Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations
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, 2017 and the risk factors discussed therein.
General
Our principal executive office is located at 4093 Oceanside Blvd., Suite B, Oceanside, California 92056, 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
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.
TSI is developing a range of immune-modulatory agents to target certain cancers and diseases.
Nutraceutical Division
– TSI has been producing high quality nutraceuticals. Its flagship product, ProJuvenol
®
, is a proprietary mixture containing pterostilbene – one of the most potent antioxidants known. TSOI was granted U.S. Patent No.: 9,682,047 for ProJuvenol
®
on 06-20-2017.
Emvolio, Inc.
(“EMVO”) – is a wholly-owned subsidiary of TSI focused on developing products that can be used together to attack cancer at different levels, as well as to be used alone or in combination with existing therapies. Mr. Dixon and Mr. Berg, and Dr. Ichim, of the Company, are also officers and officers and/or directors of EMVO. As of November 14, 2018, formal operations have not commenced.
SandBox Dental Labs, Inc.
– is a wholly-owned subsidiary of TSI consisting of a dental laboratory to manufacture and fill prescriptions from dentists who will use our proprietary Sleep Appliance to treat their patients with mild to moderate obstructive sleep apnea. The Company has currently suspended its application in seeking regulatory approval for its device to treat sleep apnea. As of November 14, 2018, formal operations have not commenced.
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Nutraceutical Division (TSOI)
ProJuvenol
®
is a patented 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.
Nutraceutical 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.
On September 17, 2018 the Company filed a patent application titled “Pterostilbene and Compositions Thereof for Prevention and Treatment of Chronic Traumatic Encephalopathy” from 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.
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.
Pterostilbene
Pterostilbene
, (trans-3,5-dimethoxy-4-hydroxystilbene) is a stilbene compound that is structurally similar to other popular stilbenes such as resveratrol or piceatannol; it is named after its first discovered source (the pterocarpus genus) but is also a component of blueberries and grape products. It is a phytoalexin (compound produced by plants as a defense against parasites and insects) similar to resveratrol albeit more potent.
Pterostilbene
has been found to be significantly more stable in vivo than resveratrol, its half-life in vivo is approximately 104 minutes versus resveratrol, for 13 minutes. Further, studies indicate that the body better absorbs pterostilbene than resveratrol, and pterostilbene is more biologically active than resveratrol, and is more efficacious than resveratrol in inhibiting certain biological activities including pro-inflammatory enzymes (providing anti-inflammatory benefits), and cell membranes producing lipid peroxidation (providing anti-oxidant support).
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Each of the benefits below are specifically a growing concern within our targeted demographics, the availability of a natural product to the existing medical protocols provides a logical and affordable alternative, without many of the adverse side effects of traditional medicines.
Reduced insulin sensitivity
Reduction in VLDL and LDL (bad) cholesterol levels
Increasing HDL (good) cholesterol levels
Positive vascular smooth muscle cells
Anti-inflammatory benefits
Anti-oxidant benefits
Cognitive function improvement
Skin protection from Ultra Violet light exposure
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ProJuvenol
®
which contains 200mg of >99% pure Pterostilbene in each daily dose is powerful synergistic blend of complex anti-aging ingredients inspired by nature to help promote cellular rejuvenation and healthy functionality for everyday living. Based upon pterostilbene, one of nature's unique and intelligent antioxidants/anti-inflammatories. ProJuvenol® includes a scientifically valid blend of interactive ingredients with anti-aging and cellular protective properties to help support optimal health and provide the benefits of mental alertness and physical well-being.
ProJuvenol
®
was inspired by natures design and formulated to assist nature’s rejuvenation of the body's cells helping to slow and actually reverse the aging processes and decline in vitality. U.S. Patent No.: 9,682,047
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NanoStilbene
is prepared by low-energy emulsification which allows for better solubility, stability, and the release performance of pterostilbene nanoparticles. The pterostilbene placed in a nanoemulsion droplet is free from air, light, and hard environment; therefore, as a delivery system, nanoemulsion can not only improve the bioavailability of pterostilbene but also protect it from oxidation and hydrolysis, while it possesses an ability of sustained release at the same time.
