What changed in this filing

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Item 1. Business

2018-05-01 compared with 2017-04-28 · 218 added, 248 removed, 302 unchanged (61% of the section changed)

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General Overview

We are a development stage pharmaceutical company.

We are a development stage pharmaceutical and nutraceutical company.

We were incorporated in the Province of British Columbia, Canada under the name “649186 B.C.

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Inc., our wholly owned subsidiary, IndUS and Sindu Research Laboratories Pvt Ltd.

As consideration for the purchase, we issued 4,512,500 shares of common stock on November 23, 2015 and 237,500 shares of common stock on December 4, 2015.

We will also be granting 41,833 stock options pursuant to the Agreement and Plan of Merger.

As consideration for the purchase, we issued 4,512,500 shares of common stock on November 23, 2015 and 237,500 shares of common stock on December 4, 2015 and granted 41,833 stock options pursuant to the Agreement and Plan of Merger.

As part of the acquisition, we appointed Dr.

Pravin Chaturvedi as our new Chief Executive Officer and Director.

IndUS is an emerging United States-India cross-border pharmaceutical company located in the Greater Boston area, which is engaged in conducting research and development activities for advancing novel therapeutics in the areas of oncology, infectious diseases and diabetes.

On September 11, 2017, we completed an exchange agreement whereby we exchanged with Dr.

Chaturvedi 100% of its shares of common stock of IndUS and IndUS net liabilities for 3,800,000 shares of common stock of Pivot, upon which Dr.

Chaturvedi resigned as Chief Executive Officer and Director.

On September 12, 2017, we entered into a licensing agreement with Altum Pharmaceuticals Inc.

(“Altum”) whereby we were granted worldwide rights to BiPhasix Transdermal Drug Delivery Technology (“BiPhasix Technology”) for the delivery and commercialization of cannabinoids, cannabidiol (“CBD”), and tetrahydrocannabinol (“THC”) based products.

Financial consideration included:

Issuance of 2,500,000 shares of common stock on effective date of agreement

Issuance of 2,500,000 shares of common stock of Pivot upon Health Canada Natural Product Number (“NPN”) approval;

Royalties on annual gross sales;

For pharmaceutical products, milestone payments payable upon first Investigative New Drug Approval, upon positive outcome of Phase II trial in first indication, and upon New Drug Application approval.

On September 23, 2017, we entered into a collaboration and license agreement with SolMic GmbH (“Solmic”) whereby we will acquire worldwide rights to Solmic’s Solubilisation Technology for the development and commercialization of cannabinoid-containing natural extracts.

Milestones include payments upon the following developments:

1) Regulatory approval of a natural health product;

2) First approval of an investigative new drug application for a pharmaceutical product;

3) Positive outcome of a Phase II clinical trial of a pharmaceutical product in the first indication;

and 4) Approval of a New Drug Application for a pharmaceutical product by the US Food and Drug Administration.

Other consideration include a sales milestone upon aggregate net sales of $5,000,000 and royalties on aggregate net sales.

On December 19, 2017, we commenced trading on the Canadian Securities Exchange under the symbol "PVOT".

On February 28, 2018, we completed the acquisition of ERS Holdings, LLC (“ERS”) pursuant to an Exchange Agreement dated as of February 10, 2018 among Pivot Pharmaceuticals Inc.

("Pivot"), ERS and the members of ERS.

As consideration for the purchase, we paid $333,333 in cash on closing and will pay an additional $333,333 six and twelve (12) months after closing for total cash payment of $1 million.

In addition, we also issued 5,000,000 shares of our common stock and will pay royalties on future net sales.

ERS has developed a patented technology called “RTIC” Ready-To-Infuse-Cannabis, relating to the transformation of cannabis oil into powder for infusion into a variety of food and beverage products such as capsules, K-Cups, stick packs, baked mixes, liquid shots, protein shakes, topicals, lotions, and bottled beverages.

On March 2, 2018, we completed the acquisition of Thrudermic, LLC (“Thrudermic”) and worldwide rights to Thrudermic’s patented Transdermal Nanotechnology for the development and commercialization of transdermal cannabinoids pursuant to an Exchange Agreement dated as of March 2, 2018 among Pivot, Dr.

Joseph Borovsky, Dr.

Leonid Lurya and Thrudermic.

As consideration for the purchase, we paid $1 in cash on closing and issued 500,000 shares of our common stock.

Our principal executive office is located at 1275 West 6th Avenue, Vancouver, B.C.

Canada V6H 1A6, with another office at 25 Olympia Avenue, Suite K-300, Woburn, MA 01801, USA.

Canada V6H 1A6.

Our telephone number is (604) 805-7783.

Our Current Business

We are a development stage biopharmaceutical company engaged in the development and commercialization of therapeutic pharmaceutical products, focused on the strategy of identifying new therapeutic treatments to address unmet medical needs in women’s health including but not limited to urological and/or gynecological disturbances;

and advancing novel anticancer drug candidates to provide new treatment options for metastatic cancers in women that do not have adequate treatment options or have poor response to existing treatment options due to inherent or acquired mutations.

