
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.
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.
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.
7
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.
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 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.
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.
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.
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.
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.
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.
8
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.
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 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.
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 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 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 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 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.
9
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 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.
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 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 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 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 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 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.
10
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 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 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 can
not stimulate inflammation due to gene-editing based removal of inflammatory
associated transcription factors.
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.
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.: 11229674 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.
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.
11
Immune-Oncology - Right To Try
In May of 2018, President Donald J. Trump signed into the law, the Right To Try
bill. In 2015/2016 TSOI began and completed a 10 patient clinical trial of
advanced cancer patients in Mexico at the Pan Am Cancer Treatment Center located
in Tijuana Mexico using our dendritic cell vaccine code named StemVacs. TSOI has
since generated GCP documentation for the previously treated 10 patients into a
Phase I trial, which will be presented to the FDA by TSOI as part of an Ex-US
trial compliant with 21 CFR 312.120 Foreign clinical studies not conducted under
an IND. This is a required step to conform to the new Right To Try law.
StemVacs is an immunotherapy platform that consists of 5 components. The
overarching approach to the StemVacs Immunotherapy Platform is as follows:
1. Treat innate immune suppression: Administration of oral apigenin/NanoStilbene
(Cancer DeTox Product) to decrease immune suppressive toxic molecules made by
tumor and tumor microenvironment.
2. Treat adaptive immune suppression: Administration of MemoryMune to activate
dormant memory cells recognizing the tumor. Administration of LymphoBoost to
repair deficient IL-12 production.
3. Stimulation of immune response to cancer stem cells (StemVacs).
4. Consolidation and maintenance of immunity: Cycles of StemVacs, supported by
innaMune and LymphoBoost
StemVacs Autologous is a subcutaneously administered vaccine comprised of immune
stimulatory peptides resembling cancer stem cell specific proteins.
StemVacs Allogeneic is a subcutaneously administered vaccine comprised of immune
stimulatory peptides resembling cancer stem cell specific proteins.
Cancer Metabolic DeTox: This is an orally administered agent that is derived
from various herbs termed apigenin. The unique property of apigenin is that it
inhibits a cancer associated metabolic pathway that degrades the amino acid
tryptophan. Specifically, apigenin inhibits the enzyme indolamine 2,3
deoxygenase (IDO), which is responsible for breaking down tryptophan in the
vicinity of the tumor and generating by-products such as kynurenine. It is known
that immune activation is dependent on tryptophan being present in the tumor
environment. The depletion of tryptophan and generation of kynurenine by tumor
cells and tumor associated cells is a major cause of immune suppression in
cancer. By administering Cancer Metabolic DeTox, the innate arm of the immune
system has a chance to regenerate. This positions the patient for better outcome
after administration of specific immune stimulating vaccines.
MemoryMune: This is a product derived from a two-step culture process of donor
blood cells. The product MemoryMune reawakens dormant immune memory cells. It is
known that many cancer patients possess memory T cells that enter the tumor,
however, once inside the tumor these cells are inactivated. MemoryMune contains
a unique combination of growth factors specific for immune system cells called
"cytokines".
LymphoBoost: LymphoBoost is a proprietary formulation of Misoprostol, a drug
approved for another indication, which we have shown to be capable of
stimulating lymphocytes, particularly NK cells and T cells, both critical in
maintaining anti-tumor immunity.
innaMune: This is a biological product derived from tissue culture of blood
cells derived from healthy donors. It is a combination of cytokines that
maintain activity of innate immune system cells, as well as having ability to
shift M2 macrophages to M1.
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 JadiCellsTM intravenously at days 0 and 3, and 12 patients received
placebo control. At 28 days 91% of JadiCellTM treated patients survived whereas
only 42% of patients in the placebo group survived. There were no adverse
effects associated with JadiCellTM 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.
12
The Jadi Cell 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 Jadi Cell 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.
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 JadiCellTM 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 JadiCellTM to other types of stem cells
including bone marrow, adipose, cord blood, and placenta. Furthermore, the
JadiCellTM 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.
Sars/CoV2 Clinical Programs
On June 8, 2020, the Company announced the initiation of a clinical trial aimed
at demonstrating safety and efficacy of its immune-boosting formulation
QuadraMune™. The trial is anticipated to recruit 500 subjects at risk of
SARS-CoV-2 infection, the type of coronavirus which causes COVID-19. The new
clinical trial has been granted ClinicalTrials.gov Identifier: NCT04421391 and
is listed and registered on the Federal Clinical Trial registry.
The Company announced recently submission of a publication providing preclinical
data which supports repositioning of its Cancer Immunotherapy StemVacs™ as a
candidate for treatment of COVID-19. StemVacs™ is based on activating universal
donor immune system cells called dendritic cells in a manner so that upon
injection they reprogram the body's "Natural Killer" cells.
Natural killer cells are the most potent cell type in the body in terms of
killing viruses. Unfortunately, natural killer cells also produce chemicals
called cytokines which at high concentrations can be lethal. The current data
suggests that StemVacs™ can activate natural killer cells while at the same time
suppressing lung inflammation. This dual mechanism of action makes StemVacs™ a
promising candidate for treatment of coronavirus.
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.
13
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.
Treatment of Chronic Obstructive Pulmonary Disease (COPD) Using JadiCell™
Universal Donor Adult Stem Cells
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.
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 disorders, and have been approved for testing in patients with
Type 1 Diabetes (TlD). We hypothesize that JadiCells will exert beneficial
therapeutic effects in COPD.
The proposed clinical trial will recruit 10 patients of 40-80 years of age with
moderate to severe COPD (GOLD [Global Initiative for Chronic Lung Disease]. The
enrolled patients will be treated with 100 million JadiCells intravenously with
two injections spaced at 48 hours.