A typical dose would be 5-10 milliliters yielding between 150 – 300 milligrams per dose. In addition to the benefits of the nanoparticle pterostilbene we chose to use medium chain triglycerides (MCT), derived from coconut oil, as one of our oil mediums in preparing the nanoemulsion.
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MCTs are not stored as fat, but rather convert quickly into Adenosine triphosphate (ATP), which provides energy for the body and brain at the cellular level.
MCT’s are also shown to increase metabolic thermo-genesis, improve stamina, endurance, athletic performance, and energy levels, as well as exhibiting potent anti-microbial properties – providing immune system benefits and helping in balancing candida in the gut.
NanoStilbene
is available in 150ml & 300ml bottles at a concentration of 30mg per ml with a recommended daily dose of 5ml – 10ml which is equal to 150-300mg.
Nanotechnology
Therapeutic uses of nanotechnology typically involve the delivery of small-molecule drugs, peptides, proteins, and nucleic acids. Nanoparticles have advanced pharmacological effects compared with the therapeutic entities they contain. Active intracellular delivery and improved pharmacokinetics and pharmacodynamics of drug nanoparticles depend on various factors, including their size and surface properties.
Nanoparticle therapeutics is an emerging treatment modality in cancer and other inflammatory disorders. The National Cancer Institute has recognized nanotechnology as an emerging field with the potential to revolutionize modern medicine for detection, treatment, and prevention of cancer.
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On May 15, 2018 TSI announced Institutional Review Board (IRB) clearance to initiate a pilot pharmacokinetic trial of “NanoStilbene.”
Then on July 02, 2018 the Company announced receiving pilot clinical data providing proof of concept that NanoStilbene more effectively increases blood levels of the molecule as compared to conventional formulations. The clinical trial involved the administration of NanoStilbene in comparison to powder in capsule form pterostilbene with healthy volunteers, whom underwent a series of blood draws to determine the concentration of the compound.
NanoStilbene Administration Results in Superior Pharmacokinetic Profile
Compared to Pterostilbene Administration
Blood was collected in EDTA tubes and plasma collected subsequent to centrifugation at 700g for 10 minutes. Collection time points were prior to administration of test compound, as well as at times 2hr, 4hr, 6hr, 8hr, 10hr, and 12 hrs. Test compounds were 10 ml of NanoStilbene (provided by Therapeutic Solutions International) and 6 capsules of 50 mg pterostilbene (VitaMonk). A wash out period of 3 days was allowed between two test compound administration.
The results were that at peak concentration NanoStilbene had a 55% increase in serum levels over the traditional powder form of pterostilbene. The data also shows the half-life to be double to that of the capsule form.
The data in Granted U.S. Patent No.: 9,682,047 strongly suggest that pterostilbene administration may be an inexpensive and safe method of augmenting efficacy of numerous immunotherapeutic drugs. Although cancer immunotherapy has revolutionized the prognosis of many patients, the majority of patients still possess poor or suboptimal responses to this approach.
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DermalStilbene
is delivered via spray application onto skin. This product contains DMSO (Dimethyl Sulfoxide) as a carrier and caution should be used not to spray product near eyes. Each 60ml bottle contains 300 applications of spray.
When using this product, you may notice some of the following; as spray lands on your skin you may feel heat sensation, and as the mist settles on your skin you may notice tingling or itching, this is all normal and will usually subside within 5 -10 minutes of use, although it can last longer. DermalStilbene is manufactured and sold under US Patent No.: 9,682,047
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As previously stated, pterostilbene has been demonstrated in numerous publications to possess therapeutic effects in animal models of numerous inflammatory-associated conditions including cancer, diabetes, and heart failure, but it has also been shown to “protect hairless mice against UVB radiation-induced skin damage and carcinogenesis
1
“, and “was able to reduce biofilm formation and kill the MRSA in immune cells by virtue of its strong antibacterial activity and facile delivery across biomembranes
2
”.
Pterostilbene is a more potent form of resveratrol, which both activate similar molecular pathways including SIRT-1. This protein called a “sirtuin” is known to possess anti-aging effects based on laboratory studies. While clinical studies have not been performed yet, it is not outside of the realm of possibility that pterostilbene based products may possess a beneficial effect on aging cells.
