Compositions and methods for treating and preventing neurodegenerative and / or neuropsychiatric conditions, cancer, and other

Abstract

Pharmaceutical compositions that include a benzimidazole, benzimidazole derivative, or a metabolite thereof and a selenium source, and their use in methods for the treatment or prevention of an indication selected from, Alzheimer's disease, Parkinson's disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, or cancer in a subject are described herein.

Description

PCT / US25 / 44424 02 September 2025 (02.09.2025)COMPOSITIONS AND METHODS FOR TREATING AND PREVENTING ALZHEIMER’S DISEASE, PARKINSON’S DISEASE, FRONTOTEMPORAL DEMENTIA, FRONTOTEMPORAL LOBAR DEGENERATION, DEMENTIA, COGNITIVE DECLINE COGNITIVE DECLINE, NEURAL INJURIES, NEURODEGENERATION, AND / OR NEURODEGENERATIVE AND / OR NEUROPSYCHIATRIC CONDITIONS, NEURODEGENERATIVE AND / OR NEUROPSYCHIATRIC DISEASES, AND / OR NEURODEGENERATIVE AND / OR NEUROPSYCHIATRIC DISORDERS, CANCER, AND OTHERRELATED APPLICATION

[0001] This application claims priority from U.S. Provisional Application Nos. 63 / 692,034, filed September 7th, 2024; and 63 / 707,731, filed October 15th, 2024, as well as from International Application (PCT) Nos.: PCT / US25 / 43245, filed August 22, 2025; and PCT / US25 / 44157, filed August 29, 2025, the subject matter of which are incorporated herein by reference in their entirety.TECHNICAL FIELD

[0002] The present disclosure relates to novel compositions of matter and novel methods to treat various medical indications including Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, dementia, cognitive decline, neural injuries, neurodegeneration, and / or neurodegenerative and / or neuropsychiatric conditions, neurodegenerative and / or neuropsychiatric diseases, and / or neurodegenerative and / or neuropsychiatric disorders and cancer.BACKGROUND

[0003] As of yet, despite a plethora of government and private industry participants massively investing for decades into discovering a viable treatment for the indications, none have proposed a satisfactory treatment for the indications or a treatment that has been widely accepted or that has actually cured any of the indications, including Alzheimer’s disease(s), Parkinson’s disease(s), Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), frontotemporal lobe dementia, other dementia diseases, cognitive decline, and alsoPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 related diseases and / or indications such as dementia related vision degeneration and / or loss, dementia related hearing degeneration and / or loss, dementia related olfactory dysfunction including loss and / or degeneration of the sense of smell, dementia induced postural stoop, dementia induced loss and / or degeneration of motor coordination and the ability to normally walk and rise from a seated position, and other. It is an object of the present disclosure to provide treatment for the indications and for these diseases and / or conditions as well as compositions for treating the indications and these diseases and / or conditions.

[0004] Therefore, it readily can be appreciated that despite the massive investment for decades of a plethora of government and industry participants that a long-felt need continues to exist for an effective treatment for the indications, including but not limited to dementia including but not limited to Alzheimer’s disease and other dementias, cognitive decline, Parkinson’s, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), and frontotemporal lobe dementia.

[0005] Accordingly, it follows that any treatment for any form of dementia for which a successful treatment has not yet been discovered is not an obvious discovery and / or invention.

[0006] While various compositions of matter and methods of use of matter and methods of treatment exist for various conditions and diseases, as of yet none have proposed either the treatments proposed by the present disclosure or the compositions of matter, methods of use of substances; and / or methods for treating the indications that is proposed and taught by the present disclosure.SUMMARY

[0007] Embodiments described herein relate to pharmaceutical compositions for the treatment or prevention of an indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, or for the treatment or prevention of cancer, wherein the pharmaceutical compositions include a benzimidazole, benzimidazole derivative, or a metabolite thereof in combination with a selenium source, as well as their use in methods of treating or preventing an indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, and / or cancer in a subject in need thereof using pharmaceutical compositions that include a benzimidazole, benzimidazole derivative, or a metabolite thereof, a selenium source, and optionally praziquantel. Compositions and methods described herein are based, in part, on the discovery of the therapeutically effective doses and dosing regimens of a benzimidazole, a selenium source, and optionally praziquantel, wherein the doses and dosing regimens far exceed the normal or recommended regimen or frequency and total dose and / or dosing regimens of the agents administered over a period of time.

[0008] An embodiment described herein relates to a pharmaceutical composition for the treatment of an indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FID) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, and / or cancer. The pharmaceutical composition includes a benzimidazole, benzimidazole derivative, or a metabolite thereof, and a selenium source. In some embodiments, the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, flubendazole, ciclobendazole, thiabendazole, and combinations thereof. In some embodiments, the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, and combinations thereof. In some embodiments, the benzimidazole includes fenbendazole.

[0009] In some embodiments, the selenium source is a source of bioavailable selenium. The selenium source can include a bioavailable selenium source selected from the group consisting of selenomethionine, selenocystine, sodium selenite, sodium selenate, methylselenocysteine, selenium glycinate, and a selenium nanoparticle. In some embodiments, the selenium source includes L-selenomethionine.

[0010] In some embodiments, the composition further includes praziquantel.

[0011] In some embodiments, the composition further includes a pharmaceutically acceptable carrier. In some embodiments, the composition is formulated as an oral dosage form. The oral dosage form can include a suspension.

[0012] In some embodiments, the composition includes at least 2000 mg of the benzimidazole. In other embodiments, the composition includes at least 4000 mg of the benzimidazole. In some embodiments, the benzimidazole is fenbendazole.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3

[0013] In some embodiments, the composition includes at least 800 mg of praziquantel. In other embodiments, the composition includes at least 1600 mg of praziquantel.

[0014] Additional embodiments relate to a method of treating or preventing Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, and / or cancer in a subject in need thereof. The method includes administering to the subject a therapeutically effective amount of a pharmaceutical composition. The pharmaceutical composition includes a benzimidazole, benzimidazole derivative, or a metabolite thereof. The pharmaceutical composition also includes a selenium source and a pharmaceutically acceptable carrier.

[0015] In some embodiments, the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, flubendazole, ciclobendazole, thiabendazole, and combinations thereof. In some embodiments, the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, and combinations thereof. In some embodiments, the benzimidazole includes fenbendazole.

[0016] In some embodiments, the selenium source is a source of bioavailable selenium. In some embodiments, the selenium source is a source of bioavailable selenium selected from the group consisting of selenomethionine, selenocystine, selenite, selenate, methylselenocysteine, selenium glycinate and a selenium nanoparticle. In some embodiments, the selenium source includes L-selenomethionine.

[0017] In some embodiments, the indication is cognitive decline, dementia, Parkinson’s disease or Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD). In some embodiments, the cancer is a solid tumor type cancer. In some embodiments, the cancer is breast cancer, lung cancer, prostate cancer, pancreatic cancer, cancers of the brain, brain tumors, brain cancer and other nervous system cancer, esophageal cancer, liver cancer and / or intrahepatic bile duct cancer, acute myeloid leukemia, stomach cancer, myeloma, laryngeal cancer, anaplastic thyroid cancer, colorectal cancer, Non- Hodgkin Lymphoma, or ovarian cancer.

[0018] In some embodiments, the dementia is Alzheimer’s disease. In some embodiments, the therapeutically effective amount is the amount required to ameliorate at least one symptom of the indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder. In some embodiments, the cancer is selected from the group consisting of non-small cell lung cancer (NSCLC), melanoma, cervical cancer, colorectal cancer, leukemia, hepatocellular carcinoma, estrogen receptor positive (ER+) breast cancer and triple negative breast cancer (TNBC). In some embodiments, the therapeutically effective amount is the amount required to ameliorate at least one symptom of the cancer. In some embodiments, the therapeutically effective amount is the amount required to ameliorate at least a majority of and / or all symptoms of the indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder. In some embodiments, the subject is treated until resolution of the indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder. In some embodiments, the therapeutically effective amount is the amount required to ameliorate at least a majority of symptoms of the cancer and / or all symptoms of the cancer. In some embodiments, the subject is treated until resolution of the cancer.

[0019] In some embodiments, the method further includes the step of administering a maintenance amount of the pharmaceutical composition to the subject to prevent relapse of the cancer. In some embodiments, the maintenance amount of fenbendazole is from about 100 mg to about 1000 mg daily. In some embodiments, the maintenance amount of the selenium source is sufficient to provide an assimilable form of selenium that includes from about 50 mcg to about 1750 mcg of elemental selenium daily or every other day. In some embodiments, the therapeutically effective amount of the selenium source in the composition administered to the subject is the amount required to reduce toxicity of the benzimidazole, benzimidazole derivative, or a metabolite thereof, to non-cancerous cells of the subject. The non-cancerous cells can include hepatocytes.

[0020] In some embodiments, the pharmaceutical composition is formulated as an oral dosage form. In some embodiments, the oral dosage form comprises a suspension.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3

[0021] In some embodiments, the subject is a human.

[0022] In some embodiments of the method, from about 400 mg to 20,000 mg, about 2,800 mg to 10,000 mg, about 2,800 mg to 5,200 mg, or about 4,500 mg to 5,200 mg of the benzimidazole is administered daily or every other day. In some embodiments, the benzimidazole is fenbendazole.

[0023] In some embodiments, from about 250 mcg to about 10 mg, about 600 mcg to about 7.5mg, or about 1200mcg to about 7.0 mg of bioavailable elemental selenium is administered daily or every other day.

[0024] In some embodiments, the pharmaceutical composition further includes praziquantel. In some embodiments, at least 800 mg or at least 1600 mg of praziquantel is administered or every other day.

[0025] In other embodiments where the pharmaceutical composition further includes praziquantel, at least 100 mg or at least 400 mg of praziquantel is administered or every other day and / or every other dose.

[0026] In some embodiments, the dose of praziquantel is about 800 mg. In some embodiments, the dose of praziquantel is administered daily or every other day.

[0027] In some embodiments, a dose of elemental selenium is in a range of from about 250 mcg to about 10 mg of bioavailable elemental selenium. In some embodiments, the dose of elemental selenium is administered daily or every other day.

[0028] In some embodiments, a dose of fenbendazole is in a range of from about 400 mg to about 5,000 mg. In some embodiments, the dose of fenbendazole is administered daily or every other day.

[0029] In some embodiments, the method further includes administration of at least one vehicle so as to improve the solubility of a benzimidazole, benzimidazole derivative, or a metabolite thereof or composition thereof when administered to a subject.BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The following is a brief description of the drawings which are presented for the purpose of illustrating the invention and not for the purpose of limiting them.

[0031] Fig. 1 is a flow diagram illustrating an example method for treating an indication, disease, disorder, or condition in accordance with an embodiment described herein including administering to a subject in need thereof a benzimidazole in combination with a selenium source and further optionally in combination with praziquantel and / or further administering a maintenance amount of the benzimidazole and of the selenium source and optionally praziquantel to the subject.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3

[0032] Fig. 2 is a flow diagram illustrating an example method for treating an indication, disease, disorder, or condition in accordance with an embodiment described herein including administering to a subject in need thereof a therapeutically effective amount of benzimidazole and of a source of bioavailable selenium at the same time and optionally including the step of administering a therapeutically effective amount of praziquantel and / or further administering a maintenance amount of the benzimidazole and of the source of bioavailable selenium and optionally praziquantel to the subject.

[0033] Fig. 3 is a flow diagram illustrating an example method for preventing cognitive decline symptoms from manifesting to a level where they are diagnosable as cognitive decline including administering to a subject in need thereof a benzimidazole in combination with a source of bioavailable selenium and optionally including the step of administering to the subject praziquantel.

[0034] Fig. 4 is a flow diagram illustrating an example method for treating cancer in a subject including administering to a subject in need thereof a benzimidazole in combination with a source of bioavailable selenium and optionally including the step of administering to the subject praziquantel.DETAILED DESCRIPTIONDefinitions

[0035] All scientific and technical terms used in this application have meanings commonly used in the art unless otherwise specified. The definitions provided herein are to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the application.

[0036] The articles "a" and "an" are used herein to refer to one or to more than one (z.e., to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0037] The terms "comprise," "comprising," "include," "including," "have," and "having" are used in the inclusive, open sense, meaning that additional elements may be included. The terms "such as", "e.g., ", as used herein are non-limiting and are for illustrative purposes only. "Including" and "including but not limited to" are used interchangeably.

[0038] The verb “comprise” as is used in this description and in the claims and its conjugations are used in its non-limiting sense to mean that items following the word arePCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 included, but items not specifically mentioned are not excluded. The present invention may suitably “comprise”, “consist of’, or “consist essentially of’, the steps, elements, and / or reagents described in the claims.

[0039] It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as "solely", "only" and the like in connection with the recitation of claim elements, or the use of a "negative" limitation.

[0040] Throughout the description, where compositions are described as having, including, or comprising, specific components, it is contemplated that compositions also consist essentially of, or consist of, the recited components. Similarly, where methods or processes are described as having, including, or comprising specific process steps, the processes also consist essentially of, or consist of, the recited processing steps. Further, it should be understood that the order of steps or order for performing certain actions is immaterial so long as the compositions and methods described herein remains operable. Moreover, two or more steps or actions can be conducted simultaneously.

[0041] The term “pharmaceutically acceptable” means suitable for use in contact with the tissues of humans and animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio, and effective for their intended use within the scope of sound medical judgment.

[0042] The phrases “enteral administration” and “administered enterally” are art- recognized terms, and include modes of administration involving the gastrointestinal tract, and include without limitation, oral administration, gastric administration (e.g., through the use of nasogastric tubes and percutaneous endoscopic gastronomy tubes), rectal administration, and jejunal administration (e.g., through ajejunostomy tube).

[0043] The phrases "parenteral administration" and "administered parenterally" are art- recognized terms, and include modes of administration other than enteral and topical administration, such as injections, and include, without limitation, intravenous, intramuscular, intrapleural, intravascular, intrapericardial, intraarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intraarticular, subcapsular, subarachnoid, intraspinal and intrastemal injection and infusion.

[0044] The terms "treating", “treatment” and “to treat” are art-recognized and includes inhibiting an indication, disease, disorder or condition in a subject, e.g., impeding its progress; and relieving the indication, disease, disorder or condition, e.g., causing regression of the disease, disorder and / or condition. Treating the indication, disease, disorder, orPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 condition may include ameliorating at least one symptom of the particular indication, disease or condition, even if the underlying pathophysiology is not affected. In some embodiments, the terms “treating” and “treatment” and “to treat” may also include the terms “curing” and “cure” and “to cure”.The term "preventing" is art-recognized and includes stopping an indication, disease, disorder or condition from occurring in a subject, which may be predisposed to the disease, disorder and / or condition but has not yet been diagnosed as having it. Preventing a condition related to a disease includes stopping the indication, disease, or condition from occurring after the indication, disease, or condition has been diagnosed but before the the indication, disease, or condition has been diagnosed.

[0045] A "patient," "subject," or "host" to be treated by the subject method may mean either a human or non-human animal, such as a mammal, a fish, a bird, a reptile, or an amphibian. Thus, the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig or rodent. The term does not denote a particular age or sex. Thus, adult and newborn subjects, as well as fetuses, whether male or female, are intended to be covered. In one aspect, the subject is a mammal. A patient refers to a subject afflicted with an indication, disease or disorder. In one aspect the patient is an adult human subject who is an occasional or daily smoker. In another aspect, the patient is a patient with compromised liver function.

[0046] The terms "prophylactic” or “therapeutic" treatment is art-recognized and includes administration to the subject of one or more of the subject compositions. If it is administered prior to clinical manifestation of the unwanted indication or condition (e.g., disease or other unwanted state of the subject) then the treatment is prophylactic, i.e., it protects the subject against developing the unwanted indication, disease or condition, whereas if it is administered after manifestation of the unwanted indication, disease or condition, the treatment is therapeutic (i.e., it is intended to diminish, ameliorate, or stabilize the existing unwanted indication, disease or condition or side effect(s) thereof).