Our research and development activities are focused on i) advancing novel drug candidates for the treatment of women’s cancers including, but not limited to metastatic endometrial cancer and triple-negative breast cancer, which have limited treatment options;

and ii) leveraging novel drug delivery treatment options to allow ‘targeted’ delivery of drugs to address women’s health needs in urological and/or gynecological indications, and iii) opportunistically in-licensing later-stage drug candidates to augment our drug pipeline.

Where appropriate, we intend to depart from these strategies to opportunistically acquire additional novel treatment options to address unmet or under-served medical needs in women’s health.

Our business model currently includes the following activities:

identifying novel drug delivery technologies that will allow targeted drug delivery for drugs;

securing and developing intellectual property rights to such products;

conducting appropriate laboratory tests and clinical trials;

advancing novel drug candidates to treat women’s cancers from our acquisition of IndUS to support Investigational New Drug application to allow first-in-human trials;

opportunistically acquiring later-stage drug candidates that provide new treatment options to address unmet medical needs in women’s health in cancer and lower urinary tract symptoms;

establishing partnerships with large and specialty pharmaceutical companies and/or biotechnology companies to collaboratively develop and/or commercialize our products.

One of our areas of focus includes developing therapeutic applications for existing drugs using novel delivery technologies for the treatment of diseases and conditions specific to cancer and/or urological disturbances in women.

The diseases and conditions that are the subject of our research and development program include addressing resistant cancers affecting women’s health and developing new treatment options using novel drugs and/or novel delivery approaches to address oncological and urological conditions such as various gynecological and breast cancers as well as lower urinary tract symptoms such as overactive bladder.

Our current pipeline addresses the therapeutic areas of cancer and lower urinary tract symptoms (LUTS):

Metastatic endometrial cancer (PVT-005)

Triple-negative breast cancer (PVT-006)

PVT-005 and PVT-006 are novel and patented anticancer small molecule drug candidates acquired through the acquisition of IndUS.

These molecules are novel DNA damage response inhibitors and belong to the chemical class of pyrrolobenzodiazepine dimers (PBDs).

These molecules have shown preclinical activity in cancers that have mutations in their tumor suppression and/or DNA repair abilities and have shown ‘synthetic lethality’ when dosed as monotherapy in such resistant cancers and/or in combination with standard-of-care drugs that are used in chemotherapeutic regimens for such patients.

PVT-005 and PVT-006 have shown excellent activity in tumor cells that have genetic or epigenetic mutations in DNA mismatch repair (mlh1, MSH2), tumor suppression functions (p53, PTEN) and/or homologous recombination (HR) functions.

They have shown significant synergies with platinum-based drugs such as cisplatin, and other drugs like topoisomerase II and I inhibitors (doxorubicin and camptothecin, respectively) and receptor tyrosine kinase (RTK) inhibitors – all or some of which are part of standard-of-care chemotherapeutic regimens to treat ovarian, breast, colorectal, non-small cell lung and other cancers that affect women’s health.

Our research and development strategy is focused on developing novel treatment options to address various unmet medical needs in women’s health, including but not limited to urological issues and breast and gynecological cancers such as metastatic endometrial or triple-negative breast cancer that have inherent or acquired mutations rendering them resistant to existing treatment options and represent orphan drug designation opportunities.

Our management has prioritized the development of the two novel and patented anticancer drug candidates (PVT-005 and PVT-006) focused on the treatment of metastatic endometrial cancer and/or basal-like triple-negative breast cancers (BL-TNBC) in women.

These two indications affect approximately 50,000 and 40,000 women in the United States, respectively, and potentially represent orphan drug indications, that have limited treatment options.

PVT-005 and PVT-006 will be added to standard chemotherapeutic regimens that are used to treat these cancers and as such are intended to augment the regimen and - provide additional benefit to patients that are either refractory or have relapsed following chemotherapy.

Furthermore, due to the novel mechanism of action of these novel PBD candidates, the patients are segmented according to their DNA repair mutations, thus potentially allowing a more “personalized” medical treatment option for these patients.

We will also evaluate novel drug delivery treatment options to allow more targeted and specific delivery options for its novel anticancer drug portfolio and/or for existing drugs that may be amenable to targeted delivery, thus providing a superior benefit;

risk opportunity for these patients.

To date, we have concentrated our research and development (R&D) activities on development of our novel anticancer drug candidates (PVT-005 and PVT-006) for the treatment of metastatic endometrial and/or basal-like triple-negative breast cancers.

We have outsourced all research and development work to third parties, including clinical trial planning, laboratory services, data management, statistical services and report writing.

We anticipate that we will continue to rely on third parties to satisfy our research and development requirements until such time as it becomes cost effective to hire employees to satisfy those requirements.

We have not carried on any research and development activities since January 2009 and our ability to continue our research and development activities depends on securing additional financing.

Our planned research and development for the next 12 months will focus on development activities for PVT-005 and PVT-006 to support the filing of an Investigational New Drug application to initiate first-in-human clinical trials as well as explore novel delivery and/or new therapeutic options for various drugs to address unmet medical needs in urological and/or gynecological disturbances in women.

We will also be required to complete additional steps in order to market and sell any of our products to the public.

Our determination of which specific additional steps we will need to complete before any of our products become marketable may vary depending on the results of the clinical trials and studies mentioned above.