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IsoStilbene
an injectable formulation of pterostilbene under granted ‘047 Patent for Augmentation of Immunotherapy and Targeting of Cancer Stem Cells.
Peer reviewed publications have demonstrated efficacy of the pterostilbene molecule at stimulating immunity to cancer, as well as targeting cancer stem cells. Unfortunately, classical formulations of pterostilbene do not appear to deliver effective amounts of pterostilbene to cancer cells.
For this reason, Therapeutic Solutions International has developed several alternative dosing formulations including the previously discussed NanoStilbene, and now, IsoStilbene.
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NeuroStilbene
s delivered via spray application inside the nostril. Each 30ml bottle contains 300 applications of spray.
Intranasal delivery with the intention to deliver high concentrations of substances into the brain across what is called the “blood-brain barrier.” This structure is a “security system” that keeps blood cells separate from the fluid surrounding the brain. This barrier does provide oxygen and nutrients to be transported by the blood cells but prevents harmful substances like bacteria or poisons from getting to the brain. While compounds such as pterostilbene, and alpha lipoic acid, can bypass the BBB, it is anticipated that higher concentrations can be delivered through the intranasal route.
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FUTURE BUSINESS DESCRIPTION
Emvolio, Inc.
(“EMVO”) – is a wholly-owned subsidiary of TSI focused on developing products that can be used together to attack cancer at different levels, as well as to be used alone or in combination with existing therapies. Mr. Dixon and Mr. Berg, and Dr. Ichim, of the Company, are also officers and officers and/or directors of EMVO. As of November 14, 2018, formal operations have not commenced.
SandBox Dental Labs, Inc.
– is a wholly-owned subsidiary of TSI consisting of a dental laboratory to manufacture and fill prescriptions from dentists who will use our proprietary Sleep Appliance to treat their patients with mild to moderate obstructive sleep apnea. The Company has currently suspended its application in seeking regulatory approval for its device to treat sleep apnea. As of November 14, 2018, formal operations have not commenced.
On May 1, 2018 the Company licensed StemVacs to Pan Am Cancer Center in Tijuana, Mexico and on June 6, 2018 the Company further licensed Pan Am four additional immunotherapy products developed by the Company. These four patent-pending technologies are Cancer Metabolic Detox, MemoryMune, LymphoBoost, and innaMune.
We hope to develop new products that can be used together to attack cancer as different levels, as well as be used alone or in combination with existing therapies. The overarching approach to cancer is as follows:
The overarching approach to cancer on the StemVacs Platform is as follows:
Treat innate immune suppression: Administration of oral NanoStilbene to decrease immune suppressive toxic molecules made by tumor and tumor microenvironment.
Treat adaptive immune suppression: Administration of MemoryMune to activate dormant memory cells recognizing the tumor. Administration of LymphoBoost to repair deficient IL-12 production.
Stimulation of immune response to cancer stem cells (StemVacs).
Consolidation and maintenance of immunity: Cycles of StemVacs, supported by innaMune and LymphoBoost.
StemVacs
: StemVacs is a subcutaneously administered vaccine comprised of immune stimulatory peptides resembling cancer stem cell specific proteins.
StemVacs
is now available as a treatment option at the Pan American Cancer Treatment Center in Tijuana, Mexico for stages 1-4 breast and prostate cancers.
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.
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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.
Clinical Programs, Vaccines and Adjuvants
NanoStilbene Clinical Study in Cancer
1)
Pharmacokinetics of blood serum concentration across a prescribed period of time. This involves the study of the bodily absorption, distribution, metabolism, and excretion of drugs and the characteristic interactions of a drug and the body in terms of its absorption, distribution, metabolism, and excretion. This has been completed as of this writing.
2)
A small pilot study is in the planning stages to be performed under the direction of Dr. Santosh Kesari at John Wayne Cancer Institute in Santa Monica CA. by conducting a clinical trial assessing the effects of pterostilbene in modulating immune response and inflammatory parameters in a group of advanced solid tumor cancer patients. This has been completed as of this writing.
3)
Publication by Dr. Kesari, Dr. Ichim and other members of our team. This is currently underway.