[0047] The terms "therapeutic agent", "drug", "medicament" and "bioactive substance" are art-recognized and include a chemical compound, a mixture of chemical compounds, and other agents that are biologically, physiologically, or pharmacologically active substances that act locally or systemically in a patient or subject to treat an indication, disease, disorder or condition. The terms include without limitation pharmaceutically acceptable salts thereof and prodrugs. Such agents may be acidic, basic, or salts; they may be neutral molecules, polar molecules, or molecular complexes capable of hydrogen bonding; they may be prodrugs in the form of ethers, esters, amides and the like that are biologically activated whenPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 administered into a patient or subject.

[0048] The phrase "therapeutically effective amount" or “pharmaceutically effective amount” is an art-recognized term. In certain embodiments, the term refers to an amount of a therapeutic agent, or combination of therapeutic agents, that produces some desired effect at a reasonable benefit / risk ratio applicable to any medical treatment. In certain embodiments, the term refers to that amount necessary or sufficient to eliminate, reduce or maintain a target of a particular therapeutic regimen. The effective amount may vary depending on such factors as the indication, disease or condition being treated, the particular combination of agents and formulation thereof being administered, the size of the subject or the severity of the indication, disease or condition. One of ordinary skill in the art may empirically determine the effective amount of a particular compound or combination of agents / compounds without necessitating undue experimentation. In certain embodiments, a therapeutically effective amount of therapeutic agents(s) for in vivo use will likely depend on a number of factors, including: the rate of release of an agent from a pharmaceutically acceptable carrier, such as a polymer matrix, which will depend in part on the chemical and physical characteristics of the polymer; the identity of the agent(s); the mode and method of administration; and any other materials incorporated in the formulation in addition to the agent.

[0049] "Optional" or "optionally" means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not. For example, the phrase "optionally administered" means that a particular therapeutic agent, e.g., praziquantel may or may not be included in a pharmaceutical composition, and, thus, the description includes pharmaceutical compositions and therapeutic uses thereof wherein praziquantel is present and pharmaceutical compositions and therapeutic uses thereof wherein praziquantel is not present.

[0050] The term "or" as used herein should be understood to mean "and / or", unless the context clearly indicates otherwise. As used herein, the term “and / or” and the symbol “ / ” are meant to include any and all combinations of one or more of the associated listed items.

[0051] As used herein, the term "about" or "approximately" refers to a quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length that varies by as much as 15%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2% or 1% to a reference quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length. In one embodiment, the term "about" or "approximately" refers a range of quantity, level, value, number, frequency, percentage, dimension, size, amount, weight or length ± 15%, ± 10%, ± 9%, ± 8%, ± 7%, + 6%, ± 5%, ± 4%, ± 3%, ± 2%, or + 1% about a reference quantity, level,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 value, number, frequency, percentage, dimension, size, amount, weight or length.

[0052] All percentages and ratios used herein, unless otherwise indicated, are by weight.

[0053] The terms "healthy" and "normal" are used interchangeably herein to refer to a subject or particular cell or tissue that is devoid (at least to the limit of detection) of an indication, disease or condition.

[0054] The terms “indication”, "disease", "disorder", or “condition” are used interchangeably herein, and refer to any alteration in state of the body or of some of the organs, interrupting or disturbing the performance of the functions and / or causing symptoms such as discomfort, dysfunction, distress, or even death to the person afflicted or those in contact with a person. An indication, disease, disorder or condition can also relate to a distemper, ailing, ailment, malady, disorder, sickness, illness, complaint, or affectation. In some embodiments, indications shall include without limitation cognitive decline, neural injuries, neurodegenerations, and / or neurodegenerative and / or neuropsychiatric conditions, diseases, and / or disorders.

[0055] An object and an effect of the present invention may be naturally understood or may become clearer from the following description, and the object and the effect of the present invention are not restricted only by the following description. In addition, in the description of the present invention, the specific descriptions of publicly known technologies that relate with the present invention will be omitted when it is determined that the specific descriptions may unnecessarily obscure the subject matter of the present invention.

[0056] Embodiments described herein relate generally to pharmaceutical compositions including a benzimidazole, benzimidazole derivative, or a metabolite thereof, in combination with a selenium source. Additional embodiments relate broadly to methods of treating cognitive decline, neural injuries, neurodegeneration, and / or neurodegenerative and / or neuropsychiatric conditions, diseases, and / or disorders in a subject in need thereof using pharmaceutical compositions including a benzimidazole, benzimidazole derivative, or a metabolite thereof.

[0057] The present disclosure is based upon the surprising and unexpected discovery that indications including dementia and dementia related conditions and / or diseases such as indications including cognitive decline, Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTED), Parkinson’s disease and drug / chemical injury induced Parkinson’s disease (DIP), especially early and middle stages of these diseases, are able to be ameliorated, inhibited, arrested, reversed, cured and / or resolved, by a therapeuticPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 treatment course that comprises administration of the benzimidazole compound fenbendazole in combination with the selenium source L-selenomethionine, especially without becoming toxic to the subject treated.

[0058] In more detail, the present disclosure is based upon the surprising and shocking discovery that indications including dementia and dementia related conditions and / or diseases such as indications including cognitive decline, Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease and drug / chemical injury induced Parkinson’s disease (DIP), especially early and middle stages of these diseases, are able to be effectively ameliorated, inhibited, arrested, reversed, cured and / or resolved by a therapeutic treatment course that comprises administration of what we propose would be considered megadoses and megadosages of a the benzimidazole compound fenbendazole as well as what we propose would be considered megadoses and megadosages of the selenium source L-selenomethionine, especially without becoming toxic to the subject treated.

[0059] The term “megadose”, as used herein, refers to a dose of a therapeutic agent, such as a drug or vitamin, that is administered to a subject intentionally and that far exceeds the normal or recommended amount. In general, a megadose generally refers to a dose many times higher than the recommended daily allowance (RDA). In particular embodiments, a megadose of a therapeutic agent (e.g., a drug or nutritional supplement) is a dose quantity that exceeds the Recommended Daily Amount (RDA) or Acceptable Daily Intake (ADI) by a factor of 10 or more. The broader term, “megadosage”, as used herein, can refer to a dosage of a therapeutic agent, such as a drug or vitamin, that is administered to a subject intentionally and that far exceeds the normal or recommended regimen or frequency and total dose of the agent administered over a period of time.

[0060] It has further surprisingly and shockingly been found that a treatment comprising administration of all of: the megadoses and megadosages of fenbendazole; the megadoses and megadosages of the L-selenomethionine; and, the antiparasitic agent praziquantel, is efficacious at treating indications including cognitive decline, Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease and drug / chemical injury induced Parkinson’s disease (DIP), especially early and middle stages of these diseases.

[0061] Therefore, in other embodiments of the present disclosure, a therapeutic treatment course that includes the administration of both a benzimidazole, benzimidazole derivative, or a metabolite thereof (e.g., fenbendazole) and a selenium source (e.g., L-PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 selenomethionine) further comprises administration of the antiparasitic agent praziquantel. In this case we propose that the administration of a megadosage of praziquantel is optimally administered for a duration of time and at a quantity of doses that we propose should be considered a very long and unusually lengthy treatment course of praziquantel with an unusually high number of dosing events that far exceeds the normal or recommended dosage used for routine antiparasitic treatment in a mammal.Therapeutic Agents

[0062] A benzimidazole, benzimidazole derivative or metabolite thereof for use in compositions and methods described herein can include fenbendazole, mebendazole, albendazole, flubendazole, ciclobendazole, thiabendazole. In some embodiments, a combination of one or more benzimidazoles, benzimidazole derivatives or metabolites thereof can be used in a composition or method described herein.

[0063] In some useful embodiments, the benzimidazole includes fenbendazole, mebendazole, albendazole, or combinations thereof. For example, in particular embodiments, the benzimidazole is fenbendazole, mebendazole, and then albendazole, in that order. In highly useful embodiments, the benzimidazole is fenbendazole.

[0064] In some embodiments, one or more benzimidiazole metabolites and / or benzimidiazole derivative metabolites can be used in compositions or method described herein. In certain embodiments, metabolites of fenbendazole can include, but are not limited to, fenbendazole sulfone and / or fenbendazole sulfoxide, as empirically able to be determined useful.

[0065] In all embodiments of the present disclosure, it is disclosed that the fenbendazole may be substituted by another benzimidazole, benzimidazole derivative, or metabolites thereof and / or by a combination of any benzimidazoles, benzimidazole derivatives, and metabolites thereof, however, our experiments in vitro comparing subject and human patient outcomes when using and administering other benzimidazoles in substitution of fenbendazole (e.g. mebendazole, albendazole) have shown that superior efficacy and superior overall outcomes (and in fact dramatically superior efficacy and dramatically superior overall outcomes) are achieved when using fenbendazole as disclosed in the present disclosure in comparison to using and / or substituting another benzimidazole and / or combination of other benzimidazoles in place of fenbendazole, including dramatically superior efficacy and dramatically superior outcomes for human patients. Nonetheless, in recognition of the fact that clinical studies with dozens or hundreds of human patients should be undertaken and concluded in order to make a final determination as to whether or notPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 substituting any other benzimidazole, benzimidazole derivative, or metabolites thereof and / or combination of other benzimidazoles, benzimidazole derivative, or metabolites thereof in place of fenbendazole for all teachings and disclosures of the present disclosure pertaining to fenbendazole truly yield unsatisfactory and / or less satisfactory outcomes and / or lesser efficacy and / or safety in comparison to fenbendazole for all teachings and disclosures of the present disclosure pertaining to fenbendazole, the present disclosure discloses using, for example, another benzimidazole (including but not limited to mebendazole, albendazole, flubendazole, ciclobendazole, thiabendazole) and / or combination of benzimidazoles in substitution of fenbendazole, for any and all teachings of the present disclosure that pertain to fenbendazole and the present disclosure discloses further embodiments wherein the term “fenbendazole” as used in the present disclosure may be substituted by any other benzimidazole (including but not limited to mebendazole, albendazole, flubendazole, ciclobendazole, thiabendazole) and / or combination of benzimidazoles, and / or benzimidazole derivatives, and / or metabolites thereof for any and all teachings and / or disclosures of the present disclosure pertaining to fenbendazole, however, such embodiments are not presently experimentally confirmed as both useful and exhibiting acceptable toxicity when used to formulate compositions of the present disclosure or when used as substances and / or agents of methods of the present disclosure for purposes of the present disclosure, whereas fenbendazole is confirmed as useful and exhibiting acceptable toxicity and / or no toxicity for purposes of the present disclosure including when used to formulate compositions of the present disclosure or when used as substances and / or agents of methods of the present disclosure for purposes of the present disclosure, and experiments should be conducted to determine if any other benzimidazole, benzimidazole derivative, or metabolites thereof, are as suitable or more suitable in comparison to fenbendazole for purposes of the present disclosure. It is noted that the use of fenbendazole as disclosed in the present disclosure, and especially the use of disclosed confirmed useful doses, dosages and megadoses and megadosages of fenbendazole is contrary to the state of the art, against the trend in the field, and against the widely held beliefs of those skilled in the art.

[0066] Compositions described herein can also include a selenium source. Selenium is one of numerous trace metals found in many foods. In the compositions and method of the present disclosure, selenium may be employed as one of several non-toxic, water soluble organic or inorganic selenium sources in an assimilable form capable of being absorbed through the mucosal membrane. In other words, a selenium source for use in compositions and methods described herein shall include any compound or particle that, when administeredPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 to a mammalian subject, provides bioavailable selenium to the subject. Bioavailable elemental selenium refers to the fraction of elemental selenium (SeO) in a substance, such as selenomethionine, that can be absorbed and utilized by the body.

[0067] A selenium source for use in compositions and methods described herein can include inorganic or organic selenium compounds. Different chemical forms of selenium, including inorganic and organic forms have varying degrees of bioavailability. Exemplary inorganic selenium compounds are aliphatic selenium metal salts containing selenium in the form of selenite or selenate anions (e.g., sodium selenite and sodium selenate). However, organic selenium compounds are also usefully employable because they are normally less toxic than their inorganic counterparts. Other selenium compounds which may be mentioned by way of example include selenocystine, selenocysteine (SeCys), selenomethionine (SeMet), selenium-methylselenocysteine (MeSeCys), selenium glycinate, mono- and di-seleno carboxylic acids with about seven to eleven carbon atoms in the chain. Additional selenium sources can include selenium nanoparticles (SeNPs). For example, SeNPs have been produced using physical, biological, and chemical synthesis methods.

[0068] In certain embodiments, the selenium source can include, but is not limited to selenomethionine, selenocystine, sodium selenite, sodium selenate, methylselenocysteine, selenium glycinate, or a selenium nanoparticle., including salts, esters, anhydrides, tautomers, enantiomers, analogs, etc. of the individual selenium sources and combinations thereof. In certain embodiments, the selenium source is L-selenomethionine which is an enantiomer compound.

[0069] In and for all embodiments of the present disclosure, it is anticipated that the L- selenomethionine may be substituted by another selenium source, such as, but not limited to, selenomethionine and / or by a combination of selenium sources, wherein the selenium source may for example be selenium, and / or where the selenium source may be a compound or particle including a biologically assimilable form of selenium and / or a form of selenium that is bioavailable to the human body. Thus far, we have demonstrated that L-selenomethionine is highly useful for purposes of the present disclosure but anticipate it possible that other selenium compounds may be useful, such as selenium glycinate and / or sodium selenite and / or selenomethionine, or other.

[0070] It will be understood, however, that the particular forms of selenium sources set forth herein are not to be considered limitative. Other selenium sources, which exhibit the desired therapeutic activity and are compatible with the other components in a composition described herein, can be used in the practice of the invention.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3Subjects to be treated

[0071] Additional embodiments are provided that relate to the use of the therapeutic agents and pharmaceutical compositions thereof described herein to treat, prevent, or reduce the symptoms or severity of Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, cognitive decline, dementia, as well as any neural injury, neurodegeneration, neurodegenerative and / or neuropsychiatric condition, neurodegenerative and / or neuropsychiatric disease, and / or neurodegenerative and / or neuropsychiatric disorder in any subject in need thereof.

[0072] In some embodiments, a subject having the neural injury, neurodegeneration, neurodegenerative and / or neuropsychiatric condition, neurodegenerative and / or neuropsychiatric disease, and / or neurodegenerative and / or neuropsychiatric disorder can have or be at risk of memory loss, cognitive decline, axonal degeneration, neuronal cell death, glia cell damage, and / or blood brain barrier permeability, and a pharmaceutical composition described herein can be administered to the subject at an amount effective to inhibit a neural injury, neurodegeneration, neurodegenerative and / or neuropsychiatric condition, neurodegenerative and / or neuropsychiatric disease, and / or neurodegenerative and / or neuropsychiatric disorder in a subject, e.g., impeding its progress; and relieving the neural injury, neurodegeneration, neurodegenerative and / or neuropsychiatric condition, neurodegenerative and / or neuropsychiatric disease, and / or neurodegenerative and / or neuropsychiatric disorder, e.g., causing regression of the neural injury, neurodegeneration, neurodegenerative and / or neuropsychiatric condition, disease, and / or disorder. In some embodiments, treating the neural injury, neurodegenerative and / or neuropsychiatric condition, neurodegenerative and / or neuropsychiatric disease, and / or neurodegenerative and / or neuropsychiatric disorder can include ameliorating at least one symptom of the particular neural injury, neurodegeneration, in a subject in need thereof.