The following table sets out the various steps we anticipate we must complete in order to carry out our business plan for our planned products.

Completion times have been indicated where estimable, as has any progress made to date.

Anticipated Steps

Intellectual Property

Patents issued in the US and other countries on composition of matter, methods of use for treatment of cancers and process of manufacture of the drugs.

Secure Rights to Drugs

Pre-Clinical Testing

Significant nonclinical toxicity studies required for both drugs

Secure Investigational New Drug (“IND”) Approval or Equivalent

Targeted IND filing in the 2 nd half of 2017

Phase I Clinical Trials

Conducted in cancer patients

Phase II Clinical Trials

Required in selected cancer patients

Phase III Clinical Trials

Submit New Drug Application or

Equivalent and Obtain Marketing

Finance Marketing and

Manufacturing of Approved Drug or

Secure Marketing and Manufacturing

Our Research and Development Strategy

Our experienced management team has implemented a business-minded and cost-conscious approach to product research and development by focusing on development of novel therapies to address unmet needs in women’s health.

Our research and development strategy will develop novel delivery options for new and/or existing drugs to address needs in women’s health as well as advance some of its patented and proprietary novel anticancer drugs in gynecological and/or breast cancers through its recent acquisition of IndUS.

In order for a drug to be successful, it must be both efficacious and acceptably safe.

Before a drug may be commercially marketed, it must be scrutinized and approved by applicable health authorities (such as the Food and Drug Administration (“FDA”) in the United States) in each country or jurisdiction where it is sought to be sold.

In pharmaceutical research and development, clinical trials are conducted to allow safety and efficacy data to be collected for new drugs or devices.

Health authorities then scrutinize the clinical trial results and determine, based on the results, whether a drug may be sold to the public.

Similarly, clinical trials may only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and approval to conduct the trials has been granted by the health authority in the country where the trial is scheduled to take place.

Pivot Pharmaceuticals Inc.

is a biopharmaceutical company engaged in the development and commercialization of therapeutic pharmaceuticals and nutraceuticals using innovative drug delivery platform technologies.

Our company focuses on pharmaceutical development of proprietary drug delivery technologies for multiple indications using small molecules, biological and botanical (e.g.

cannabinoids) products to treat unmet medical needs.

During our year ended January 31, 2018, we in-licensed a patented topical transdermal drug delivery technology platform, BiPhasix, and an oral drug delivery technology, Solmic Micelle, for delivery of cannabinoids.

Subsequent to January 31, 2018, we have also acquired the Thrudermic Transdermal Nanotechnology (transdermal) and the Ready-To-Infuse Cannabis technology.

Our fully-owned subsidiaries, Pivot Green Stream Health Solutions Inc.

(“PGS”) and Pivot Naturals, LLC (“Pivot Naturals”) (formerly, ERS), acquired subsequent to January 31, 2018, focus on the research, development, and commercialization of cannabinoid based nutraceuticals.

PGS will generate data to support the safety and efficacy of cannabinoids as Natural Health Product (“NHPs”) as outlined in Health Canada Regulations in order to make particular health claims.

Health Canada publishes the Natural Health Products Regulations (“NHPR”) which set out the requirements governing the sale, manufacture, packaging, labelling, importation, distribution and storage of NHPs.

According to Health Canada, the objective of the NHPR is to provide reasonable assurance that products offered for sale in Canada are safe, efficacious and of high quality.

PGS may also follow applicable and harmonized regulations for product development and commercialization in the US, European Union and Asia Pacific regions.

Alternatively, PGS will commercialize certain cannabinoid products with a Licensed Producer and/or Licensed Distributor as per the regulations concerning Access to Cannabis for Medical Purposes Regulations (“ACMPR”) since certain active ingredients in cannabinoids remain restricted until new legislation permits ease of development and distribution in 2018.

Lastly, PGS may also develop products containing cannabinoid active ingredients obtained from industrial hemp according to the Industrial Hemp Regulations (“IHR”) permitting such products provided they are sourced from industrial hemp.

Otherwise stated, this means that the plants and plant parts of the genera Cannabis, the leaves and flowering heads of which do not contain more than 0.3% THC w/w, and includes the derivatives of such plants and plant parts.

PGS’s pipeline targets indications such as cancer supportive care, pain and inflammation, women’s sexual dysfunction, dermatology and eye disease.

Our overall strategy includes the following:

Acquire market-ready natural health products from third-parties for rebranding and re-sale;

Acquire cannabinoid-based food additives for medical consumer sales;

Develop cannabinoid-based natural health products using our BiPhasix topical platform technology;

Develop pharmaceutical products delivered using our BiPhasix topical platform technology;

Obtain partnerships with Health Canada approved Authorized Licensed Producers and/or Licensed Distributors, which can provide restricted and non-restricted cannabinoids as per the ACMPR or the IHR;

Acquire novel proprietary drug delivery technologies, for example, metered dose, intra-nasal, suppositories;

Make an application at the appropriate time to acquire Health Canada’s Authorized Licensed Producers and Licensed Dealers licenses as per the ACMPR;

Out-license our platform technologies to Licensed Producers or Licensed Distributors and other drug developers;

Secure and develop further intellectual property;

Opportunistically acquire later stage drug candidates that provide new treatment options to address unmet medical needs in health care;

Establish partnerships with large and specialty pharmaceutical companies and/or biotechnology companies to collaboratively develop and/or commercialize our products.