NanoStilbene Clinical Study in Heart Disease
1)
A small pilot study is in the planning stages to be performed under the direction of Dr. Nassir Azimi in San Diego CA. by conducting a study using NanoStilbene in a group of heart attack patients.
2)
Publication by Dr. Azimi, Dr. Guzman, and other members of our team.
StemVacs Immunotherapy Platform for Prostate Cancer
StemVacs
is a platform for antigen-nonspecific immune modulatory treatment that can be utilized as a monotherapy or as a combination with antigen-specific modalities such as peptide or protein-based vaccines.
StemVacs
is, therefore, a subcutaneously administered vaccine comprised of immune stimulatory peptides resembling cancer stem cell-specific proteins.
StemVacs
is now available as a treatment option at the Pan American Cancer Treatment Center in Tijuana, Mexico for stages 1-4 breast and prostate cancers.
Immunotherapy as an Alternative to Watchful Waiting
Early Stage Prostate Cancer: Because prostate cancer often grows very slowly, some men (especially those who are older or have other serious health problems) might never need treatment for their prostate cancer. Instead, their doctors usually recommend approaches known as watchful waiting. If you have elevated PSA but slow-growing prostate cancer, does it make sense to play “Russian Roulette” with your health? Currently, the only medical intervention that is available to patients with early-stage prostate cancer who do not want to “wait” is taking
finasteride
, which although has been shown to decrease the overall incidence, the patients that developed aggressive cancer had higher aggression when taking finasteride as compared to controls.
Immunotherapy Instead of Waiting: One promising treatment that we are developing and offering at the Pan Am Cancer Treatment Center, for patients who are “watchfully waiting” is the application of an immunotherapy that expects to specifically train the immune system to attack cancer.
Immunotherapy has been approved by the FDA for treatment of late-stage prostate cancer in the form of the cellular drug Provenge. This drug is comprised of a type of immune system cell, termed “dendritic cell” that is generated from the blood of patients.
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It has the capacity to activate other immune cells in the body to attack proteins found on prostate-derived cells. Since prostate cancer cells possess prostate proteins, the immune system of patients treated with Provenge begins attacking prostate cancer cells not only in the prostate but all throughout the body. One of the main reasons why Provenge is not utilized in the United States for early-stage prostate cancer is its high costs.
This is very unfortunate because in the early stages of prostate cancer the immune system of the patient is still relatively intact, thus offering a much higher chance of success.
With the advantage of 10 years of experience in cellular processing and manufacturing, as well as a partnership with Key Opinion Leaders in the area of dendritic cell therapy, the Pan Am Cancer Treatment Center offers a novel way of dealing with early-stage prostate cancer.
Instead of “watchful waiting” or taking drugs that potentially increase the possibility of developing aggressive tumors, we offer a prostate cancer immunotherapeutic based on the same scientific principles as Provenge except for increased efficacy and lower price.
Rationale for Immunotherapy: The immune system is an ever-vigilant defense against bacterial, viral and parasitic infections, as well as against cancer
7
. Early studies demonstrated that some cancer patients whose immune systems are activated as a result of bacterial infections undergo remissions. Importantly, patients who have a chronically low level of immune activity are characterized by staggeringly high incidence of cancer.
Further support for an active role of the immune system in protecting the body against cancer comes from recent clinical trials in which a class of immune system stimulatory drugs termed “checkpoint inhibitors” have achieved previously unheard-of results in cancers resistant to treatment such as advanced prostate cancer.
It is well recognized that various types of cancers possess an incrementally higher level of ability to suppress the immune system the more advanced the cancer is. For example, in prostate cancer patients, those possessing a higher Gleason score suffer from an increased suppression of immune function.
Accordingly, augmentation of anticancer responses by introducing immunotherapy earlier in the pathogenesis of cancer progression increases the probability of success.
Conclusion:
At present, the only options available for patients with early-stage prostate cancer is waiting or taking drugs that potentially could increase aggressiveness.
StemVacs Immunotherapy Platform for Breast Cancer
StemVacs
is a platform for antigen-nonspecific immune modulatory treatment that can be utilized as a monotherapy or as a combination with antigen-specific modalities such as peptide or protein-based vaccines.
StemVacs
is, therefore, a subcutaneously administered vaccine comprised of immune stimulatory peptides resembling cancer stem cell-specific proteins.