[0073] In some embodiments, subjects amenable to treatment by therapeutic agents and compositions thereof disclosed herein include subjects at risk of cognitive decline, Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, dementia, as well as any neural injury, neurodegeneration, neurodegenerative and / or neuropsychiatric condition, neurodegenerative and / or neuropsychiatric disease, and / or neurodegenerative and / or neuropsychiatric disorder, but not showing symptoms (for example asymptomatic subjects),PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 as well as subjects presently showing one or more symptoms. In the case of dementia related diseases, virtually anyone is at risk of suffering from dementia if he or she lives long enough. Therefore, the present methods can be administered prophylactically to the general population without any assessment of the risk of the subject patient.

[0074] In some embodiments, subjects can be screened for their likelihood of having or developing a cognitive decline, Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, dementia, as well as any neural injury, neurodegeneration, neurodegenerative and / or neuropsychiatric condition, neurodegenerative and / or neuropsychiatric disease, and / or neurodegenerative and / or neuropsychiatric disorder based on a number of biochemical and genetic markers. For example, subjects can be diagnosed with an increased risk of developing Alzheimer's Disease using genetic markers for Alzheimer's Disease.

[0075] Cognitive decline or indications, diseases, disorders, and / or conditions associated with cognitive decline or memory loss can be diagnosed using standard practice and the progression can be monitored over an extended period of time. One such method includes at least one of the following: (i) a memory assessment, (ii) an extensive neuropsychological exam, (iii) an examination by a geriatric neurologist and (iv) MRI imaging of the brain. Disease progression can be documented by changes in these parameters over time. In some embodiments, changes in the parameters of at least one of these assessments can be used to assess the efficacy of the pharmaceutical compositions and dosing regimens in the subject over time.

[0076] In some embodiments, the compositions and methods of the present disclosure are useful in treating or preventing cognitive decline, Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, dementia, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder.

[0077] In particular embodiments, the compositions and methods of the present disclosure are useful in treating or preventing cognitive decline, dementia, Parkinson’s disease or frontotemporal lobe dementia (FLD).

[0078] Parkinson’s disease treated in accordance with a method described herein can include any form of Parkinson’s disease(s) including, but not limited to, Idiopathic Parkinson’s, Early-Onset Parkinson’s, Familial Parkinson's, Secondary Parkinsonism, Drug- Induced Parkinsonism (DIP), Vascular Parkinsonism, Parkinson’s plus syndromes (alsoPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 known as Atypical Parkinsonism), Progressive Supranuclear Palsy, Dementia with Lewy bodies, Multiple System Atrophy (MSA), Corticobasal Syndrome, and any other forms of Parkinson’s disease.

[0079] In certain embodiments, the compositions and methods of the present disclosure are useful in treating or preventing Alzheimer’s disease and Alzheimer's disease related dementias in a subject in need thereof. Alzheimer's disease and related dementias (AD / ADRD) encompass a group of brain disorders that progressively impair memory, thinking, and social abilities, ultimately affecting a person's capacity to perform daily tasks. Alzheimer’s disease treated in accordance with a method described herein can include any known forms of Alzheimer’s disease such as by way of non-limiting example: early - stage Alzheimer’s, mid-stage Alzheimer’s, Type 1 Alzheimer’s, Type 2 Alzheimer’s , Type 1.5 Alzheimer’s, Type 3 Alzheimer’s, Type 4 Alzheimer’s, Type 5 Alzheimer’s, any other form of Alzheimer’s disease.

[0080] Dementias for which the therapeutic agents and compositions thereof are useful include any dementia related to and / or caused by Alzheimer's disease, vascular dementia from strokes, Lewy body dementia, and frontotemporal dementia, as well other mixed dementia, progressive supranuclear palsy (PSP), Parkinson's Disease with associated dementia, corticobasal degeneration, multiple system atrophy, HIV-induced dementia, white matter disease-associated dementias, mild cognitive impairment (MCI).

[0081] In some embodiments, the therapeutic agents and pharmaceutical compositions thereof described herein are useful in preventing and treating neurodegen erative conditions, diseases, or disorders including, but not limited to, subarachnoid hemorrhage, schizophrenia, depression, bipolar disorder, normal aging, epilepsy, traumatic brain injury and / or a visual symptom associated therewith, post-traumatic stress disorder, multiple system atrophy, corticobasal neurodegeneration, progressive supranuclear palsy, Alexander’s disease, Down syndrome, spinocerebellar ataxia, amyotrophic lateral sclerosis, Huntington’s disease, stroke, brain radiation therapy, chronic stress, abuse or cellular toxicity of a neuro-active drug, retinal degeneration, spinal cord injury, peripheral nerve injury, idiopathic peripheral neuropathy, cognitive decline and / or general frailty associated with normal aging and / or chemotherapy, chemotherapy induced neuropathy, concussive injury, peripheral nerve crush injury, peripheral neuropathy, diabetic neuropathy, post-traumatic headache, multiple sclerosis, retinal degeneration and dystrophy, Leber congenital amaurosis, retinitis pigmentosa, conerod dystrophy, microphthalmia, anophthalmia, myopia, and hyperopia, spinal cord injury, traumatic spinal cord injury, peripheral nerve injury, retinal neuronal death related diseases,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 retinal trauma, Autism, Stargardt disease, Kearns-Sayre syndrome, Pure neurosensory deafness, Hereditary hearing loss with retinal diseases, Hereditary hearing loss with system atrophies of the nervous system, Progressive spinal muscular atrophy, Progressive bulbar palsy, Primary lateral sclerosis, Hereditary forms of progressive muscular atrophy and spastic paraplegia, Frontotemporal dementia, Dementia with Lewy bodies, Corticobasal degeneration, Progressi ve supranuclear palsy, Prion disorders causing neurodegeneration, Multiple system atrophy. Hereditary spastic paraparesis, Friedreich ataxia, Non-Friedreich ataxia, Spinocerebellar atrophies, Amyloidoses, Metabolic-related neurodegenerative disorders, Toxin-related neurodegenerative disorders, Multiple sclerosis, Charcot Marie Tooth, Diabetic neuropathy, Metabolic neuropathies, Endocrine neuropathies, Creutzfeldt- Jacob Disease, Primary progressive aphasia, Frontotemporal Lobar Degeneration, Cortical blindness, Shy-Drager Syndrome, Diffuse cerebral cortical atrophy of non- Alzheimer type, Lewy-body dementia, Pick disease, Thalamic degeneration, Mesolimbocortical dementia of non-Alzheimer type, Nonhuntingtonian types of chorea and dementia, Cortical-striatal-spinal degeneration, Dementia-Parkinson-amyotrophic lateral sclerosis complex, Cerebrocerebellar degeneration, Cortico-basal ganglionic degeneration, Familial dementia with spastic paraparesis or myoclonus, Tourette syndrome, or viral infection.

[0082] Additional examples of neurodegenerative diseases or disorders for which the therapeutic agents and pharmaceutical compositions thereof described herein can be useful for can include, for example, polyglutamine repeat disorders such as Spinocerebellar ataxias (e.g., types 1, 2, 3, 6, 7 and 17), Machado-Joseph disease, Spinal and Bulbar muscular atrophy (SBMA or Kennedy's disease), Dentatorubral Pallidoluysian Atrophy (DRPLA) and other neurological conditions arising from polyglutamine expansions, or disease arising from non-coding DNA repeat expansions such as Fragile X syndrome, Fragile XE mental retardation, Friedreich ataxia, myotonic dystrophy, Spinocerebellar ataxias (types 8, 10 and 12) or other neurodegenerative diseases such as spinal muscular atrophy ( Werdnig-Hoffman disease, Kugelberg- Welander disease), and spongiform encephalopathies.

[0083] Additional neurodegenerative diseases for which therapeutic agents and compositions thereof described herein can be useful include, for example, age-related memory impairment, agyrophilic grain dementia, Parkinsonism-dementia complex of Guam, auto-immune conditions e.g., Guillain-Barre syndrome, Lupus), Biswanger's disease, brain and spinal tumors (including neurofibromatosis), cerebral amyloid angiopathies, cerebral palsy, chronic fatigue syndrome, corticobasal degeneration, conditions due to developmental dysfunction of the CNS parenchyma, conditions due to developmental dysfunction of thePCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 cerebrovasculature, dementia-multi infarct, dementia-subcortical, dementia with Lewy bodies, dementia of human immunodeficiency virus (HIV), dementia lacking distinct histology, Dementia Pugilistica, diffies neurofibrillary tangles with calcification, diseases of the eye, ear and vestibular systems involving neurodegeneration (including macular degeneration and glaucoma), dyskinesias (Paroxysmal), dystonias, essential tremor, Fahr's syndrome, fronto-temporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17), frontotemporal lobar degeneration, frontal lobe dementia, hepatic encephalopathy, hereditary spastic paraplegia, hydrocephalus, pseudotumor cerebri and other conditions involving CSF dysffunction, Gaucher's disease, Hallervorden-Spatz disease, Korsakoff s syndrome, mild cognitive impairment, monomeric amyotrophy, motor neuron diseases, multiple system atrophy, multiple sclerosis and other demyelinating conditions (e.g., leukodystrophies), myalgic encephalomyelitis, myoclonus, neurodegeneration induced by chemicals, drugs and toxins, neurological manifestations of AIDS including AIDS dementia, neurological / cognitive manifestations and consequences of bacterial and / or virus infections, including but not restricted to enteroviruses, Niemann-Pick disease, non-Guamanian motor neuron disease with neurofibrillary tangles, non-ketotic hyperglycinemia, olivo-ponto cerebellar atrophy, oculopharyngeal muscular dystrophy, neurological manifestations of Polio myelitis including non-paralytic polio and post-polio-syndrome, primary lateral sclerosis, prion diseases including Creutzfeldt-Jakob disease (including variant form), kuru, fatal familial insomnia, Gerstmann-Straussler-Scheinker disease and other transmissible spongiform encephalopathies, prion protein cerebral amyloid angiopathy, postencephalitic Parkinsonism, progressive muscular atrophy, progressive bulbar palsy, progressive subcortical gliosis, progressive supranuclear palsy, restless leg syndrome, Rett syndrome, Sandhoff disease, spasticity, sporadic fronto-temporal dementias, striatonigral degeneration, subacute sclerosing panencephalitis, sulphite oxidase deficiency, Sydenham's chorea, tangle only dementia, Tay- Sach's disease, Tourette’s syndrome, vascular dementia, and Wilson disease.

[0084] In some embodiments, the compositions and methods of the present disclosure are useful in treating or preventing a neuropsychiatric disease. A neuropsychiatric disease treated or prevented in accordance with a composition or method described herein can include any disorder where brain damage from an injury or illness causes behavioral, emotional, and cognitive changes that may often be mistaken for psychological problems.

[0085] In further embodiments, the compositions and methods of the present disclosure are useful in treating or preventing additional indications, diseases, disorders, and / or conditions, including but not limited to, CNS disorders, such as ADD, ADHD, BiPolarPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3Disorder, Major Depressive Disorder, Depression, Anxiety, Anger, Uncontrolled Anger, Rage disorders, Schizophrenia, Mania, Manic Depression, Psychosis, ALS; Parkinson-like syndromes, diseases of the Liver including but not limited to Metabolic dysfunction- associated steatohepatitis (MASH) (noting that liver values were excellent for our safety trial patient), diseases of the Eye especially age related diseases of the eye; and Erectile Dysfunction (ED) especially age related ED, where the compositions and / or methods of the present disclosure may be administered alone or in combination with other medications for these other indications, diseases, disorders, and / or conditions.Pharmaceutical Compositions, Doses and Dosage Regimens

[0086] Usefully, the compositions described herein are pharmaceutical compositions in which the individual therapeutic agent components, c.g., one or more of the benzimidazole, benzimidazole derivative or metabolites thereof and / or the selenium source and / or praziquantel constituents are combined with a pharmaceutically acceptable carrier.

[0087] A pharmaceutical composition containing one or more of the therapeutic agents described herein as an active ingredient may be manufactured by mixing the agent(s) with a pharmaceutically acceptable carrier(s) or an excipient(s) or diluting the agent(s) with a diluent in accordance with conventional methods. The pharmaceutical composition may further contain fillers, anti-cohesives, lubricants, wetting agents, flavoring agents, emulsifying agents, preservatives and the like. The pharmaceutical composition may be formulated into a suitable formulation in accordance with the methods known to those skilled in the art so that it can provide an immediate, controlled or sustained release of the therapeutic agent(s) after being administered into a subject in need thereof.

[0088] In particular embodiments, the pharmaceutical composition may be formulated into a parenteral or enteral (e.g., oral) dosage form. The solid dosage form for oral administration may be manufactured by adding excipient, if necessary, together with binder, disintegrants, lubricants, coloring agents, and / or flavoring agents, to the therapeutic agent(s) and shaping the resulting mixture into the form of tablets, sugar-coated pills, granules, powder or capsules. The additives that can be added in the composition may be ordinary ones in the art. For example, examples of the excipient include lactose, sucrose, sodium chloride, glucose, starch, calcium carbonate, kaolin, microcrystalline cellulose, silicate and the like. Exemplary binders include water, ethanol, propanol, sweet syrup, sucrose solution, starch solution, gelatin solution, carboxymethylcellulose, hydroxypropyl cellulose, hydroxypropyl starch, methylcellulose, ethylcellulose, shellac, calcium phosphonate andPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 polypyrrolidone. Examples of the disintegrant include dry starch, sodium arginate, agar powder, sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearic monoglyceride and lactose. Further, purified talc, stearates, sodium borate, and polyethylene glycol may be used as a lubricant; and sucrose, bitter orange peel, citric acid, tartanc acid, may be used as a flavoring agent. In some embodiments, the pharmaceutical composition can be made into aerosol formulations (e.g., they can be nebulized) to be administered via inhalation.

[0089] The one or more therapeutic agents described herein may be combined with flavoring agents, buffers, stabilizing agents, and the like and incorporated into oral liquid dosage forms such as solutions, syrups or elixirs in accordance with conventional methods. One example of the buffers may be sodium citrate. Examples of the stabilizing agents include tragacanth, acacia and gelatin.

[0090] In particular embodiments, one or more therapeutic agents can be formulated as an oral suspension. A pharmaceutically acceptable carrier in a suspension can include a liquid or semi-solid medium in which insoluble solid drug particles are dispersed, allowing for the stable and effective delivery of the medication. Suspensions typically include one or more therapeutic agents (e.g. fenbendazole, L-selenium, and / or praziquantel), a liquid vehicle (often water), a suspending agent (e.g. methylcellulose or xanthan gum), and other excipients such as thickening agents, preservatives, flavoring agents, and sweeteners.