Our Research and Development Strategies

Our management team has implemented a business minded and cost conscious approach to product research and development by focusing on development of novel therapies to address unmet needs in health care.

Our research and development strategy will apply novel drug delivery options for new and/or existing drugs or NHPs.

For a drug to be successful it must be both efficacious and acceptably safe.

Before a drug may be commercially marketed, it must be scrutinized and approved by applicable health authorities (such as Health Canada and the FDA in the United States) in each country or jurisdiction where it is sought to be sold.

In pharmaceutical research and development, clinical trials are conducted to assess the safety and efficacy of the drug and the data to be collected for such new drugs.

Health authorities then scrutinize the pre-clinical and clinical data and determine, based on the results, whether a drug may be sold to the public.

Similarly, clinical trials can only take place once satisfactory information has been gathered on the quality of the product and its non-clinical safety, and approval to conduct clinical trials has been granted by the appropriate health authority in the country where the trial is scheduled to take place.

Clinical trials involving new drugs are commonly classified into four phases.

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Furthermore, approval rates for new drugs at each clinical trial stage are prohibitively low, which may require the sponsor to finance additional trials or abandon the drug under development altogether.

Our research and development strategy includes the development of novel anticancer drugs targeting subsets of women’s cancer patients that have metastatic endometrial, triple-negative breast and/or ovarian cancer, to explore the opportunity of securing an orphan drug designation (intended for patient populations <200,000 in the US).

Since our anticancer portfolio has novel drugs that will require the conduct of nonclinical and clinical studies for new molecular entities (NMEs);

we will also use targeted delivery options for approved (generic) drugs to avoid the higher cost of repeating one or more pre-clinical or clinical, safety, pharmacokinetic or other tests by applying novel drug delivery approaches to get targeted delivery of drugs and get a quicker time to market by leveraging a US regulatory pathway termed 505b2 applications.

In doing so, a company may reduce the time required to complete the necessary research and development activities, which can typically take in excess of ten years, by more than half, as well as reduce the corresponding development costs.

Our recent acquisition of Greater Boston-based IndUS has provided us with a portfolio of novel, patented and proprietary, novel anticancer drug candidates from multiple chemical classes of molecules referred to as pyrrolobenzodiazepine dimers (PBDs).

These molecules have shown excellent anticancer potential during their initial biological testing conducted at the National Cancer Institute in Bethesda, MD.

Subsequent to their initial biological evaluation, chemical scale-up and formulation studies were conducted to evaluate their pharmacokinetics in rats and two novel and patented pyrrolobenzodiazepine dimers were prioritized for advancement through preclinical studies to support first-in-human studies.

PVT-005 and PVT-006 provide novel treatment options in combination with existing chemotherapeutic regimens to address unmet medical needs in women’s cancers.

Our initial focus for PVT-005 is in patients with metastatic endometrial cancer, which harbors microsatellite (genomic) instability in DNA replication and repair pathways that render the cancer resistant to many existing chemotherapy options.

It is estimated that approximately 43,000 women in the United States have metastatic endometrial cancer that would become eligible for new therapy options following their initial treatments and PVT-005 will be added to the standard chemotherapeutic regimen(s) that will be used to treat metastatic endometrial cancer.

Similarly, PVT-006, a novel and patented pyrrolobenzodiazepine dimer, distinct from PVT-005, has been identified as a lead candidate to address unmet medical needs of women with triple-negative breast cancer.

Triple-negative breast cancer is a very aggressive form of breast cancer that affects younger women, predominantly of African-American descent.

It is estimated that approximately 170,000 women in the United States have triple-negative breast cancer.

Five different molecular subtypes of triple-negative breast cancer have been identified and the basal-like subtype of triple-negative breast cancer (BL-TNBC) affects at least 40,000 women in the United States.

PVT-006 is more likely to be effective in combination with existing anticancer agents, in basal-like triple-negative breast cancer subtype due to their mutations in DNA repair and replication pathways, which PVT-006 targets as its mechanism of action.

Preclinical safety studies will be conducted over the next 12 months to advance at least one of these candidates to an IND-stage to allow initiation of clinical studies in these highly unmet medical needs in women’s cancer.

We will also develop products regulated under Canada’s Natural Health Products Guidance and support claims with clinical based data as per current regulations.

Pre-clinical safety studies for pharmaceutical or NHP product development are ongoing to advance at least two of our product candidates.

Our Platform Technologies

BiPhasix Transdermal Drug Delivery Technology (Topical Platform)

Pivot has acquired worldwide rights from Altum for its patented topical transdermal drug delivery technology platform, or BiPhasix, which we will use for the delivery and commercialization of cannabinoid, cannabidiol (“CBD”) and tetrahydrocannabinol (“THC”) based products.

The BiPhasix technology has the potential to deliver drugs less invasively than by injections.

It also has the potential to topically deliver therapeutic amounts of drugs with better absorption rates, where creams, ointments or conventional liposomes have not been effective.

Dermal Barrier and Challenges

The skin is often the subject of intensive dermatological therapy.