StemVacs
is now available as a treatment option at the Pan American Cancer Treatment Center in Tijuana, Mexico for stages 1-4 breast and prostate cancers.
BRS-001:
Cancer Stem Cell Targeted Immunotherapy
BRS-001
is a patent-pending cellular immunotherapy developed by scientists at Therapeutic Solutions International, Inc., a San Diego Biotechnology Company, which is available at the Pan Am Cancer Treatment Center in Tijuana Mexico to treat stages 1-4 in breast cancer.
BRS-001
activates the immune system to seek and destroy cancer stem cells, based on their expression of a protein named Brother of the Regulator of Imprinted Sites (BORIS). BRS-001 is generated using white blood cells of the patient, which are grown outside of the body to create dendritic cells. The patient’s own dendritic cells are treated in vitro with peptides derived from BORIS, and subsequently are injected back into the patient in order to program the immune response to kill cells that express the protein BORIS, which are cancer stem cells.
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Without Killing of Cancer Stem Cells, it is Impossible to Cure Cancer
All tumor cells are the offspring of a single, aberrant cell, but they are not all alike. Only a few retain the capacity of the original cell to create an entire tumor. Such cancer stem cells can migrate to other tissues and become fatal metastases. To fully cure a patient’s cancer, it is crucial to find and eliminate all of these cells because any that escape can regenerate the tumor and trigger its spread through the body.
BORIS is Essential for Cancer “To be Cancer”
The BORIS protein functions to disable a tumor suppressor termed “CTCF”. The role of CTCF is to ensure that parts of DNA that should not be activated, indeed are not activated. For example, one of the roles of CTCF is to block expression of genes that cause cancer. In cancer stem cells, BORIS blocks the function of CTCF, thus allowing for propagation of cancer. It has been shown that if BORIS is blocked in cancer stem cells, the cancer stem cells no longer form tumors.
BRS-001 is Selective Immunotherapy
Dendritic cells are the most potent immune stimulatory cell of the body. Currently, dendritic cell therapy is approved in the USA in the form of the drug Provenge. BRS-001 consists of dendritic cells that are treated with parts of the BORIS protein in order to stimulate killer T cell responses against any cell that expresses BORIS. Using dendritic cells to stimulate immunity offers the advantage of inducing immunological memory against the tumor. Published studies by us in collaboration with the NIH showed immunity to BORIS results in tumor killing.
Preclinical Proof
The BRS-001 construct is capable of stimulating immune responses that cross over to wild-type tumors without having the potential of causing cancer. This ability to induce tumor immunity was validated across a broad variety of tissue types making the BRS-001 approach broadly applicable for numerous cancers. This was described in peer-reviewed papers by Company scientists demonstrating that immunization with BRS-001 not only inhibits growth of aggressive breast cancer 4T1 cells in BALB/c mice, but also that mice immunized with BRS-001 contain high numbers of CD8+ T cells that have spontaneous cytolytic activity against breast, leukemia, and glioma cells in vitro.
The BRS-001 construct is capable of stimulating immune responses that crossover to wild-type tumors without having the potential of causing cancer. This ability to induce tumor immunity was validated across a broad variety of tissue types making the BRS-001 approach broadly applicable for numerous cancers.
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This was described in peer reviewed papers by Company scientists demonstrating that immunization with BRS-001 not only inhibits growth of aggressive breast cancer 4T1 cells in BALB/c mice, but also that mice immunized with BRS-001 contain high numbers of CD8+ T cells that have spontaneous cytolytic activity against breast, leukemia, and glioma cells invitro.
Company scientists have determined that vaccination with BRS-001 in the context of various immune stimulatory technologies induces a CD8 cytotoxic T cell response that recognizes tumors independent of tissue origin.
Conclusion:
This type of immune response is usually associated with remission of the tumor. Based on this mechanism of action, Therapeutic Solutions International, Inc. has decided to develop a dendritic cell BORIS-peptide pulsed candidate as the most promising method of stimulating immune responses to BORIS in cancer patients.