[0091] In certain embodiments of the present disclosure, a benzimidazole , benzimidazole derivative or metabolite thereof administration of the present disclosure and / or the administration of compositions of the present disclosure that include the benzimidazole , benzimidazole derivative or metabolite thereof may be formulated to be included within a capsule, such as a softgel capsule (or gel cap), so as to include the largest possible dose capable of being easily swallowed by a subject. The softgel capsule can be comprised of a high quality fat, such as a high quality animal fat and / or cold pressed unrefined / unheated coconut oil, or such as may be a high quality chelated fish oil free of toxic substances, or such as may be included with a large dose of animal fat and / or cold pressed unrefined / unheated coconut oil such as may be about a fifty to one hundred gram mass of animal fat and / or cold pressed unrefined coconut oil. For example, any dosage of a benzimidazole, such as fenbendazole, according to the present disclosure and / or of any compositions of matter and / or substances of the present disclosure including benzimidazole may be mixed up and / or included into a fatty ice cream, or a fatty cheese spread, or a fatty desert, or a fatty pate, or a fatty snack bar, where an example of a useful fat is a healthy animal fat such as a fat of grass fed beef, goat, sheep, or is healthy animal milk fat such as used in forming an ice-cream ofPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 the present disclosure, or may be a healthy plant fat such as cold pressed unrefined coconut oil, and the dosing may be made by administering the food item including the healthy fat combined with the dosage of fenbendazole and / or any composition according to the present disclosure. In certain instances it may be desired that doses of compositions of the present disclosure and / or doses containing a benzimidazole of the present disclosure are administered multiple times daily so as to maximize the amount of healthy fat that is administered with each dose, for example, softgel capsules containing the doses of compositions of the present disclosure may be administered three to six times between morning and evening so as to maximize the potential for the compositions of matter and / or benzimidazole dose of the present disclosure to be present in the GI tract simultaneously with healthy fat from a healthy meal and / or from the dosing vector, that may be a softgel capsule, or dessert, or snack bar, or ice cream as described supra, and the needed daily maximal safe and effective doses thus divided between the individual doses so that taking all the individual doses results in taking the daily dose. However, in other embodiments, it is desirable that the entire daily dose be administered in a single dose event daily when the dose is administered (the term “daily” herein with respect to administration of a dose and / or with respect to dosages is understood as including to mean “during a 24 hour period”).

[0092] In some embodiments, the one or more therapeutic agent(s) described herein may be incorporated into an injection dosage form, for example, for a subcutaneous, intramuscular or intravenous route by adding thereto pH adjusters, buffers, stabilizing agents, relaxants, topical anesthetics. Examples of the pH adjusters and the buffers include sodium citrate, sodium acetate and sodium phosphate. Examples of the stabilizing agents include sodium pyrosulfite, EDTA, thioglycolic acid and thiolactic acid. The topical anesthetics may be procaine HC1, lidocaine HC1 and the like. The relaxants may be sodium chloride, glucose and the like.

[0093] In other embodiments, the one or more therapeutic agent(s) described herein may be incorporated into suppository dosage forms in accordance with conventional methods by adding thereto pharmaceutically acceptable carriers that are known in the art, for example, polyethylene glycol, lanolin, cacao butter or fatty acid triglycerides, if necessary, together with surfactants such as Tween.

[0094] The pharmaceutical composition may be formulated into various dosage forms as discussed above and then administered through various routes including an oral, inhalational, transdermal, subcutaneous, intravenous or intramuscular route.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3

[0095] As our experiments have further demonstrated, and as we now disclose herein, the benzimidazole and the selenium source (e.g., fenbendazole and L- selenomethionine) and the praziquantel may each be administered separately during the same treatment period and / or dosing event, or they may all be included in a pharmaceutical composition comprising the benzimidazole and the selenium source, and the praziquantel in one composition, that may be an oral suspension. In an exemplary embodiment, an oral suspension formulation for use in methods described herein may comprise, in addition to a benzimidazole and / or a selenium source and / or praziquantel, any or all of the following: methylparaben (UNII: A2I8C7HI9T) ; propylparaben (UNII: Z8IX2SC1OH); silicon dioxide (UNII: ETJ7Z6XBU4);CARBOXYMETHYLCELLULOSE SODIUM, UNSPECIFIED (UNII: K679OBS311);POVIDONE, UNSPECIFIED (UNII: FZ989GH94E); trisodium citrate dihydrate (UNII: B22547B95K); citric acid monohydrate (UNII: 2968PHW8QP);and / or purified water (UNII: 059QF0KO0R).

[0096] In particular embodiments, an oral suspension of a benzimidazole described herein and in the dosages described herein, may contain any or all of the following, and where the benzimidazole may comprise ten percent or about ten percent by weight of the suspension, presently is disclosed: methylparaben (UNII: A2I8C7HI9T) ; propylparaben (UNII: Z8IX2SC1OH); silicon dioxide (UNII: ETJ7Z6XBU4);CARBOXYMETHYLCELLULOSE SODIUM, UNSPECIFIED (UNII: K679OBS311);POVIDONE, UNSPECIFIED (UNII: FZ989GH94E); trisodium citrate dihydrate (UNII: B22547B95K); citric acid monohydrate (UNII: 2968PHW8QP);and / or purified water (UNII: 059QF0KO0R).

[0097] In an exemplary embodiment, a presently disclosed oral suspension can be obtained by starting with a product known by the brand name Panacur® 10%, (that may be sold and / or produced and / or offered and / or owned by MSD Animal Health), having as it’sPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 active ingredient fenbendazole and / or fenbendazole (UNII: 621BVT9M36) (fenbendazole - UNII:621BVT9M36), and adding to it the L-selenomethionine and / or the praziquantel, in the above described dosages, while (optionally) ensuring that the level of the fenbendazole remains at ten percent or about ten percent, or in a range of about five percent to about 25 percent of the suspension by weight, and, optionally, by also ensuring that the proper and desired levels and / or quantities and / or dosages of the L-selenomethionine and / or the praziquantel are present in the suspension. The resulting suspension or any suspension comprising the active ingredients of the present disclosure may also be blended with a food substance such as a yogurt, pudding, ice cream, or the like and preserved in individual singleuse and / or one-time-use containers, configured for easy consumption of the contents. Usefully, at least 50 ml or 50 grams of a high-quality animal fat are included in the food substance. A suitable animal fat may be grass fed butter from goat, sheep or cow milk.

[0098] Significant challenges in using certain benzimidazoles, such as fenbendazole, for systemic therapies, include low water solubility and bioavailability. Therefore, in some embodiments, compositions including a benzimidazole, such as fenbendazole, can include a vehicle to improve the solubility of the benzimidazole administered to a subject. Exemplary vehicles to improve the solubility of a benzimidazole or composition thereof when administered to a subject can include (D,L-lactide-co-glycolide) acid (PLGA) nanoparticles or a triblock copolymer (e.g., PVC, PVA and PEG copolymer) micelles to encapsulate the benzimidazole, DMSO, DNTC (z.e., DMSO, NMP, Tween-80 and Cremophor mix in 1 :3:2:2 ratio), methyl-P-cyclodextrin complexed to a benzimidazole (where for example the fenbendazole or other benzimidazole may be formed in a complex with methyl-P- cyclodextrin at a 1 : 1 ratio, and then additionally combined and / or administered with the bioavailable selenium as disclosed herein, that may be L-selenomethionine), as well as one or more supplementary vitamins (e.g., A / retinol, D3 / Cholecalciferol, E K3, Bl, B2, B6, B12, folate, niacin, pantothenic acid, and biotin) and / or cocrystals (e.g., cinnamic, benzoic and salicylic acids).

[0099] The dose and / or dosages can be a pharmaceutically or therapeutically effective amount. Therapeutically effective dosages of one or more therapeutic agents or a pharmaceutical composition thereof described herein can include the dosage that generates the maximum therapeutic effect at treating, or that generates the maximum protective effect in preventing any or all of the indications including Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, dementia, cognitive decline, neural injury, neurodegeneration,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or a neuropsychiatric disorder or reduces at least one symptom of Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, dementia, cognitive decline, a neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or a neuropsychiatric disorder in the subject.

[0100] In some embodiments, an effective dosage causes at least a statistically or clinically significant attenuation of at least one marker, symptom, or histological evidence characteristic of Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or a neuropsychiatric disorder. In exemplary embodiments, the subject has memory loss and / or cognitive decline, and the pharmaceutical composition is administered at an amount effective to ameliorate memory loss and / or cognitive decline and / or improve memory and / or cognition.

[0101] Markers, symptoms and histological evidence characteristic of Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease, frontotemporal lobe dementia, dementia, cognitive decline, neural injury, neurodegeneration and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or a neuropsychiatric disorder described above can without limitation include memory loss, confusion, depression, anxiety, anger, uncontrolled anger or rage, mania, psychosis, disturbances in axonal transport, demyelination, induction of metalloproteinases (MMPs), activation of glial cells, infiltration of lymphocytes, edema and immunological reactions that lead to CNS tissue damage and further vascular injury. Cessation, resolution, stabilization, amelioration, inhibition or a reduction of one or more symptoms and / or a diminution of tissue damage, under conditions wherein control patients or animals experience a worsening of symptoms or tissue damage, is one indicator of efficacy of a suppressive treatment.

[0102] Additional embodiments relate to the use of the therapeutic agents and / or compositions thereof for the treatment of cancer. A composition described herein and / or methods as described herein and / or methods of administration of agents and / or one or morePCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 therapeutic agents as described herein can be used as the sole method of treatment, or it can be combined with other methods and / or therapeutics for treating the cancer.

[0103] “Cancer" or "malignancy" are used as synonymous terms and refer to any of a number of diseases that are characterized by uncontrolled, abnormal proliferation of cells, the ability of affected cells to spread locally or through the bloodstream and lymphatic system to other parts of the body (i.e. , metastasize) as well as any of a number of characteristic structural and / or molecular features. A "cancer cell" refers to a cell undergoing early, intermediate or advanced stages of multi-step neoplastic progression. The features of early, intermediate and advanced stages of neoplastic progression have been described using microscopy. Cancer cells at each of the three stages of neoplastic progression generally have abnormal karyotypes, including translocations, inversion, deletions, isochromosomes, monosomies, and extra chromosomes. Cancer cells include "hyperplastic cells," that is, cells in the early stages of malignant progression, "dysplastic cells," that is, cells in the intermediate B stages of neoplastic progression, and "neoplastic cells," that is, cells in the advanced stages of neoplastic progression.

[0104] The cancers treated using compositions of the present disclosure can include any neoplastic growth in a subject, including an initial tumor and any metastases. The cancer can be of the liquid or solid tumor type. Liquid tumors include tumors of hematological origin, including but not limited to, e.g., myelomas (e.g., multiple myeloma), leukemias (e.g., Waldenstrom's syndrome, chronic lymphocytic leukemia, other leukemias), and lymphomas (e.g., B-cell lymphomas, non-Hodgkin’s lymphoma). In certain embodiments the cancer treated is a solid tumor. Solid tumors can originate in organs and can include, but are not limited to, cancers of the lungs, brain, breasts, prostate, ovaries, colon, kidneys and liver.

[0105] In some embodiments, cancers treated in accordance with methods described herein include breast cancer, lung cancer, prostate cancer, pancreatic cancer, cancers of the brain, brain tumors, brain cancer and other nervous system cancer, esophageal cancer, liver cancer and / or intrahepatic bile duct cancer, acute myeloid leukemia, stomach cancer, myeloma, laryngeal cancer, anaplastic thyroid cancer, colorectal cancer, Non-Hodgkin Lymphoma, or ovarian cancer.

[0106] The benzimidazole agent, fenbendazole, has been shown to demonstrate antitumor effects against multiple cancer types, including but not limited to, non-small cell lung cancer (NSCLC), skin cancer {e.g, melanoma), cervical cancer, colorectal cancer, leukemia, hepatocellular carcinoma, breast cancer (e.g., estrogen receptor positive (ER+) breast cancer and triple negative breast cancer (TNBC)). Therefore, in some embodiments, cancers treatedPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 in accordance with methods described herein include non-small cell lung cancer (NSCLC), skin cancer (e.g, melanoma), cervical cancer, colorectal cancer, leukemia, hepatocellular carcinoma, breast cancer e.g., estrogen receptor positive (ER+) breast cancer and triple negative breast cancer (TNBC).

[0107] Additional cancers treated using compositions and methods described herein can include the following: leukemias, such as but not limited to, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemias, such as, myeloblastic, promyelocytic, myelomonocytic, monocytic, and erythroleukemia leukemias and myelodysplastic syndrome; chronic leukemias, such as but not limited to, chronic myelocytic (granulocytic) leukemia, chronic lymphocytic leukemia, hairy cell leukemia; polycythemia vera; lymphomas such as but not limited to Hodgkin's disease, non-Hodgkin's disease; multiple myelomas such as but not limited to smoldering multiple myeloma, nonsecretory myeloma, osteosclerotic myeloma, plasma cell leukemia, solitary plasmacytoma and extramedullary plasmacytoma;Waldenstrom's macroglobulinemia; monoclonal gammopathy of undetermined significance; benign monoclonal gammopathy; heavy chain disease; bone and connective tissue sarcomas such as but not limited to bone sarcoma, osteosarcoma, chondrosarcoma, Ewing's sarcoma, malignant giant cell tumor, fibrosarcoma of bone, chordoma, periosteal sarcoma, soft-tissue sarcomas, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi's sarcoma, leiomyosarcoma, liposarcoma, lymphangiosarcoma, neurilemmoma, rhabdomyosarcoma, synovial sarcoma; brain tumors such as but not limited to, glioma, astrocytoma, glioblastoma, brain stem glioma, ependymoma, oligodendroglioma, nonglial tumor, acoustic neurinoma, craniopharyngioma, medulloblastoma, meningioma, pineocytoma, pineoblastoma, primary brain lymphoma; breast cancer including but not limited to ductal carcinoma, adenocarcinoma, lobular (small cell) carcinoma, intraductal carcinoma, medullary breast cancer, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget's disease, and inflammatory breast cancer; adrenal cancer such as but not limited to pheochromocytoma and adrenocortical carcinoma; thyroid cancer such as but not limited to papillary or follicular thyroid cancer, medullary thyroid cancer and anaplastic thyroid cancer; pancreatic cancer such as but not limited to, insulinoma, gastrinoma, glucagonoma, vipoma, somatostatinsecreting tumor, and carcinoid or islet cell tumor; pituitary cancers such as but limited to Cushing's disease, prolactin-secreting tumor, acromegaly, and diabetes insipius; eye cancers such as but not limited to ocular melanoma such as iris melanoma, choroidal melanoma, and cilliary body melanoma, and retinoblastoma; vaginal cancers such as squamous cell carcinoma, adenocarcinoma, and melanoma; vulvar cancer such as squamous cell carcinoma,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, and Paget's disease; cervical cancers such as but not limited to, squamous cell carcinoma, and adenocarcinoma; uterine cancers such as but not limited to endometrial carcinoma and uterine sarcoma; ovarian cancers such as but not limited to, ovarian epithelial carcinoma, borderline tumor, germ cell tumor, fallopian tube cancer, and stromal tumor; esophageal cancers such as but not limited to, squamous cancer, adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, sarcoma, melanoma, plasmacytoma, verrucous carcinoma, and oat cell (small cell) carcinoma; stomach cancers such as but not limited to, adenocarcinoma, fungating (polypoid), ulcerating, superficial spreading, diffusely spreading, malignant lymphoma, liposarcoma, fibrosarcoma, and carcinosarcoma; colon cancers; rectal cancers; liver cancers such as but not limited to hepatocellular carcinoma and hepatoblastoma; gallbladder cancers such as adenocarcinoma; cholangiocarcinomas such as but not limited to papillary, nodular, and diffuse; lung cancers such as non-small cell lung cancer, squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large-cell carcinoma and small-cell lung cancer; testicular cancers such as but not limited to germinal tumor, seminoma, anaplastic, classic (typical), spermatocytic, nonseminoma, embryonal carcinoma, teratoma carcinoma, choriocarcinoma (yolk-sac tumor), prostate cancers such as but not limited to, prostatic intraepithelial neoplasia, adenocarcinoma, leiomyosarcoma, and rhabdomyosarcoma; penal cancers; oral cancers such as but not limited to squamous cell carcinoma; basal cancers; salivary gland cancers such as but not limited to adenocarcinoma, mucoepidermoid carcinoma, and adenoidcystic carcinoma; pharynx cancers such as but not limited to squamous cell cancer, and verrucous; skin cancers such as but not limited to, basal cell carcinoma, squamous cell carcinoma and melanoma, superficial spreading melanoma, nodular melanoma, lentigo malignant melanoma, acral lentiginous melanoma; kidney cancers such as but not limited to renal cell carcinoma, adenocarcinoma, hypernephroma, fibrosarcoma, transitional cell cancer (renal pelvis and / or uterer); Wilms' tumor; bladder cancers such as but not limited to transitional cell carcinoma, squamous cell cancer, adenocarcinoma, carcinosarcoma. In addition, cancers include myxosarcoma, osteogenic sarcoma, endotheliosarcoma, lymphangioendotheliosarcoma, mesothelioma, synovioma, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma and papillary adenocarcinomas (for a review of such disorders, see Fishman et al., 1985, Medicine, 2d Ed., J. B. Lippincott Co., Philadelphia and Murphy et al., 1997, Informed Decisions: ThePCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3Complete Book of Cancer Diagnosis, Treatment, and Recovery, Viking Penguin, Penguin Books U.S.A., Inc., United States of America).