However, except for certain low molecular weight compounds, it is seldom viewed as a route of delivery for systemically acting drugs.

This is due partly to the fact that, by design, the skin is a formidable barrier to penetration by external agents and the traditional arsenal of creams, ointments and gels have not proven themselves to be effective in delivery.

In order to reach their target site within the underlying layers of the skin or beyond the skin to the systemic circulation, topical drugs must first penetrate the stratum corneum, the outermost layer of the skin.

It is this layer which is considered to be the rate-limiting barrier to drug absorption.

For dermatological applications where the goal is to treat the skin, the residence time of drugs in the target tissue should be of sufficiently long duration since rapid systemic absorption may limit the therapeutic response and contribute to systemic side effects.

This latter case may be the fate of many small molecules formulated in conventional vehicles.

In some cases, it is desirable and possible to achieve systemic delivery of small molecules via the transdermal route (for example, nicotine).

However, larger molecules, whether intended for dermatological or systemic delivery, would normally not gain entry beyond the stratum corneum.

The goal is to have a safe delivery system that does not irritate or damage the skin barrier after repeated usage in patients.

Pivot will use BiPhasix as the next generation of patented liposomal delivery system where a number of features of liposomes are greatly improved.

In contrast to traditional liposomes that entrap a single, aqueous phase, our system is a complex system where the lipid bilayers entrap both aqueous and oil phases in the form of a stabilized emulsion.

BiPhasix is constructed with multi-compartmental lipid vesicles, each comprising of aqueous compartments and bi-layer compartments in addition to the following unique features of this patented delivery system:

Micellar compartments and oily compartments.

These additional features make it possible to achieve greater formulation versatility than previously attainable with traditional creams, gels, ointments or conventional liposomal delivery systems.

Thus, the BiPhasix delivery system combines the advantages of liposomes and micro-emulsions, offering a wider range of formulation options for a variety of drug substances:

Water soluble compounds;

Lipid soluble compounds;

Technical Facts of BiPhasix

BiPhasix is a dermal delivery system for macro-molecules and has the following characteristics:

Flexible and able to deliver both lipophilic and hydrophilic molecules;

Vesicles are composed of phospholipid bilayers (formed from pro-liposomal gel) which entraps an oil-in-water submicron emulsion;

Hydrophilic active pharmaceutical ingredients are incorporated into the aqueous phase of the oil-in-water emulsion, whereas lipophilic active pharmaceutical ingredients can be incorporated into the oil phase of the submicron emulsion.

Structure, assembly and properties of BiPhasix carrying an active pharmaceutical ingredient include:

Vesicles consist of concentric phospholipid bilayers;

Cationic submicron emulsion droplets;

Cationic surfactant micelles;

A water phase.

Additional facts regarding the BiPhasix delivery system include:

The amount of drug that can be incorporated include quantities at the microgram to milligram levels;

The size of molecules formulated are approximately 300 daltons (“Da”) to 100 kilodaltons (“kDa”);

Loading capacity range from 30-70%;

Increased stability of proteins are provided;

No organic solvents are used in the process;

No specialized manufacturing equipment are required;

BiPhasix products are easily scalable using standard pharmaceutical industrial equipment;

BiPhasix formulated product have been reviewed by the U.S.

Food and Drug Administration (“FDA”), the European Medicines Agency (“EMA”) and the The German Federal Institute for Drugs and Medical Devices (BfArM).

Delivery Mechanisms

The delivery of the BiPhasix vesicles is achieved by the uptake of the vesicles and encapsulated drug into the skin or mucosa via the lipid rich channels, followed by release of drug from the vesicles in a formulation-controlled manner.

The result may be either a rapid cutaneous transit time to produce primarily transdermal delivery of the drug, or depot formation within the skin with slow release for primarily dermal delivery of the drug.

The following is a hypothetical diagram showing penetration of the biphasic vesicles into the skin for drug delivery:

BiPhasix liposomes and transportation through the skin (in light blue)

Key Advantages of BiPhasix

The key advantages of BiPhasix are:

Alternative routes:

BiPhasix can serve as an alternative dosage form to injectables by providing less invasive routes of administration, such as dermal, transdermal, nasal, vaginal and rectal.

Controlled release:

BiPhasix can be formulated to effect varying degrees of tissue penetration and rate of release at the target site, in accordance with a desired clinical goals.

Bioavailability studies:

As shown in the tables below, BiPhasix can significantly enhance the bioavailability of many drugs, leading to improved clinical outcomes.

As shown in the above tables, BiPhasix has demonstrated excellent stability with most therapeutic agents tested, especially proteins, which are characteristically unstable in traditional vehicles.

Vulnerable drugs can be shielded from degradation in BiPhasix, thereby enhancing their clinical usefulness and commercial viability.

BiPhasix is compatible with most plastics and other container-closure systems.

Solvent-free and no animal product:

BiPhasix is formulated with biocompatible materials.

Neither organic solvents nor ingredients of animal origin are used in its manufacture.

Manufacturing feasibility:

Clinical supplies and commercial batches can be prepared using conventional manufacturing equipment and container closure systems.

Specialized equipment and extensive capital investment are not required.

Patented technology:

The BiPhasix patent pending technology provides market exclusivity for new NHP or prescription drug products containing Cannabinoids, CBD and THC.