Additional StemVacs Platform Immunotherapeutics
NanoStilbene: Patented Augmenter of Cancer Immunotherapy
NanoStilbene
, a nanoparticle formulation of pterostilbene, is covered for use in cancer immunotherapy under the Company’s issued U.S. Patent No.: 9,682,047 and is included as part of the Prostate and Breast Cancer Protocol with StemVacs.
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NanoStilbene
is an easily absorbed nanoemulsion of nanoparticle pterostilbene in the range of 75-100nm at a concentration of 30 milligrams per milliliter. The pterostilbene placed in a nanoemulsion droplet is free from air, light, and hard environment; therefore, as a delivery system, nanoemulsion can not only improve the bioavailability of pterostilbene but also protect it from oxidation and hydrolysis, while it possesses an ability of sustained release at the same time.
Therapeutic uses of nanotechnology typically involve the delivery of small-molecule drugs, peptides, proteins, and nucleic acids. Nanoparticles have advanced pharmacological effects compared with the therapeutic entities they contain. Active intracellular delivery and improved pharmacokinetics and pharmacodynamics of drug nanoparticles depend on various factors, including their size and surface properties.
Nanoparticle therapeutics is an emerging treatment modality in cancer and other inflammatory disorders. The National Cancer Institute has recognized nanotechnology as an emerging field with the potential to revolutionize modern medicine for detection, treatment, and prevention of cancer.
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.
Patent Title: Targeting the Tumor Microenvironment through Nutraceutical Based Immunoadjuvants
Disclosed are 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.
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.
Patent Title: Activated Leukocyte Extract for Repair of Innate Immunity in Cancer Patients
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.
LymphoBoost:
LymphoBoost is a proprietary formulation of Mifepristone, 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.
Augmentation of Anti-Tumor Immunity by Mifepristone and Analogues Thereof
The present invention 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.
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”.
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Patent Title: Methods of Re-Activating Dormant Memory Cells with Anticancer Activity
Disclosed are 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.
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.
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.
There have been no material changes to the critical accounting policies as previously disclosed in our Annual Report on Form 10-K for the year ended December 31, 2017, which was filed with the SEC on April 17, 2018.
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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 cure 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.
Nutraceutical Division
– TSI has been producing high quality nutraceuticals. Its flagship product, ProJuvenol
®
, is a proprietary mixture containing pterostilbene – one of the most potent antioxidants known. TSOI was granted U.S. Patent No.: 9,682,047 for ProJuvenol
®
on 06-20-2017.
For the three and nine months ended September 30, 2018 and 2017
Prepaid expenses and other current assets increased $180,724, from $1,054 to $181,778 as of September 30, 2017 and 2018, respectively. This increase was mainly due to an increase in consulting agreements and scientific board member agreements that were entered into during the nine months ended September 30, 2018. These agreements are capitalized over the number of months of their respective agreements.
We had a net loss of $167,774 for the three months ended September 30, 2018, compared to a net loss of $266,763 for the three months ended September 30, 2017, a decrease of $98,989. This decrease was mainly due to increases in consulting fees, loss on derivative liability, interest expense, a decrease in legal and professional fees and changes in fair value of derivatives liabilities. We had a net loss of $1,058,465 for the nine months ended September 30, 2018, compared to a net loss of $700,573 for the nine months ended September 30, 2017, an increase of $357,892. This increase was mainly due to increases in salaries, wages and related costs, consulting fees, research and development, loss on derivative liability, interest expense, a decrease in legal and professional fees, and changes in fair value of derivatives liabilities.
Net sales increased $2,671, from $630 to $3,301, for the three months ended September 30, 2017 and September 30, 2018, respectively. Net sales increased $2,997, from $1,923 to $4,920, for the nine months ended September 30, 2017 and September 30, 2018, respectively.
Cost of goods sold increased $369, from $191 to $560, for the three months ended September 30, 2017 and September 30, 2018, respectively. Cost of goods sold increased $153, from $616 to $769, for the nine months ended September 30, 2017 and September 30, 2018, respectively. These increases were mainly increases in net sales for products in 2018 and 2017.