[0108] In some embodiments, the subject being administered a therapeutically effective amount of a composition described herein is a subject who has been identified as having cancer. As is known to those skilled in the art, there are a variety of methods of identifying (z.e., diagnosing) a subject who has cancer. For example, diagnosis of cancer can include one or more of a physical exam, laboratory tests, imaging analysis, and biopsy. After cancer is diagnosed, a variety of tests may be carried out to look for specific features characteristic of different types and or the extent of cancer in the subject. These tests include, but are not limited to, bone scans, X-rays, immunopheno typing, flow cytometry, and fluorescence in situ hybridization testing. For example, typical methods of diagnosing triple-negative breast cancer can include, but are not limited to, a physical exam, digital mammogram, breast MRI, breast ultrasound, stereotactic core and / or open tumor biopsy, as well as lab tests to determine if the tumor tissue expresses estrogen, progesterone, and HER-2 / neu or not.

[0109] Alternately, the composition can be administered to a subject who has not been diagnosed with cancer as a means of preventing or decreasing the risk or likelihood of cancer development. In some embodiments, the subject being treated using compositions described herein has been characterized as being a subject having a high or increased risk of developing cancer. Subjects can be characterized as being at high or increased risk of developing cancer as a result of, for example, family history, genetic testing, or high exposure to cancer-causing environmental conditions. The benzimidazole, fenbendazole, has been shown to have antitumor effects against cancer cells that have become resistant to chemotherapeutic agents. Therefore, it is further contemplated that the cancer treated in accordance with the compositions and methods described herein can include a chemotherapeutic resistant cancer, such as but not limited to 5-FU (Fluorouracil), paxlitaxel and docetaxel resistant cancers. Beyond cancers, fenbendazole has been shown to inhibit the progression of lung fibrosis resulting from the chemotherapy drug bleomycin. Therefore, it is also contemplated that compositions and methods described herein can used to treat lung fibrosis in a subject, such as bleomycin-induced pulmonary fibrosis (BIPF)

[0110] Compositions described herein for the treatment of cancer may be administered alone or in conjunction with other cancer agents or antineoplastic agents or other growth inhibiting agents or other drugs, agents, or nutrients, as in an adjunct therapy. The phrase "adjunct therapy" or "combination therapy" in defining use of a composition described supra (e.g., a composition that includes a benzimidazole, a selenium source and optionallyPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 praziquantel) and one or more other pharmaceutical agents or therapies, is intended to embrace administration of each agent and / or cancer therapy in a sequential manner in a regimen that will provide beneficial effects of the drug combination, and is intended as well to embrace co-administration of these agents and / or cancer therapies in a substantially simultaneous manner, such as in a single formulation of therapeutic agents having a fixed ratio of these active agents, or in multiple, separate formulations for each agent.

[0111] In some embodiments, a method of treating cancer described herein can include administering an additional therapeutic or cancer therapy to the subject. A "cancer therapeutic” or “cancer therapy”, as used herein, can include any agent or treatment regimen that is capable of negatively affecting cancer in an animal, for example, by killing cancer cells, inducing apoptosis in cancer cells, reducing the growth rate of cancer cells, reducing the incidence or number of metastases, reducing tumor size, inhibiting tumor growth, reducing the blood supply to a tumor or cancer cells, promoting an immune response against cancer cells or a tumor, preventing or inhibiting the progression of cancer, or increasing the lifespan of an animal with cancer. Cancer therapeutics can include one or more therapies such as, but not limited to, chemotherapies, radiation therapies, hormonal therapies, and / or biological therapies / immuno therapies. A reduction, for example, in cancer, cancer cell, and / or tumor volume, growth, migration, and / or dispersal in a subject may be indicative of the efficacy of a given cancer therapy or combination of therapies described above.

[0112] In some embodiments, such as for the purposes of combination therapy, the method can include the step of administering a therapeutically effective amount of an additional anticancer therapeutic agent to the subject. Additional anticancer therapeutic agents can be in the form of biologically active ligands, small molecules, peptides, polypeptides, proteins, DNA fragments, DNA plasmids, interfering RNA molecules, such as siRNAs, oligonucleotides, and DNA encoding for shRNA. In some embodiments, cytotoxic compounds are included in an anticancer agent described herein. Cytotoxic compounds include small-molecule drugs such as doxorubicin, methotrexate, vincristine, and pyrimidine and purine analogs, referred to herein as antitumor agents. In particular embodiments, an additional anticancer therapeutic agent can include a corticosteroid such as but not limited to prednisone.

[0113] The additional anticancer therapeutic agent can include an anticancer or an antiproliferative agent that exerts an antineoplastic, chemotherapeutic, antiviral, antimitotic, antitumorgenic, and / or immunotherapeutic effects, e.g., prevent the development, maturation, or spread of neoplastic cells, directly on the tumor cell, e.g., by cytostatic or cytocidal effects,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 and not indirectly through mechanisms such as biological response modification. There are large numbers of anti-proliferative agents available in commercial use, in clinical evaluation and in pre-clinical development. For convenience of discussion, anti-proliferative agents are classified into the following classes, subtypes and species: ACE inhibitors, alkylating agents, angiogenesis inhibitors, angiostatin, anthracyclines / DNA intercalators, anti-cancer antibiotics or antibiotic-type agents, antimetabolites, antimetastatic compounds, asparaginases, bisphosphonates, cGMP phosphodiesterase inhibitors, calcium carbonate, cyclooxygenase-2 inhibitors, DHA derivatives, DNA topoisomerase, endostatin, epipodophylotoxins, genistein, hormonal anticancer agents, hydrophilic bile acids (URSO), immunomodulators or immunological agents, integrin antagonists, interferon antagonists or agents, MMP inhibitors, miscellaneous antineoplastic agents, monoclonal antibodies, nitrosoureas, NSAIDs, ornithine decarboxylase inhibitors, pBATTs, radio / chemo sensitizers / protectors, retinoids, selective inhibitors of proliferation and migration of endothelial cells, stromelysin inhibitors, taxanes, vaccines, and vinca alkaloids.

[0114] The major categories that some anti-proliferative agents fall into include antimetabolite agents, alkylating agents, antibiotic-type agents, hormonal anticancer agents, immunological agents, interferon-type agents, and a category of miscellaneous antineoplastic agents. Some anti-proliferative agents operate through multiple or unknown mechanisms and can thus be classified into more than one category.

[0115] Examples of anticancer therapeutic agents that can be administered in combination with an compositions described herein include Taxol, Adriamycin, dactinomycin, bleomycin, vinblastine, cisplatin, acivicin; aclarubicin; acodazole hydrochloride; acronine; adozelesin; aldesleukin; altretamine; ambomycin; ametantrone acetate; aminoglutethimide; amsacrine; anastrozole; anthramycin; asparaginase; asperlin; azacitidine; azetepa; azotomycin; batimastat; benzodepa; bicalutamide; bisantrene hydrochloride; bisnafide dimesylate; bizelesin; bleomycin sulfate; brequinar sodium; bropinmine; busulfan; cactinomycin; calusterone; caracemide; carbetimer; carboplatin; carmustine; carubicin hydrochloride; carzelesin; cedefingol; chlorambucil; cirolemycin; cladribine; crisnatol mesylate; cyclophosphamide; cytarabine; dacarbazine; daunorubicin hydrochloride; decitabine; dexormaplatin; dezaguanine; dezaguanine mesylate; diaziquone; doxorubicin; doxorubicin hydrochloride; droloxifene; droloxifene citrate; dromostanolone propionate; duazomycin; edatrexate; eflomithine hydrochloride; elsamitrucin; enloplatin; enpromate; epipropidine; epirubicin hydrochloride; erbulozole; esorubicin hydrochloride; estramustine; estramustine phosphate sodium; etanidazole; etoposide; etoposide phosphate;PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 etoprine; fadrozole hydrochloride; fazarabine; fenretimde; floxuridine; fludarabine phosphate; fluorouracil; fluorocitabine; fosquidone; fostriecin sodium; gemcitabine; gemcitabine hydrochloride; hydroxyurea; idarubicin hydrochloride; ifosfamide; ilmofosine; interleukin II (including recombinant interleukin II, or rIL2), interferon alfa-2a; interferon alfa-2b; interferon alfa-nl; interferon alfa-n3; interferon beta-I a; interferon gamma-I b; iproplatin; irinotecan hydrochloride; lanreotide acetate; letrozole; leuprolide acetate; liarozole hydrochloride; lometrexol sodium; lomustine; losoxantrone hydrochloride; masoprocol; maytansine; mechlorethamine hydrochloride; megestrol acetate; melengestrol acetate; melphalan; menogaril; mercaptopurine; methotrexate; methotrexate sodium; metoprine; meturedepa; mitindomide; mitocarcin; mitocromin; mitogillin; mitomalcin; mitomycin; mitosper; mitotane; mitoxantrone hydrochloride; mycophenolic acid; nocodazole; nogalamycin; ormaplatin; oxisuran; pegaspargase; peliomycin; pentamustine; peplomycin sulfate; perfosfamide; pipobroman; piposulfan; piroxantrone hydrochloride; plicamycin; plomestane; porfimer sodium; porfiromycin; prednimustine; procarbazine hydrochloride; puromycin; puromycin hydrochloride; pyrazofurin; riboprine; rogletimide; safingol; safmgol hydrochloride; semustine; simtrazene; sparfosate sodium; sparsomycin; spirogermanium hydrochloride; spiromustine; spiroplatin; streptonigrin; streptozocin; sulofenur; talisomycin; tecogalan sodium; tegafur; temozolomide, teloxantrone hydrochloride; temoporfin; teniposide; teroxirone; testolactone; thiamiprine; thioguanine; thiotepa; tiazofurin; tirapazamine; toremifene citrate; trestolone acetate; triciribine phosphate; trimetrexate; trimetrexate glucuronate; tnptorelin; tubulozole hydrochloride; uracil mustard; uredepa; vapreotide; verteporfm; vinblastine sulfate; vincristine sulfate; vindesine; vindesine sulfate; vinepidine sulfate; vinglycinate sulfate; vinleurosine sulfate; vinorelbine tartrate; vinrosidine sulfate; vinzolidine sulfate; vorozole; zeniplatin; zinostatin; zorubicin hydrochloride.

[0116] In certain embodiments, additional anticancer therapeutic agents administered to a subject for the treatment of a cancer, such as triple negative breast cancer, as described herein can include one or more of an anthracycline, such as adriamycin, an alkylating agent such as Cytoxan (cyclophosphamide), an antimetabolite such as Fluorouracil (5FU), and a taxane, such as Taxol or Taxotere. In other embodiments, additional anticancer therapeutic agents administered to a subject for the treatment of cancer, such as melanoma, as described herein can include one or more of Aldesleukin, Binimetinib, Braftovi (Encorafenib), Cobimetinib, Cotellic (Cobimetinib), Dabrafenib Mesylate, Dacarbazine, Encorafenib, Imlygic (Talimogene Laherparepvec), Intron A (Recombinant Interferon Alfa-2b), Keytruda (Pembrolizumab), Mekinist (Trametinib), Mektovi (Binimetinib), Nivolumab, OpdivoPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3(Nivolumab), Peginterferon Alfa-2b, PEG-Intron (Peginterferon Alfa-2b), Recombinant Interferon Alfa-2b, Sylatron (Peginterferon Alfa- 2b), Tafinlar (Dabrafenib Mesylate), Talimogene Laherparepvec, Trametinib, Vemurafenib, Yervoy (Ipilimumab), and Zelboraf (Vemurafenib).

[0117] In some embodiments, the anti-cancer therapy administered to the subject in addition to the compositions and methods described herein can include the cancer ablation therapy. Ablating the cancer can be accomplished using a method selected from the group consisting of cryoablation, thermal ablation, radiotherapy, chemotherapy, radiofrequency ablation, electroporation, alcohol ablation, high intensity focused ultrasound, photodynamic therapy, administration of monoclonal antibodies, immunotherapy, and administration of immunotoxins. Another method of ablating cancer, such as breast cancer, that has been treated with an anti-cancer particle composition of the present invention is to conduct surgery to remove the cancer tissue (e.g., breast cancer tissue) from the subject. Types of surgery for breast cancer vary depending on the nature of the breast cancer, and include lumpectomy, partial or segmental mastectomy or quadrantectomy, simple or total mastectomy, radical mastectomy, and modified radical mastectomy. Appropriate surgeries for treating other types of cancer are known to those skilled in the art.

[0118] In some embodiments, ablating the cancer includes immunotherapy of the cancer. Cancer immunotherapy is based on therapeutic interventions that aim to utilize the immune system to combat malignant diseases. It can be divided into unspecific approaches and specific approaches. Unspecific cancer immunotherapy aims at activating parts of the immune system generally, such as treatment with specific cytokines known to be effective in cancer immunotherapy e.g., IL-2, interferon's, cytokine inducers). In contrast, specific cancer immunotherapy is based on certain antigens that are preferentially or solely expressed on cancer cells or predominantly expressed by other cells in the context of malignant disease (usually in vicinity of the tumor site). Specific cancer immunotherapy can be grouped into passive and active approaches.

[0119] In passive specific cancer immunotherapy substances with specificity for certain structures related to cancer that are derived from components of the immune system are administered to the patient. The most prominent and successful approaches are treatments with humanized or mouse / human chimeric monoclonal antibodies against defined cancer associated structures (such as Trastuzumab, Rituximab, Cetuximab, Bevacizumab, Alemtuzumab). The pharmacologically active substance exerts is activity as long as aPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 sufficient concentration is present in the body of the patient, therefore administrations have to be repeated based on pharmacokinetic and pharmacodynamic considerations.

[0120] On the other hand, active specific cancer immunotherapy aims at antigenspecific stimulation of the patient's immune system to recognize and destroy cancer cells. Active specific cancer immunotherapy therefore, in general, is a therapeutic vaccination approach. There are many types of cancer vaccine approaches being pursued, such as vaccination with autologous or allogeneic whole tumor cells (in most cases genetically modified for better immune recognition), tumor cell lysates, whole tumor associated antigens (produced by means of genetic engineering or by chemical synthesis), peptides derived from protein antigens, DNA vaccines encoding for tumor associated antigens, surrogates of tumor antigens such as anti-idiotypic antibodies used as vaccine antigens, and the like. These manifold approaches are usually administered together with appropriate vaccine adjuvants and other immunomodulators in order to elicit a quantitatively and qualitatively sufficient immune response (many novel vaccine adjuvant approaches are being pursued in parallel with the development of cancer vaccines). Another set of cancer vaccine approaches relies on manipulating dendritic cells (DC) as the most important antigen presenting cell of the immune system. For example, loading with tumor antigens or tumor cell lysates, transfection with genes encoding for tumor antigens and in-vivo targeting are suitable immunotherapies that can be used together with the compositions and methods described herein of the invention for cancer treatment.