Clinical experience:

As shown in the above tables, the BiPhasix delivery system has been tested in FDA and EMA approved trial settings delivering large molecule interferon alpha 2b to women to treat HPV induced cervical neoplasia.

Thrudermic Transdermal Nanotechnology (Topical Platform)

Pivot has acquired, in March 2018, the worldwide rights to Thrudermic’s patented Transdermal Nanotechnology for the development and commercialization of transdermal cannabinoids.

Developed in Israel, the Thrudermic lipid-based nano dispersion technology for topical cannabinoids uses FDA approved materials.

The technology has the ability to specifically formulate individual drugs to control and prolong drug release while maintaining steady therapeutic concentrations, The technology can handle water soluble and water insoluble drugs with no change to the skin morphology, no sensitivity to the digestive system, no pain from injections and no observed adverse reactions.

Solmic Solubilization Drug Delivery Technology (Oral Platform)

Pivot has acquired the worldwide rights to Solmic’s Solubilisation Technology for the development and commercialization of cannabinoid-containing natural extracts.

Solmic’s technology allows active ingredients to become water soluble without changing their composition and nature.

Solubilized substances that are packed in micelles are protected from degradation from light, stomach acid, and from enzymes released in the intestinal tract.

The micellisation process results in a stable, homogenous and transparent mixture, which significantly increases uptake of fat soluble ingredients from the gut into the blood system of fat soluble ingredients, resulting in greater bioavailability.

Ready-To-Infuse Cannabis Technology

Pivot’s patented Ready-To-Infuse-Cannabis (“RTIC”) process technology, acquired in February 2018, creates precise and repeatable dosing of cannabis by transforming concentrated cannabis oil into a stable, emulsifiable, odorless and flavorless powder form.

The derived powder may then be encapsulated and infused for use in beverages, edibles, lotions and additional health and personal care products.

The RTIC process is conducive for manufacturing of a wide array of products, including:

Capsules/Tablets:

One of our patents is issued for use in capsules and tablets.

Another of our patents has numerous claims for adding other active ingredients to tablets and capsules, such as Melatonin or Gingko Biloba, allowing for specific treatment for targeted effects.

Efficient mass production of capsules, conforming to GMP standards is part of our core competencies and manufacturing capabilities.

Production of capsules is scheduled for the third quarter of the calendar year 2018.

Beverage/Additive Stick Packs:

Single-serve stick packs are convenient and functional when used in hot beverages.

Stick packs are also highly functional.

Production of stick packs is scheduled for the third quarter of the calendar year 2018.

Pet Products:

Our patented cannabis powder will also be mass produced and packaged in bulk for both consumer pet health needs.

Production of pet powders is scheduled for the third quarter of calendar year 2018.

Lotions and Topical Creams:

Our patented lotion and topical technology will be mass produced and packaged for consumer health needs.

Production of lotions and topical creams is scheduled for the first quarter of calendar 2019.

Our Product Development Initiatives

Our product development initiatives will address unmet medical needs in metastatic endometrial, triple-negative breast and/or ovarian cancers.

Metastatic Endometrial Cancer

Endometrial cancer is the most common gynecological cancer in women and accounts for 6% of the cancers in women.

An estimated 43,470 cases of endometrial cancers were diagnosed in 2010 and 7950 deaths were associated with this cancer that year.

Endometrial carcinoma is divided into several histological categories based on cell type with endometrioid being the most common, which accounts for 75-80% of the cases.

Other aggressive pathological variants with a high risk of metastatic disease include papillary serous carcinoma (<10%), clear cell carcinoma (4%), squamous cell carcinoma (<1%), mixed (10%) and undifferentiated types.

Local and distal recurrences continue to remain a high risk for patients after they undergo surgery to remove the primary endometrial carcinoma.

Median time to recurrence is 2-3 years with 75-80% of the recurrence being extra-pelvic.

A small minority of patients with recurrent or advanced stage disease with solitary metastatic lesions may be amenable to radiation treatment with or without surgery.

Prognosis is poor for the remainder of women presenting with metastatic endometrial cancer with a median survival period of only 12 months.

The mainstay of treatment for metastatic endometrial carcinoma remains systemic hormonal therapy or cytotoxic chemotherapy.

Inactivating mutations of PTEN, a tumor suppressor gene, are found in 40-60% of endometrial cancers.

Loss of PTEN function results in constitutive activation of Akt which in turn upregulates mTOR activity resulting in cell proliferation.

Hormonal therapy is well tolerated in women with low-grade disease and those who are positive for estrogen receptor (ER+) and progesterone receptor (PR+).

Hormonal therapy includes agents such as progestins, which have an anti-estrogenic effect on the endometrium and produce marked changes in the glands and stroma.

Within the glandular epithelium of the endometrium, progesterone acts as an antagonist to the estrogen-mediated cell proliferation and also inhibits ER gene expression and increases degradation of ER.

Overall response rates following treatment with hormonal therapy using agents like medroxyprogesterone acetate or megestol acetate has been reported to be only 11-16% and progression-free survival (PFS) is only 4-6 months.

Low histologic grade coupled with expression of PR and an extended period between initial diagnosis and occurrence of metastatic disease have been shown to have better response rates to progestin therapy.