These two treatments will be performed on days 0 and 2. JadiCell dosing will be
performed at approximately 100 million cells/infusion delivered at a maximum
rate of 2 million cells/min per infusion.
Assessment of lung function and safety will be performed on days 0, 30, 60, and
90. Safety will be assessed by occurrence of adverse events (AEs) during either
study-drug infusion or by physician assessments and laboratory evaluations, a
record of COPD exacerbations will be maintained for each patient.
Efficacy measures will include improvement from baseline in pulmonary functions
(FEV 1 , FVC, FEV 1 /FVC, total lung capacity by plethysmography, 27
single-breath carbon monoxide diffusing capacity, exercise performance [6-min
walk test (6MWT)], and dyspnea assessment [Borg scale]), and QOL (St. George's
Respiratory Questionnaire, and global assessment of patient status). COPD
exacerbations were assessed as the time to the first exacerbation and as the
ratio of the rate of exacerbations between MSC- and placebo-treated patients.
14
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.
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.
15
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.
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
thymoquionone. 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 six months ended June 30, 2022 and 2021
We had net loss of $1,190,757 for the three months ended June 30, 2022, compared
to a net loss of $637,242 for the three months ended June 30, 2021, an increase
of $553,515. This increase was mainly due to increases in general and
administrative expenses, consulting, legal and professional fees, and research
and development expenses. We had net loss of $824,165 for the six months ended
June 30, 2021, compared to a net loss of $1,791,680 for the six months ended
June 30, 2022, an increase of $967,515. This increase was mainly due to general
and administrative expenses, consulting, legal and professional fees, and
research and development expenses.
Net sales increased $15,305, from $23,444 to $38,749, for the three months ended
June 30, 2021 and June 30, 2022, respectively. Net sales increased $79,142, from
$44,505 to $123,647, for the six months ended June 30, 2021 and June 30, 2022,
respectively.
Cost of goods sold increased $4,623 from $4,086 to $8,709, for the three months
ended June 30, 2021 and June 30, 2022, respectively. These increases were mainly
a result of the increases in net sales for products in 2022 and 2021. Cost of
goods sold increased $9,480, from $15,167 to $24,647, for the six months ended
June 30, 2021 and June 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 June 30, 2022 and 2021 were
$1,105,423 and $442,785, an increase of $662,638. This increase was mainly due
to increases in general and administrative expenses, consulting, legal and
professional fees, and research and development expenses. Operating expenses for
the six-month periods ended June 30, 2022 and 2021 were $1,701,082 and $713,691,
an increase of $987,391. This increase was mainly due to general and
administrative expenses, consulting, legal and professional fees, and research
and development expenses.
16
General and administrative expenses increased $115,076, from $28,640 to $143,716
for the three months ended June 30, 2021 and 2022, respectively. General and
administrative expenses increased $118,272, from $65,451 to $183,723 for the six
months ended June 30, 2021 and 2022, respectively. This increase was mainly
attributable to an increase in expenses during the three and six months ended
June 30, 2022.
Salaries, wages, and related expenses decreased $18,234, from $130,767 to
$112,533 for the three months ended June 30, 2021 and 2022, respectively. This
decrease was mainly due to a decrease in wage related expenses for the three
months ended June 30, 2022. Salaries, wages, and related expenses decreased
$8,412, from $235,230 to $226,818 for the six months ended June 30, 2021 and
2022, respectively. This decrease was mainly due to a decrease in wage related
expenses for the three and six months ended June 30, 2022.
Consulting fees increased $65,863 from $76,147 to $142,010 for the three months
ended June 30, 2021 and 2021, respectively, due to an increase in overall
consulting services. Consulting fees increased $111,796 from $117,330 to
$229,126 for the six months ended June 30, 2021 and 2022, respectively, due to
an increase in overall consulting services.
Legal and professional fees increased $34,125 from $75,146 to $109,271 for the
three months ended June 30, 2021 and 2022, respectively, due to an increase in
independent public accounting fees and legal expense. Legal and professional
fees increased $15,465, from $143,898 to $159,363 for the six months ended June
30, 2021 and 2022. These increases were mainly related to independent public
accounting fees and legal expenses during the six months ended June 30, 2022.
Research and development increased $465,808, from $132,085 to $597,893 for the
three months ended June 30, 2021 and 2022, respectively, due to an increase in
research and development. Research and development increased $750,270, from
$151,782 to $902,052 for the six months ended June 30, 2021 and 2022. These
increases were mainly related to research and development expenses during the
three and six months ended June 30, 2022.
Loss on derivatives liability decreased approximately $41,114, from $84,298 to
$43,184, for the three months ended June 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 increased
approximately $322,837, from $432,553 to $109,716, for the six months ended June
30, 2021 and 2022, respectively This decrease was mainly due a decrease in the
amount of new convertible notes being issued during the current six-month
period.
Change in fair derivatives liabilities gains increased approximately $56,636
from 66,566 to $123,202 for the three months ended June 30, 2021 and 2022,
respectively. This increase was largely due to an increase in the balance of
convertible notes outstanding upon which the derivative liability is recorded.
Change in fair derivatives liabilities gains decreased $305,244 from $570,752 to
$263,508 for the six months ended June 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 decreased $691 from $196,083 to $195,392 for the three
months ended June 30, 2021 and 2022 respectively. This decrease was mainly due
to decreased debt balances. Net interest expense increased $67,379 from $278,011
to $345,390 for the six months ended June 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 $15.7 million and a working capital
deficit of approximately $1.5 million at June 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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THERAPEUTIC SOLUTIONS INTERNATIONAL, INC. 