[0121] In some embodiments, ablating the cancer includes administering a therapeutically effective amount of radiotherapy (RT) to the subject. Radiotherapy uses high- energy rays to treat disease, usually x-rays and similar rays (such as electrons). Radiotherapy administered to a subject can include both external and internal. External radiotherapy (or external beam radiation) aims high-energy x-rays at the tumor site including in some cases the peri-tumor margin. External radiotherapy typically includes the use of a linear accelerator (e.g., a Varian 2100C linear accelerator). External radiation therapy can include three- dimensional conformal radiation therapy (3D-CRT), image guided radiation therapy (IGRT), intensity modulated radiation therapy (IMRT), helical-tomotherapy, photon beam radiation therapy, proton beam radiation therapy, stereotactic radiosurgery and / or sterotactic body radiation therapy (SBRT).

[0122] Internal radiotherapy (brachytherapy) involves having radioactive material placed inside the body and allows a higher dose of radiation in a smaller area than might be possible with external radiation treatment. It uses a radiation source that is usually sealed inPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 an implant. Exemplary implants include pellets, seeds, ribbons, wires, needles, capsules, balloons, or tubes. Implants are placed in the body, very close to or inside the tumor. Internal radiotherapy can include intracavitary or interstitial radiation. During intracavitary radiation, the radioactive source is placed in a body cavity (space), such as the uterus. With interstitial radiation, the implants are placed in or near the tumor, but not in a body cavity.In some embodiments, an immune checkpoint inhibitor can be further administered to eradicate suppressive regulatory T cells prior to RT. Exemplary checkpoint inhibitors can include CTLA4 and PD-l / PDL-1 inhibitors. The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1) immune checkpoints are negative regulators of T- cell immune function and inhibition of these targets, results in increased activation of the immune system. Therefore, in some embodiments, a checkpoint inhibitor administered to a subject can include a CTLA-4 and / or PD-1 inhibitor. For example, Ipilimumab, an inhibitor of CTLA-4, is approved for the treatment of advanced or unresectable melanoma.Nivolumab and pembrolizumab, both PD-1 inhibitors, are approved to treat patients with advanced or metastatic melanoma and patients with metastatic, refractory non-small cell lung cancer. In addition, the combination of ipilimumab and nivolumab has been approved in patients with BRAF WT metastatic or unresectable melanoma. In some embodiments, an immune checkpoint agonistic agent, such as an 0X40 agonistic agent, can be further administered to promote immune activation of cytotoxic T-cells.

[0123] The administration of benzimidazoles, such as fenbendazole, can be especially toxic, even at low doses, to subjects with compromised liver function, liver cirrhosis, and / or liver cancer. Therefore, although we have demonstrated in our human trials that our composition and methods that comprise administration of fenbendazole with a bioavailable selenium source, such as L-selenomethionine, appears to have the effect of rendering fenbendazole safe and in particular! non-hepatoxic in doses and dosages that are well in excess of one hundred percent and even in excess of four hundred percent the doses and dosages of fenbendazole that have been previously reported as having been used when fenbendazole is administered to human patients as an adjunct therapy or even as a monotherapy for cancer, it is theorized that, usefully, in additional embodiments, compositions and methods described herein can further include the use of a glycolysis inhibitor and / or hepatoprotective pharmaceutical or nutraceutical agents. For example, one or more glycolysis inhibitors, hepatoprotective pharmaceutical agents, and / or hepatoprotective nutraceutical agents can be included in a composition for the treatment of anPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 indication described herein and / or administered in conjunction with a composition in accordance with a method described herein.

[0124] In other embodiments, a pharmaceutical antiviral therapeutic agent or agents, alone or in combinations, such as may be acyclovir, valacyclovir, and famciclovir, may be included in the present disclosures compositions or may be used as agents in enacting the present disclosure’s methods, including in known doses and dosages established for antiviral agents.

[0125] Therapeutically effective dosage amounts of one or more therapeutic agents or a pharmaceutical composition thereof described herein may be present in varying amounts in various embodiments.

[0126] Particular doses or amounts to be administered in accordance with a method of the present disclosure may vary, for example, depending on the nature and / or extent of the desired outcome, on particulars of route and / or timing of administration, and / or on one or more characteristics (e.g., weight, age, personal history, genetic characteristic, lifestyle parameter, severity of cardiac defect and / or level of risk of cardiac defect, etc., or combinations thereof). Such doses or amounts can be determined by those of ordinary skill. In some embodiments, an appropriate dose or amount is determined in accordance with standard clinical techniques. For example, in some embodiments, an appropriate dose or amount is a dose or amount sufficient to reduce a disease severity index score by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100% or more. For example, in some embodiments, an appropriate dose or amount is a dose or amount sufficient to reduce a disease severity index score by 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100%. Alternatively, or additionally, in some embodiments, an appropriate dose or amount is determined through use of one or more in vitro or in vivo assays to help identify desirable or optimal dosage ranges or amounts to be administered.

[0127] Various embodiments may include differing dosing regimens. In some useful embodiments, the one or more therapeutic agents or a pharmaceutical composition thereof described herein can be administered orally by the subject. In other embodiments, the one or more therapeutic agents or a pharmaceutical composition thereof described herein can be administered via continuous enteral feeding. In one example, continuous enteral feeding includes administering a pharmaceutical composition directly into the stomach or small intestine of a subject in need thereof via a tube. In other embodiments, a pharmaceutical composition described herein is administered via intermittent or bolus feedings.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3

[0128] Alternatively, or additionally, in some embodiments, one or more therapeutic agents or pharmaceutical compositions thereof can be administered bimonthly, monthly, twice monthly, triweekly, biweekly, weekly, twice weekly, thrice weekly, daily, twice daily, thrice daily, etc., or on another clinically desirable dosing schedule. The dosing regimen for a single subject need not be at a fixed interval, but can be varied over time, depending on the needs of the subject. In some embodiments, an amount of one or more therapeutic agents or pharmaceutical compositions thereof can be administered as a single dose daily.Alternatively, an equivalent amount can be administered in two or more individual doses over a 24-hour period.

[0129] As our experiments have demonstrated, and as we now disclose herein, the benzimidazole and the selenium source (e.g., fenbendazole and L- selenomethionine), and optionally but desirably the praziquantel, may be administered separately but during the same treatment period and / or during the same dosing event, or they may be included in a composition comprising fenbendazole and L- selenomethionine (and optionally but desirably also the praziquantel) in one composition, wherein the treatment period may be any period of time required to stabilize, ameliorate, inhibit, reduce or even resolve the indication, disease, disorder, or condition and / or to stabilize, ameliorate, inhibit, reduce, or even resolve symptoms of the indication, disease, disorder, or condition and may be selected, for example, depending upon the severity of the disease state in a certain patient. For cognitive decline patients as well as early stage Alzheimer’s and Parkinson’s patients, a treatment period may be in a range of from three weeks to six weeks at the doses and / or dosages disclosed herein and below, or may be any period of time required to resolve the disease and / or to resolve symptoms of the disease, with ongoing lifelong maintenance after resolution of the disease and / or disease symptoms at the doses and / or dosages described herein and below. For midstage Alzheimer’s and Parkinson’s patients, a treatment period may be in a range of from five weeks to twelve weeks at the doses and / or dosages disclosed herein and below, or may be any period of time required to resolve the disease and / or to resolve symptoms of the disease, with ongoing lifelong maintenance after resolution of the disease and / or disease symptoms at the doses and / or dosages described herein and below.

[0130] Although no dosage for certain benzimidazoles, such as fenbendazole, in humans is established by the medical community, and furthermore no dosage is established by the medical community for administration of any of either a benzimidazole, a selenium source or praziquantel, let alone the combination of a benzimidazole and a selenium source or the combination of a benzimidazole and a selenium source and praziquantel to treatPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 dementia and dementia conditions and / or diseases such as Alzheimer’s disease(s), Parkinson’s disease(s), Cognitive Decline, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Frontotemporal lobe dementia, and other forms of dementia (hereinafter also aggregately known as “dementia”), especially early and middle stages of these indications, diseases, disorders, and / or conditions, we propose that if one were comparing the doses and dosages we found in experimentation to be highly useful and still safe for treating the indications in comparison to the doses and dosages known for treating canine parasitic infections with the benzimidazole, fenbendazole, that individual doses disclosed herein as well as treatment durations and dose quantities disclosed herein would be considered “massive” or more specifically, “megadoses” or “megadosages” by an ordinary artisan. Likewise, while a safe dose and dosage of the selenium source, L- selenomethionine, is established, the dose and dosage we found efficacious and still safe in our treatment may be multiple times greater than the established dose.

[0131] In other embodiments of the present disclosure, it is anticipated that the indications described herein can be treated by administering to a subject in need thereof with what would be considered megadoses and / or megadosages of fenbendazole alone. However, it is anticipated that the percent of the patient population that can benefit from such a fenbendazole megadose treatment is limited.

[0132] As described in the Example section below, surprisingly, shockingly, contrary to the state of the art and against the widely held belief of those skilled in the art, no negative side effects and no elevated liver enzymes were detected in a healthy 55 year old male human volunteer test subject who orally received the massive doses of fenbendazole described herein, including 4,200 mg of Fenbendazole plus six hundred percent of the established dose of L- selenomethionine (240 mg of L-selenomethionine containing about 1200 mcg of Selenium (elemental)) every other day for 30 consecutive days, followed by a 60 day hiatus, followed again by administration of the 4,200 mg of fenbendazole plus three hundred percent the established dose of L-selenomethionine (120 mg of L-selenomethionine containing about 600 mcg of selenium (elemental)) every other day for 30 consecutive days, at which point the volunteer patients’ blood was drawn and analyzed. During the second 30 consecutive day treatment course, the administration of the Fenbendazole and the L-selenomethionine was also accompanied by administration of 1600 mg of praziquantel every other day during the 30 day treatment course. There were no elevated liver enzymes, no compromise to kidney function, no elevated or abnormal readouts on comprehensive metabolic panel analyses, no other detected negative side effects and no adverse events experienced by this subject. ThesePCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 results are shocking, surprising, against the trend in the industry, contrary to the state of the art and contrary to the widely held belief of those skilled in the field. Furthermore, as described in the examples below, this treatment protocol was demonstrated effective at reversing and curing mid-stage Alzheimer’s disease in a 95 year old male suffering from midstage Alzheimer’s disease in addition to reversing and curing in other patients all of early Alzheimer’s, Cognitive Decline, and Parkinson’s tremors, these results also being shocking, surprising, contrary to the state of the art and against the trend in the industry and contrary the widely held belief of those skilled in the art.

[0133] The present disclosure’s compositions and treatment methods for the indications including but not limited to Alzheimer’s, Parkinson’s, cognitive decline, dementia, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), comprises administration of the following during the treatment period, either in combination such as in a pharmaceutical composition, or administered individually during the treatment period:4200 mg of fenbendazole;240 mg of L- selenomethionine; and, 1,600 mg of praziquantel.

[0134] The above doses of the above therapeutic agents may be administered every day (as may be in a single dose administered during a single 24 hour period) for at least 35 days or until resolution of disease symptoms. For patients who demonstrate sensitivity to the treatment, the present disclosure includes administration of the above as well as of the herein disclosed compositions and substances every other day, or every third day, or every fourth day, or every fifth day, or every sixth day, or every seventh day, until an interval is found at which any indicators of toxicity are deemed acceptable, for at least 35 days, or for at least a total of 35 administrations of the doses, or until resolution of disease symptoms. However, as of the date of this disclosure, none of the experimental subjects exhibited sensitivity to the treatment.

[0135] In other embodiments, any and all doses of the present disclosure’s therapeutic agents or compositions thereof may be administered every day for at least 15 days, at least 30 days, at least 60 days, or until resolution of disease symptoms. For patients who demonstrate sensitivity to the treatment, the present disclosure includes administration of the above therapeutic agents or pharmaceutical compositions thereof every other or every third day for at least 15 days, at least 30 days, at least 60 days, or until resolution of disease symptoms. However, none of the experimental subjects exhibited sensitivity to the treatment.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3

[0136] The present disclosure’s treatment for the indications including, but not limited to, Alzheimer’s disease, Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), Parkinson’s disease cognitive decline, dementia, or frontotemporal lobe dementia can include at least the following dosages of fenbendazole, that may be administered with any of the doses and dosages disclosed herein for any or all of the L- selenomethionine, and for the praziquantel: in a range of between 400 mg to 20,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 800 mg to 20,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 1,600 mg to 20,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 2,000 mg to 20,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 400 mg to 10,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 800 mg to 10,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 16,000 mg to 10,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 2,000 mg to 10,000 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 1600 mg to 5,200 mg per day each day or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved;PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 and may be in a range of between 2000 mg to 5,200 mg per day each or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 2800 mg to 5,200 mg per day each or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 3200 mg to 5,200 mg per day each or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 3800 mg to 5,200 mg per day each or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be in a range of between 4200 mg to 5,200 mg per day each or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be exactly or about 4,500 mg per day each or every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be exactly or about 4,500 mg per day every other day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and may be exactly or about 5,200 mg per day every day for, for example, a 28 to 35 day period and / or until the disease indication is resolved; and optionally may be exactly or about 2,100 mg per day every day for, for example, a 28 to 35 day period and / or until the disease indication is resolved, at which point, a lifelong maintenance dose may be administered to the patient, including as disclosed herein.

[0137] The L-selenomethionine can be administered concurrently and / or in combination with the fenbendazole, at any dosage of fenbendazole including the dosages stated supra, wherein the dosage of L-selenomethionine may be in a range of 50 mg to 400 mg of L-selenomethionine or every other day (and / or so as to provide 250 mcg to 2,000 mcg of selenium (elemental) or every other day, and / or so as to provide 250 mcg to 2,000 mcg of selenium (elemental) or every other day from a source of bioavailable selenium), that, as stated supra, may be administered in combination with and / or administered simultaneously and / or concurrently with administration of the fenbendazole, wherein the dosage of L- selenomethionine and / or wherein the dosage of selenium in a substance containing seleniumPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 and / or a selenium compound (that may be a source of bioavailable selenium) may be administered with any of the doses and / or dosages disclosed herein for any or all of the fenbendazole and the praziquantel, wherein the dosage of selenium and / or wherein the dosage of selenium in a selenium source and / or a selenium compound (that may be a source of bioavailable selenium) may be in a range of:50 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 250 mcg to 2,000 mcg of selenium and / or elemental selenium or every other day);60 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 300 mcg to 2,000 mcg of selenium and / or elemental selenium or every other day);80 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 400 mcg to 2,000 mcg of Selenium and / or elemental selenium or every other day);100 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 500 mcg to 2,000 mcg of Selenium and / or elemental selenium or every other day);120 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 600 mcg to 2,000 mcg of selenium and / or elemental Selenium or every other day);150 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 750 mcg to 2,000 mcg of selenium and / or elemental selenium or every other day);180 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 900 mcg to 2,000 mcg of selenium and / or elemental selenium or every other day);200 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 1,000 mcg to 2,000 mcg of selenium and / or elemental selenium or every other day);240 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 1,200 mcg to 2,000 mcg of selenium and / or elemental selenium or every other day);PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3280 mg to 400 mg of L-selenomethionine or every other day (and / or a selenium compound having 1,400 mcg to 2,000 mcg of selenium and / or elemental selenium or every other day);240 mg to 280 mg of L-selenomethionine or every other day (and / or a selenium compound having 1,200 mcg to 1,400 mcg of selenium and / or elemental selenium or every other day);200 mg to 240 mg of L-selenomethionine or every other day (and / or a selenium compound having 1,000 mcg to 1,200 mcg of selenium and / or elemental selenium or every other day); and200 mg to 240 mg of L-selenomethionine daily (and / or a selenium compound having 1,000 mcg to 1,200 mcg of selenium and / or elemental selenium or every other day), wherein the administration of the L-selenomethionine and / or a selenium compound may be or every day for, for example, a 28 to 35 day period and / or until the disease indication is resolved, and may be daily for, for example, a 28 to 35 day period and / or until the disease is resolved, at which point, usefully, a lifelong maintenance dose is administered to the patient as disclosed below.