Response rates for PR+ endometrial cancer has been reported to be 37% compared to just 8% for PR-negative (PR-) endometrial carcinoma when treated with hormonal therapy.

Selective estrogen receptor modulators (SERMs) may also be used to treat low grade endometrial cancer.

Tamoxifen, which is used to both, prevent and treat breast cancer, has been shown to increase the incidence of endometrial cancer.

However, combination regimens with tamoxifen and progestins have been shown to have some benefit in low histologic grade endometrial carcinoma.

The use of aromatase inhibitors such as anastrazole and letrozole, for the treatment of advanced endometrial cancer in post-menopausal women, has shown poor response rates (<10%) with no correlation to the hormonal status.

The use of gonadotropin-releasing hormone (GnRH) agonists such as goserelin acetate also shown poor response rates and were deemed insufficient to treat metastatic endometrial cancer.

Cytotoxic chemotherapy is the mainstay for treatment of advanced metastatic endometrial cancer.

However, response rates are modest with progression-free survival (PFS) times of 4-6 months and overall survival of only approximately 12 months.

The most active classes of chemotherapy agents used for treating metastatic endometrial cancers are anthracyclines (doxorubicin, epirubicin), platinum compounds (cisplatin, carboplatin) and taxanes (paclitaxel, docetaxel) which produce response rates of approximately 20% as single agents.

Combination chemotherapy with multiple agents improves overall response rates to 33-57% depending on the combination.

Overall survival also improved slightly (approximately 15 months), but systemic gastrointestinal and myelotoxicity (Grade 3 and Grade 4) increased significantly in patients receiving such combination regimens.

Inhibitors of mTOR activity such as temsirolimus in combination with inhibitors of epidermal growth factor receptor (EGFR) and anti-angiogenic agents suppressing vascular endothelial growth factor (VEGF) are being evaluated for the treatment of metastatic endometrial cancer.

Since novel Pivot compounds such as PVT-005 show “synthetic lethality” with chemotherapy agents such as cisplatin in tumors that have loss of tumor suppressor function in p53 or PTEN, such combinations would provide novel chemotherapy options for the treatment of metastatic endometrial cancers.

Triple-Negative Breast Cancers

Triple-negative breast cancers (TNBC) are defined as tumors that lack the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2.

Approximately 12-17% of women with breast cancer have TNBC, representing approximately 170,000 breast cancer patients.

These patients have a relatively poor outcome and cannot be treated with endocrine therapies or agents targeted to epidermal growth factor receptor type 2 (HER2).

A close cousin of TNBC is basal-like breast cancer (BLBC) which is characterized by absence or low level expression of ER and absence of HER2 expression.

Many tumors may meet the definition of both TNBC and BLBC.

Both TNBC and BLBC occur more commonly in young women, particularly Black and Hispanic women, when compared to women from other racial and ethnic backgrounds.

Approximately 75% of women with TNBC or BLBC have a mutation in BRCA1, a breast cancer susceptibility gene.

Because TNBC is a heterogenous disease, many pathological and immunohistochemical sub-classification systems have been proposed to provide greater homogeneity within TNBC subtypes.

Recently five molecular subtypes have been proposed for TNBC to allow improved clinical development strategies to stratify TNBC patients.

These include:

1) basal-like TNBC characterized predominantly by mutations in DNA damage repair deficiency and some growth factor pathway expression:

2) mesenchymal-like TNBC (ML-TNBC) with epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) features;

3) immune-associated TNBC (I-TNBC);

4) luminal/apocrine TNBC (LA-TNBC) with androgen receptor (AR) overexpression;

and 5) HER2-enriched TNBC (HER2e-TNBC).

The predominant grouping of TNBC is basal-like (BL-TNBC) which constitutes between 25-80% of all TNBC.

Within the basal-like subtype, there are two subgroups and basal-like 1 (BL1-TNBC) is enriched in cell cycle related genes and DNA-damage repair pathways.

Nearly 25% of breast cancers harbor a mutation in DNA repair, mainly in homologous recombination (HR) when double-stranded (DS) breakage occurs – which appears similar to the genetic deficiencies of BRCA1 or BRCA2 mutation carriers.

Alterations in DNA-damage response or repair mechanisms usually lead to genomic (microsatellite) instability and carcinogenesis.

In addition to DNA-damage response deficiencies, 85% of BL-TNBC patients have mutations in p53 which results in a loss of tumor suppression.

Since TNBC are aggressive tumors, chemotherapy regimens include targeting DNA repair complex (like platinum agents and taxanes), p53 (like taxanes), cell proliferation (like anthracyclines) and targeted therapy.

BL-TNBC appears to have good response rates to chemotherapy regimens containing platinum agents (such as cisplatin and carboplatin).

In addition to administration in the adjuvant setting (after surgery), several studies have evaluated the combination chemotherapeutic regimens in neoadjuvant setting.

For instance, cisplatin as a single agent in the neoadjuvant setting gives a pathological response rate of nearly 22%;

which improves to 28% when cisplatin is administered in combination with paclitaxel;

and further improves to 65% when a triple combination of cisplatin:paclitaxel;epirubicin is administered to TNBC patients in the neoadjuvant setting.