Operating expenses for the three month periods ended September 30, 2018 and 2017 were $259,336 and $208,156, an increase of $51,180. This increase was mainly due to an increase in salaries, wages, and related costs, consulting fees, research and development, and a decrease in legal and professional fees. Operating expenses for the nine month periods ended September 30, 2018 and 2017 were $693,863 and $628,522, an increase of $65,342. This increase was mainly due to increases in salaries, wages and related costs, consulting fees, research and development, coupled with a decrease in legal and professional fees.
General and administrative expenses decreased $1,979, from $22,694 to $20,715, for the three months ended September 30, 2017 and 2018, respectively. This decrease was mainly due to decreased continuing education expense in the comparable quarters in 2018 compared to 2017. General and administrative expenses decreased $18,484, from $75,437 to $56,953, for the nine months ended September 30, 2017 and 2018, respectively. This decrease was mainly due decreased bad debt expense in the comparable quarters in 2018 compared to 2017.
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Salaries, wages and related costs increased $14,578, from $95,536 to $110,114 for the three months ended September 30, 2017 and 2018, respectively. This increase was mainly due to an increase in wage related expenses. Salaries, wages and related costs increased $29,925, from $279,838 to $309,763 for the nine months ended September 30, 2017 and 2018, respectively. This increase was mainly due to an increase in wage related expenses.
Selling expenses decreased $119, from $712 to $593, for the three months ended September 30, 2017 and 2018, respectively. This was mainly due a decrease in selling and marketing expenses related to the Company’s products during the period. Selling expenses decreased $767, from $2,538 to $1,771, for the nine months ended September 30, 2017 and 2018, respectively. This was mainly due a decrease in selling and marketing expenses related to the Company’s products during the period.
Consulting fees increased $28,396 from $22,950 to $51,346 for the three months ended September 30, 2017 and 2018, respectively, due to an increase in overall consulting services. Consulting fees increased $51,067 from $29,650 to $80,717 for the nine months ended September 30, 2017 and 2018, respectively, due to an increase in overall consulting services.
Legal and professional fees decreased $21,554, from $64,226 to $42,672 for the three months ended September 30, 2017 and September 30, 2018, respectively, due to a decrease in legal expenses. Legal and professional fees decreased $46,046, from $216,945 to $170,899 for the nine months ended September 30, 2017 and September 30, 2018, respectively, due to a decrease in legal expenses.
Research and development costs increased $31,858, from $2,038 to $33,896, for the three months ended September 30, 2017 and 2018, respectively. This increase was mainly due to increased research and development expenses related our NanoStilbene products for the comparable three month periods. Research and development costs increased $49,616, from $24,144 to $73,760, for the nine months ended September 30, 2017 and 2018, respectively. This increase was mainly due to increased research and development expenses for the comparable nine month periods.
Loss on derivatives liability increased $55,253, from $83,968 to $139,221 for the three months ended September 30, 2017 and September 30, 2018, respectively. This increase was due to a derivative liability loss from additional convertible notes outstanding at September 30, 2018 compared to September 30, 2017. Loss on derivatives liability increased $176,708, from $83,968 to $260,676 for the nine months ended September 30, 2017 and September 30, 2018, respectively. This increase was due to a derivative liability loss from certain convertible notes at September 30, 2018 compared to September 30, 2017.
Change in fair value of derivative liabilities increased $264,163 from $35,285 to $299,448 for the three months ended September 30, 2017 and September 30, 2018, respectively. This increase was due to a derivative liability revaluation change from all outstanding convertible notes for the three months ended September 30, 2018 compared to September 30, 2017. Change in fair value of derivative liabilities increased $17,067 from $35,285 to $52,352 for the nine months ended September 30, 2017 and September 30, 2018, respectively. This increase was due to a derivative liability revaluation change from all outstanding convertible notes for the nine months ended September 30, 2018 compared to September 30, 2017.
Net interest expense increased $61,043 from $10,363 to $71,406 for the three months ended September 30, 2017 and September 30, 2018, respectively. This increase was mainly due to increased debt balances. Net interest expense increased $135,754 from $24,675 to $160,429 for the nine months ended September 30, 2017 and September 30, 2018, 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 $6.3 million and a working capital deficit of approximately $1.5 million at September 30, 2018. These conditions raise significant doubt about the Company’s ability to continue as a going concern for the 12 months subsequent to the issuance of the September 30, 2018 financial statements. 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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