[0138] Optionally, in other embodiments of the present disclosure, the present disclosure discloses a treatment comprising administration of fenbendazole and L- selenomethionine, and praziquantel, wherein the doses and dosages of praziquantel may be combined with any and all of the doses and dosages disclosed herein for any or all of the fenbendazole or the L-selenomethionine, wherein the dosage of praziquantel may be in a range of doses of from 600 mg to 2000 mg daily of praziquantel, and may be in doses of from:800 mg to 2000 mg daily or every other day of praziquantel;1000 mg to 2000 mg daily or every other day of praziquantel;1200 mg to 2000 mg daily or every other day of praziquantel;1400 mg to 2000 mg daily or every other day of praziquantel;1600 mg to 2000 mg daily or every other day of praziquantel;1800 mg to 2000 mg daily or every other day of praziquantel; or1,600 mg daily of praziquantel, that presently is disclosed, wherein the administration of the praziquantel is in combination with and / or concurrent with and / or simultaneously with the administration of the fenbendazole and / or of the fenbendazole in combination with the L- selenomethionine, and wherein the administration of the L-selenomethionine may be or every day for, for example, a 28 to 35 day period and / or until the disease indication is resolved, andPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 may be daily for, for example, a 28 to 35 day period and / or until the disease is resolved, at which point, a lifelong maintenance dose may be administered to the patient as disclosed herein, and below.

[0139] Exemplary dosages and administration methods and / or courses for compositions of the present disclosure for use in methods described herein include the administration of any of: the fenbendazole; the fenbendazole in combination with the L- selenomethionine; the fenbendazole in combination with the praziquantel; and / or the fenbendazole in combination with the L-selenomethionine, in combination with the praziquantel, is administered either or every other day at the above disclosed dosages for the first 28 to 35 days of treatment (depending upon the severity of the disease, with mild cases requiring less treatment duration than more severe cases), after which first 28 to 35 days of treatment the dosage levels of all the ingredients may be halved (compared to the dosage levels for the first 28 to 35 days of treatment) for the subsequent and second 28 to 35 days of treatment; after which subsequent and second 28 to 35 days of treatment the dosage levels for all the ingredients may be one third (compared to the dosage levels for the first 28 to 35 days of treatment) for the subsequent and third 28 to 35 days of treatment; after which subsequent and third 28 to 35 days of treatment the dosage levels for all the ingredients may be one fourth (compared to the dosage levels for the first 28 to 35 days of treatment) for the subsequent and fourth 28 to 35 days of treatment; after which subsequent and fourth 28 to 35 days of treatment the dosage levels for all the ingredients may be one fifth (compared to the dosage levels for the first 28 to 35 days of treatment) for the subsequent and fifth 28 to 35 days of treatment; after which subsequent and fifth 28 to 35 days of treatment the dosage levels for all the ingredients may be one sixth (compared to the dosage levels for the first 28 to 35 days of treatment) for the subsequent and sixth 28 to 35 days of treatment, and may be maintained at this dosage level for the remainder of the patient’s life.

[0140] In exemplary embodiments, a presently disclosed composition and method for forming and using the present disclosure and administering the composition either daily, or every other day, or administering the combination of fenbendazole and the L-selenomethionine every other day and administering the praziquantel every other day on the days the composition comprising the fenbendazole and L-selenomethionine is not administered, can include the following active ingredients and / or ingredients: a composition comprising:PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-34200 mg of fenbendazole.240 mg of L- selenomethionine (having 1,200 mcg of Selenium (elemental)); and, 1 ,600 mg of praziquantel. or; a composition comprising:4200 mg of fenbendazole;160 mg of L- selenomethionine (having 800 mcg of Selenium (elemental)); and, 800 mg of praziquantel.

[0141] Another exemplary embodiment of a presently evaluated composition and method of the present disclosure for forming and using the present disclosure comprises the following active ingredients and / or ingredients: a composition comprising:4200 mg of fenbendazole;240 mg of L- selenomethionine; and800 mg of praziquantel.

[0142] Methods in accordance with the present disclosure can further comprise the step of administering a maintenance amount of a benzimidazole, a benzimidazole derivative, a benzimidazole or benzimidazole derivative metabolite, a selenium source, and combinations and pharmaceutical compositions thereof to the subject to prevent relapse of an indication, condition, disease, and / or disorder described above.

[0143] In some embodiments, the maintenance amount of fenbendazole administered to the subject to prevent relapse of an indication, condition, disease, and / or disorder described herein is from about 100 mg to about 1000 mg daily. In particular embodiments, the maintenance amount of the selenium source can be the amount sufficient to provide an assimilable form of selenium that has from about 50 mcg to about 1750 mcg of elemental selenium daily or every other day.

[0144] In further embodiments, a maintenance amount of praziquantel administered to the subject to prevent relapse of an indication, condition, disease, and / or disorder is at least 100 mg, at least 200 mg, at least 300 mg, at least 400 mg, or at least 500 mg of praziquantel is administered or every other day and / or every other dose.

[0145] In an exemplary embodiment, upon resolution of the indication, condition, disease, and / or disorder and / or cessation of the indication, condition, disease, and / or disorder symptoms, the present disclosure includes a treatment comprising a lifelong and / or long termPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 and / or maintenance dose of therapeutic agents either every or every other day for the remainder of the patient’s life and / or for the long term, the dose including:200 to 400 mg of fenbendazole;40 to 80 mg of L-selenomethionine; and,200 to 400 mg of praziquantel.

[0146] A certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:400 mg of fenbendazole;80 mg of L-selenomethionine; and,400 mg of praziquantel.

[0147] Another certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:300 mg of fenbendazole;60 mg of L-selenomethionine; and,300 mg of praziquantel.

[0148] Another certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:200 mg of fenbendazole;40 mg of L-selenomethionine; and,200 mg of praziquantel.

[0149] A certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:200 to 800 mg of fenbendazole;40 to 120 mg of L-selenomethionine; and,0 to 800 mg of praziquantel.

[0150] Another certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:300 mg of fenbendazole;60 mg of L-selenomethionine; and,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3100 mg of praziquantel.

[0151] Another certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:200 mg of fenbendazole;40 mg of L-selenomethionine; and, 50 mg of praziquantel.

[0152] Another certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:300 mg of fenbendazole;60 mg of L-selenomethionine; and,0 mg of praziquantel.

[0153] Another certain presently disclosed life-long and / or long-term maintenance treatment of the present disclosure comprises administration of the following therapeutic agents at the following doses, daily:200 mg of fenbendazole;40 mg of L-selenomethionine; and, 0 mg of praziquantel.

[0154] Fig. 1 is a flow diagram illustrating a method 10 in accordance with the present invention for treating an indication, disease, disorder, or condition described above. The method 10 begins at 20 with the administration of a therapeutically effective amount of a benzimidazole, such as described above, to a subject in need thereof. At 30, a therapeutically effective amount of a selenium source is administered to the subject. At 40, a therapeutically effective amount of praziquantel is optionally (designated by the dotted line) administered to the subject. Finally, at 50, a maintenance amount of the benzimidazole and the selenium source, and optionally the praziquantel, is administered to the subject to prevent relapse of an indication, condition, disease, and / or disorder being treated. In accordance with the method 10, each of the therapeutic agent components may be administered to the subject simultaneously, separately, or in combinations containing two or more of the therapeutic agent components (e.g., in a pharmaceutical composition).

[0155] Fig. 2 is a flow diagram illustrating a method 110 in accordance with the present invention for treating an indication, disease, disorder, or condition described above. The method 110 begins at 120 with the administration of a therapeutically effective amount of aPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 benzimidazole, such as those described above, and a therapeutically effective amount of a source of bioavailable selenium to a subject, such as described above, to a subject in need thereof. At 140, a therapeutically effective amount of praziquantel is optionally (designated by the dotted line) administered to the subject. Finally, at 150, a maintenance amount of the benzimidazole and the selenium source, and optionally the praziquantel, is administered to the subject to prevent relapse of an indication, condition, disease, and / or disorder being treated. In accordance with the method 110, the benzimidazole and the source of bioavailable selenium are administered at about the same time to the subject either administering two separate compositions simultaneously or alternatively in a single pharmaceutical composition containing both agents and optionally including praziquantel or separately administering praziquantel.

[0156] Fig. 3 is a flow diagram illustrating a method 210 in accordance with the present invention for a method of preventing cognitive decline symptoms from manifesting to a level where they are diagnosable in a subject as cognitive decline. The method 210 begins at 220 with the administration of a therapeutically effective amount of a benzimidazole, such as those described above, and a therapeutically effective amount of a source of bioavailable selenium to a subject, such as described above, to a subject in need thereof. At 240, a therapeutically effective amount of praziquantel is optionally (designated by the dotted line) administered to the subject. In accordance with the method 210, the benzimidazole and the source of bioavailable selenium are administered at about the same time to the subject either administering two separate compositions simultaneously or alternatively in a single pharmaceutical composition containing both agents and optionally including praziquantel or separately administering praziquantel.

[0157] Fig. 4 is a flow diagram illustrating a method 310 in accordance with the present invention for a method of treating cancer in a subject. The method 310 begins at 320 with the administration of a therapeutically effective amount of a benzimidazole, such as those described above, and a therapeutically effective amount of a source of bioavailable selenium to a subject. At 340, a therapeutically effective amount of praziquantel is optionally (designated by the dotted line) administered to the subject. In accordance with the method 310, the benzimidazole and the source of bioavailable selenium are administered at about the same time to the subject either administering two separate compositions simultaneously or alternatively in a single pharmaceutical composition containing both agents and optionally including praziquantel or separately administering praziquantelPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3ExamplesHuman Subiect Treatment:

[0158] To evaluate safety, a healthy 55-year-old male volunteer was orally administered compositions of the present disclosure according to treatment methods of the present disclosure as follows:A first 30 day treatment course where the volunteer orally consumed 4,200 mg of Fenbendazole plus six hundred percent of the established dose of L-Selenomethionine (240 mg of L- selenomethionine containing about 1200 mcg of selenium (elemental)) every other day for 30 consecutive days, followed by a 60 day hiatus, followed again by a second 30 day treatment course where the volunteer orally consumed administration of 4,200 mg of fenbendazole plus three hundred percent the established dose of L- Selenomethionine (120 mg of L-selenomethionine containing about 600 mcg of selenium (elemental)) every other day for a second 30 consecutive days, and further orally consumed 1600 mg of Praziquantel every other day on the off days from the Fenbendazole and the L-selenomethionine.

[0159] The volunteer’s blood was drawn within 24 hours of completion of the second 30 day treatment course and analyzed. As summarized in Table 1 below, blood tests indicated that there were no elevated liver enzymes following treatment. As summarized in Table 2 below, blood tests further indicated that there was no compromise to kidney function following the course of treatment. In addition, there were no elevated or abnormal readouts on comprehensive metabolic panel analyses, no other detected negative side effects and no adverse events experienced by this subject.Table 1 (Liver Enzyme Analysis)(ENZ=enzymatic test, COL=colorimetric test)Table 2 (Kidney Function Analysis)PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3formula.(ENZ-enzymatic test, KIN-kinetic method, COL-colorimetric test, and FC-flow cytometry)Treatment of a 95-year-old male mid-stage Alzheimer’s patient:

[0160] The above stated active ingredients were orally consumed by a 95-year-old male mid-stage Alzheimer’s patient in the following protocol:PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3The 4200 mg of Fenbendazole and the 240 mg of L- selenomethionine were orally consumed simultaneously and / or concurrently, every other day, for 33 days, by this 95- year-old male mid-stage Alzheimer’s disease patient. About 2 tablespoons of grass-fed milk butter were consumed by the patient simultaneously with and / or immediately prior to consuming the fenbendazole and L- selenomethionine to promote absorption of the fenbendazole.

[0161] Additionally: Starting at day 30 of treatment, the patient additionally orally consumed 800 mg daily of praziquantel for 15 days.

[0162] No other medications were taken by the patient during the treatment course, and no change was made to the patient’s diet besides addition of the grass-fed milk butter, that was a typical diet for a low-income patient. No vitamins or probiotics were given to or taken by the patient. Other than the administration of the milk butter, the intervention was exclusively pharmacological.

[0163] The patient’s disease symptoms were resolved by day 33 of treatment.Treatment continued at half the original dosage for the next fifty days, and by day 81 the patient experienced remarkable rejuvenation to a healthy state typically associated by much younger healthy males, along with, amazingly, resolution even of his postural stoop, ability to once again rise unaided from sitting on the floor, to once again walk without a cane, along with restoration of previously lost senses of taste and smell, and return to normal of a previously seriously degraded sense of hearing, along with other physical improvements and improved motor coordination.

[0164] The patient also voluntarily remarked that he experienced return of erectile function. The patient experienced no observed negative side effects and no adverse events.

[0165] Of note is that the patient had been a chain smoker up to when he became demented with mid-stage Alzheimer’s, and as treatment commenced the patient recommenced and continues smoking. Therefore, we believe that these compositions and methods are particularly applicable to dementia patients with a history of smoking.

[0166] At day 83, the patient commenced consuming a low-level maintenance dose of the fenbendazole and L-selenomethionine, and the patient’s condition has never deteriorated since day 83 until the writing of this text, that is at around day 223 of treatment. The patient now at day 223 exhibits no sign of dementia and is extremely communicative and active. In fact, it is believed that the treatment disclosed in the present disclosure has promoted regeneration of the patient’s brain tissue and therefore it is further contemplated that the treatment and compositions of the described herein can be successfully used to effectPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 regeneration of brain tissue, or to promote and / or effect regeneration of brain tissue and / or neural tissue and / or nerves and / or spinal tissue in a patient.Treatment of a 70-year-old male with cognitive decline qualifying as early-stage Alzheimer’s:

[0167] In another case, a 70-year-old male with cognitive decline diagnosable as early- stage Alzheimer’s disease orally consumed the following embodiment of the present disclosure and treatment dosage every other day for 4 weeks:2800 mg of fenbendazole;240 mg of L-selenomethionine.

[0168] At the end of the 2ndweek of treatment, the patient additionally orally consumed 800 mg every other day of praziquantel for seven treatment days.

[0169] By the end of the 4- week treatment course the patient experienced full resolution of all cognitive symptoms, with marked rejuvenation by day 60. The patient experienced no observed negative side effects and no adverse events. The patient took no other form of medication for any reason or purpose. There were no modifications of lifestyle or diet, no use of probiotics or vitamins. This was a purely pharmacological intervention. Of note is that the patient was and is a frequent smoker.Three Additional Human Patients

[0170] Three other male patients underwent the same treatment protocol as described above for the 70-year-old male, where each of the three additional male patients exhibited cognitive decline diagnosable as early-stage Alzheimer’s disease, in addition to other symptoms as mentioned immediately below, with the same excellent outcome as for the 70- year-old male:One patient was a 76-year-old male exhibiting symptoms diagnosable as early Alzheimer’s and early Parkinson’s, as well as known symptoms diagnosable as early Frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), all of which were fully resolved at the completion of treatment. The patient did not continue with any maintenance treatment and long term outcome is unknown.The two other patients were a 57-year-old male and a 53-year-old male, each with known symptoms diagnosable as early Alzheimer’s and early Parkinson’s, that was fully resolved. In all cases there were no negative side effects observed and no adverse events.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3Treatment of Cancer Patients:

[0171] As a result of the positive safety data obtained with and in respect to the 55 year old healthy male human volunteer referenced herein and above, in addition to the positive results obtained with respect to the other human patients referenced herein and above, we anticipate that the compositions and methods of the present disclosure are particularly likely to result in a major breakthrough in cancer treatment by rendering in particular fenbendazole safe enough to use in doses and dosages that well exceed the known doses and dosages for use of fenbendazole as a cancer treatment. In particular, because we have demonstrated in our human trials that our composition and methods that comprise administration of fenbendazole with a bioavailable selenium source, and in particular L-selenomethionine, appears to have the effect of rendering fenbendazole safe and in particular non-hepatoxic in doses and dosages that are well in excess of one hundred percent and even in excess of four hundred percent the doses and dosages of fenbendazole that we are aware of as having been used when fenbendazole is administered to human patients as an adjunct therapy or even as a monotherapy for cancer, it is anticipated that, usefully, administration of the composition of the present disclosure and administration of the methods of the present disclosure may be of particular use in treating cancer and / or in preventing cancer, in particular when combining a benzimidazole, benzimidazole derivative and / or metabolite with a source of selenium, especially a source of bioavailable selenium, and in particular when the benzimidazole is fenbendazole, and also in particular when the selenium source is L-selenomethionine. If we are correct, as anticipated, this would be a major breakthrough in cancer treatment, where investigation of administration of much greater doses of fenbendazole compared to what is currently commonly administered in cancer therapy and / or treatment is currently hampered by concerns of toxicity including hepatoxicity experienced by some patients who received during cancer treatment fenbendazole at doses and dosages that are several fold lesser than the doses and dosages of fenbendazole used in forming compositions of the present disclosure and / or used in methods of the present disclosure.

[0172] We believe and anticipate that compositions and methods of the present disclosure make it possible to safely administer fenbendazole at doses and dosages of the present disclosure when the doses and dosages of fenbendazole disclosed herein form compositions of the present disclosure and / or form agent(s) of the methods of the present disclosure. We further anticipate the doses and dosages of fenbendazole in the compositions and methods of the present disclosure, such as doses shown to be safe in a control subject,PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 shall show a greatly enhanced therapeutic effect in the treatment and / or prevention of cancer(s), while concurrently being sufficiently safe to administer to human patients. Such results, specifically that it is possible to safely administer the doses and dosages of fenbendazole, in any form and in any manner, at much higher doses and dosages than currently known for treating cancer, would be against the state of the art and contrary to the widely held belief of those skilled in the art that fenbendazole presents a serious toxicity risk at the doses it is known at for use in cancer treatment, that axiomatically means it presents an even more serious toxicity risk at the much higher doses disclosed in the compositions and methods of the present disclosure.

[0173] We believe and anticipate that, to evaluate the safety and therapeutic efficacy of the administration of fenbendazole in combination with L-selenomethionine, non-small cell lung cancer (NSCLC) patients diagnosed with either adenocarcinoma (alveolar cell carcinoma) or large-cell lung carcinoma may be orally administered compositions of the present disclosure according to treatment methods of as follows:

[0174] A first 30 day treatment course where the patient orally consumes 4,200 mg of Fenbendazole plus six hundred percent of the established dose of L-Selenomethionine (240 mg of L-selenomethionine containing about 1200 mcg of selenium (elemental)) every other day for 30 consecutive days, followed by a 30 day hiatus, followed again by a second 30 day treatment course where the volunteer orally consumes administration of 4,200 mg of fenbendazole plus three hundred percent the established dose of L-Selenomethionine (120 mg of L-selenomethionine containing about 600 mcg of selenium (elemental)) every other day for a second 30 consecutive days, and some patients further orally consume 1600 mg of Praziquantel every other day on the off days from the Fenbendazole and the L- selenomethionine. We anticipate that each patient’s blood may suitably be drawn within 24 hours of completion of the second 30 day treatment course and analyzed and compared to samples taken prior to the course of treatment, where the blood tests would be performed to indicate whether there are elevated liver enzymes indicative of hepatoxicity in the patient following treatment. We further anticipate that additional blood tests would be performed to determine whether kidney function is compromised following the course of treatment. Comprehensive metabolic panel analyses on patient blood samples are also anticipated as suitable to perform to determine the presence of elevated or abnormal readouts compared to control values.

[0175] Given the results in our 55 year old healthy male control subject, we anticipate blood tests will fail to detect negative liver and kidney function side effects and that noPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 serious adverse events will be experienced by the patients during or after the courses of treatment. We further anticipate that the large doses of fenbendazole administered during the course of treatment described above will result in a reduced observed tumor growth, tumor size and weight, and / or apoptotic cancer cell death, especially since similar anticancer effects have been reported in in vitro and in vivo animal model studies using fenbendazole alone at significantly smaller doses for much shorter durations (e.g., 1 mg every second day for 12 days). In human patients exhibiting no elevated liver enzymes indicative of hepatoxicity, we anticipate that the administration of the fenbendazole and the L- selenomethionine taken from the example immediately above may be every day instead of every other day. In patients continuing to exhibit no elevated liver enzymes indicative of hepatoxicity after increasing the dosage to every day instead of every other day, we anticipate that the hiatus may be changed to 15 days instead of 30 days. In patients continuing to exhibit no elevated liver enzymes indicative of hepatoxicity after a 30 day regimen of the fenbendazole and the L- selenomethionine daily and a hiatus of 15 days, we anticipate that: the dose of fenbendazole may be increased to 5,600 mg, or to 7,500 mg, or to 10,000, or to greater than 10,000 mg, without a hiatus, until evidence is detected of elevated liver enzymes indicative of hepatoxicity, at which point the dose of fenbendazole may be reduced to the last used dose that did not generate elevated liver enzymes indicative of hepatoxicity, at which point the treatment may continue without a hiatus until the disease symptoms are resolved and / or resolved to the satisfaction of the patient and / or medical provider; or may continue with 30 day treatment courses interspersed with 30 day hiatuses; or, the dosage may be changed to every other day, or every third day, or every fourth day, or every fifth day, without a hiatus, while retaining the highest dose of fenbendazole that first exhibited elevated liver enzymes indicative of hepatoxicity until there is no longer evidence of elevated liver enzymes indicative of hepatoxicity (in such emobdiments, the L- selenomethionine may be dosed at a maximum of 280 mg each time the fenbendazole is dosed).

[0176] However, in patients exhibiting elevated liver enzymes indicative of hepatoxicity, we anticipate that: the dose of the 4,200 mg of fenbendazole and the 240 mg of L-selenomethionine may be dosed every third day, or every fourth day, or every fifth day, and so on, without cessation at a certain number of calendar days, and without a hiatus, where the interval of days may be selected by monitoring the patient and determining at which dosage regimen the patient exhibits no elevated liver enzymes indicative of hepatoxicity, at which point the treatment may continue without a hiatus until the disease symptoms are resolved and / or resolved to the satisfaction of the patient and / or medical provider.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3

[0177] From the above description of the invention, those skilled in the art will perceive improvements, changes and modifications. Such improvements, changes and modifications within the skill of the art are intended to be covered by the appended claims. All references, publications, and patents cited in the present application are herein incorporated by reference in their entirety. l

Claims

PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3Having described the invention, we claim:

1. A pharmaceutical composition for the treatment or prevention of an indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, or for the treatment or prevention of cancer, the pharmaceutical composition comprising: a benzimidazole, benzimidazole derivative, or a metabolite thereof; and a selenium source.

2. The pharmaceutical composition of claim 1, wherein the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, flubendazole, ciclobendazole, thiabendazole, and combinations thereof.

3. The pharmaceutical composition of claim 1, wherein the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, and combinations thereof.

4. The pharmaceutical composition of claim 1, wherein the benzimidazole comprises fenbendazole.5 The pharmaceutical composition of any one of the preceding claims, wherein the selenium source is a bioavailable selenium source.

6. The pharmaceutical composition of any one of the preceding claims, wherein the selenium source is a source of bioavailable selenium selected from the group consisting of selenomethionine, selenocystine, sodium selenite, sodium selenate, methylselenocysteine, selenium glycinate, and a selenium nanoparticle.

7. The pharmaceutical composition of any one of the preceding claims, wherein the selenium source comprises L- selenomethionine.

8. The pharmaceutical composition of any one of the preceding claims, wherein the composition further comprises praziquantel.

9. The pharmaceutical composition of any one of the preceding claims, wherein the composition further comprises a pharmaceutically acceptable carrierPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-310. The pharmaceutical composition of claim 9, wherein the composition is formulated as an oral dosage form.

11. The pharmaceutical composition of claim 10, wherein the oral dosage form comprises a suspension.

12. The pharmaceutical composition of any one of claims 2 to 11, wherein the composition comprises at least 2000 mg of the benzimidazole.

13. The pharmaceutical composition of any one of claims 2 to 11 , wherein the composition comprises at least 4000 mg of the benzimidazole.

14. The pharmaceutical composition of claims 12 to 13, wherein the benzimidazole is fenbendazole.

15. The pharmaceutical composition of claims 8 to 14, wherein the composition comprises at least 800 mg of praziquantel.

16. The pharmaceutical composition of claims 8 to 14, wherein the composition comprises at least 1600 mg of praziquantel.

17. A method of treating or preventing an indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, or cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising: a benzimidazole, benzimidazole derivative, or a metabolite thereof; a selenium source; and a pharmaceutically acceptable carrier.

18. The method of claim 17, wherein the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, flubendazole, ciclobendazole, thiabendazole, and combinations thereof.

19. The method of claim 17, wherein the benzimidazole is selected from the group consisting of fenbendazole, mebendazole, albendazole, and combinations thereof.

20. The method of claim 17, wherein the benzimidazole comprises fenbendazole.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-321. The method of any one of claims 17 to 20, wherein the selenium source is a source of bioavailable selenium.

22. The method of claim 21, wherein the selenium source is a source of bioavailable selenium selected from the group consisting of selenomethionine, selenocystine, selenite, selenate, methylselenocysteine, selenium glycinate and a selenium nanoparticle.

23. The method of claim 21, wherein the selenium source comprises L-selenomethionine.

24. The method of any one of claims 17 to 23, wherein the indication is cognitive decline, dementia, Parkinson’s disease or Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), or wherein the cancer is a solid tumor type.

25. The method of any one of claims 17 to 23, wherein the indication is cognitive decline, dementia, Parkinson’s disease or Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), or wherein the cancer is breast cancer, lung cancer, prostate cancer, pancreatic cancer, cancers of the brain, brain tumors, brain cancer and other nervous system cancer, esophageal cancer, liver cancer and / or intrahepatic bile duct cancer, acute myeloid leukemia, stomach cancer, myeloma, laryngeal cancer, anaplastic thyroid cancer, colorectal cancer, Non- Hodgkin Lymphoma, or ovarian cancer.

26. The method of any one of claims 17 to 23, wherein the dementia is Alzheimer’s disease, or wherein the cancer is selected from the group consisting of non-small cell lung cancer (NSCLC), melanoma, cervical cancer, colorectal cancer, leukemia, hepatocellular carcinoma, estrogen receptor positive (ER+) breast cancer and triple negative breast cancer (TNBC)27. The method of any one of claims 17 to 26, wherein the therapeutically effective amount is the amount required to ameliorate at least one symptom of the indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder, and / or of the cancer.

28. The method of any one of claims 17to 27, wherein the subject is treated until the cancer has been resolved and / or until resolution of the indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder.

29. The method of any of claims 17 to 28, further comprising the step of administering a maintenance amount of the pharmaceutical composition to the subject to prevent relapse ofPCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-3 the cancer and / or to prevent the relapse of the indication selected from, Alzheimer’s disease, Parkinson’s disease, Frontotemporal dementia (FTD) and / or frontotemporal lobar degeneration (FTLD), dementia, cognitive decline, neural injury, neurodegeneration, and / or a neurodegenerative and / or neuropsychiatric condition, a neurodegenerative and / or neuropsychiatric disease, and / or a neurodegenerative and / or neuropsychiatric disorder.

30. The method of claim 29, wherein the maintenance amount of fenbendazole is from about 100 mg to about 1000 mg daily.

31. The method of claims 29-30, wherein the maintenance amount of the selenium source is sufficient to provide an assimilable form of selenium that includes from about 50 mcg to about 1750 mcg of elemental selenium daily or every other day.

32. The method of any one of claims 17-31, wherein the therapeutically effective amount of the selenium source in the composition administered to the subject is the amount required to reduce toxicity of the benzimidazole, benzimidazole derivative, or a metabolite thereof, to non-cancerous cells of the subject.

33. The method of any one of claims 17-32, wherein the pharmaceutical composition is formulated as an oral dosage form.

34. The method of claim 33, wherein the oral dosage form comprises a suspension.

35. The method of any one of claims 17-34, wherein the subject is a human.

36. The method of any one of claims 17-35, wherein from about 400 mg to 20,000 mg of the benzimidazole is administered daily or every other day.

37. The method of any one of claims 17-35, wherein from about 2,800 mg to 10,000 mg of the benzimidazole is administered daily or every other day.

38. The method of any one of claims 17-35, wherein from about 2,800 mg to 5,200 mg of the benzimidazole is administered daily or every other day.

39. The method of any one of claims 17-35, wherein from about 4,500 mg to 5,200 mg of the benzimidazole is administered daily or every other day.

40. The method of claims 36 to 39, wherein the benzimidazole is fenbendazole.

41. The method of any one of claims 21-40, wherein from about 250 mcg to about 10 mg of bioavailable elemental selenium is administered daily or every other day.

42. The method of any one of claims 21-40, wherein from about 600 mcg to about 7.5mg of bioavailable elemental selenium is administered daily or every other day.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-343. The method of any one of claims 21-40, wherein from about 1200mcg to about 7.0 mg of bioavailable elemental selenium is administered daily or every other day.

44. The method of any one of claims 17-28 or 33-43, wherein the pharmaceutical composition further comprises praziquantel.

45. The method of claim 44, wherein at least 800 mg of praziquantel is administered daily or every other day.

46. The method of claim 44, wherein at least 1600 mg of praziquantel is administered daily or every other day.

47. The method of any one of claims 17-25 or 29-43, wherein the pharmaceutical composition further comprises praziquantel.

48. The method of claim 47, wherein at least 100 mg of praziquantel is administered daily or every other day and / or every other dose.

49. The method of claim 47, wherein at least 400 mg of praziquantel is administered daily or every other day and / or every other dose.

50. The method of claim 44, wherein a dose of praziquantel is about 800 mg.

51. The method of claim 50, wherein the dose of praziquantel is administered daily or every other day.

52. The method of any one of claims 21-40, wherein a dose of elemental selenium is in a range of from about 250 mcg to about 10 mg of bioavailable elemental selenium.

53. The method of claim 50, wherein the dose of elemental selenium is administered daily or every other day.

54. The method of any of claims 20-28, 33-345, or 40-51, wherein a dose of fenbendazole is a range of from about 400 mg to about 5,000 mg.

55. The method of claim 54, wherein the dose of fenbendazole is administered daily or every other day.

56. The method of claim 27, wherein the therapeutically effective amount is the amount required to ameliorate at least a majority of symptoms of the indication and / or all symptoms of the cancer.

57. The method of claim 17, further comprising administering a therapeutically effective amount of an additional anticancer agent or therapy to the subject.PCT / US25 / 44424 02 September 2025 (02.09.2025)Atty Docket No.: SAS-033871 WO ORD-358. The method of claim 32, wherein the non-cancerous cells include hepatocytes.

59. The method of any one of claims 17 to 58, wherein the method further comprises administration of at least one vehicle so as to improve the solubility of a benzimidazole, benzimidazole derivative, or a metabolite thereof or composition thereof when administered to a subject.

60. The method of any one of claims 17 to 59, wherein the method further comprises administration of a therapeutically effective amount of at least one pharmaceutically acceptable antiviral agent or compound.

61. The composition of any one of claims 1 to 16, wherein the composition further comprises a therapeutically effective amount of at least one pharmaceutically acceptable antiviral agent or compound.

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