However, response rates in metastatic TNBC are lower for single- or double agent chemotherapy in TNBC, and it remains a high unmet medical need.

Given the molecular subtype of BL-TNBC, using agents that target DNA-damage repair deficiencies appears to be a good strategy to combine novel drugs with platinum containing regimens to improve response rates.

For instance, combination of platinum drugs with novel agents targeting poly-ADP ribose polymerase (PARP), have been evaluated in TNBC patients.

Chemotherapy regimens combining novel pyrrolobenzodiazepine dimers (PBDs) from Pivot (PVT-006) with cisplatin or carboplatin to target BL-TNBC will offer novel therapeutic regimens to improve response rates and progression-free survival (PFS) in metastatic BL-TNBC patients.

Metastatic Ovarian Cancer

Ovarian cancer is the most lethal gynecological cancers and is the fifth leading cause of deaths in women in the United States.

It is usually diagnosed at a late stage and has a 5-year survival rate of approximately 30%.

The majority of ovarian cancers are diagnosed after they have spread into the peritoneal cavity and the major cause of ovarian cancer-associated mortality is believed to be due to therapy-resistant metastatic disease.

It is estimated that 21,290 new cases of ovarian cancer were diagnosed in 2015 and 14,180 ovarian cancer patients died that year.

Current treatment strategies for advanced ovarian cancer consist of aggressive surgery (referred to as cytoreduction or tumor debulking).

In order to clear the tumor from the pelvis, the surgery often involves en bloc resection of the ovarian tumor, reproductive organs and the sigmoid colon, and primary bowel reanastamoses.

The surgical goal is to remove as much tumor burden as possible, since cytoreduction has been associated with improved survival.

Post-operatively, most ovarian cancer patients will receive chemotherapy with platinum- (usually carboplatin) and taxane- (usually paclitaxel) containing regimens.

While these agents are administered intravenously, there is some evidence that administration of these regimens through the intraperitoneal route improves overall survival benefit in such patients.

The World Health Organization (WHO) has categorized ovarian cancers into four subtypes based on their histology:

1) serous-papillary ovarian carcinoma which resembles the papillary architecture of the fallopian tubes;

2) endometrioid carcinoma which is often associated with endometriosis and resembles endometrioid carcinoma of the uterus;

3) mucinous carcinoma resemble either the endocervical glands or gastrointestinal epithelium;

and 4) clear cell carcinoma of the ovary which is a rare subtype and shares morphological features of both, serous and endometrioid carcinomas.

In the last few years, there have been some more genetic insights into various ovarian cancers and two molecular subtypes of ovarian cancers have been identified.

Type 1 ovarian cancers affect younger patients and are comprised of low-grade serous-papillary and endometrioid carcinomas and have low grade resistance to carboplatin-taxol chemotherapy regimen, but have indolent disease and tend to have a median survival of 82 months.

Type 2 ovarian cancer is most prevalent in post-menopausal women, and it is initially very sensitive to platinum-containing chemotherapy regimens, but median survival is only 30 months.

Type 1 serous-papillary ovarian tumors typically have mutations in BRAF, KRAS, ERBB2 and have microsatellite (genomic) instability.

Type 1 endometrioid, mucinous and clear cell ovarian cancers have similar mutations to the serous-papillary ovarian carcinoma and in addition have additional mutations in b -catenin and PTEN.

The most frequent (50-80%) mutations in high-grade (Type 2) serous ovarian cancers involve the tumor suppressor gene, p53.

Other important genetic changes in high-grade serous tumors include changes in BRCA1 and BRCA2 and amplification of AKT2 serine/threonine kinase and PI3K mutations.

The biological behavior of ovarian carcinomas and its confinement to the peritoneal cavity provides us with an opportunity to develop novel chemotherapeutic combination regimens using novel Pivot pyrrolobenzodiazepine dimers (PBDs) in combination with carboplatin and paclitaxel, especially via the intraperitoneal route to minimize systemic toxicity.

Furthermore, due to the genetic similarity of abdominal ovarian cancers, it provides us an opportunity to shrink all types of metastatic ovarian tumors with such novel combination regimens.

Clinical Trial Phases

The following section describes the most common phases of clinical drug trials with reference to the clinical trial requirements that we anticipate will be required for each of our planned products.

Our product development initiatives will address unmet medical needs in health care.

MARKET SIZE (1)

Solmic Solubilisate / Oral

Cancer supportive care (CINV) (chemo-induced nausea and vomiting)

Solmic Solubilisate / Oral

Restless leg syndrome

Solmic Solubilisate / Oral

Pain and inflammation (for opioid withdrawal)

Solmic Solubilisate / Oral

Cancer supportive care (mucositis relief)

BiPhasix / Topical

Female sexual dysfunction (HSDD) (hypoactive sexual desire disorder)

BiPhasix / Topical

Pain and inflammation (joints/opioid withdrawal)

BiPhasix / Topical

Dermatology (skin irritation/redness/ itching)

BiPhasix / Topical

Eye disease (glaucoma, intra-ocular pressure)

Thrudermic / Topical

Pain and inflammation (opioid withdrawal)

Solmic Solubilisate / Oral

Migraine (nausea, vomiting, dizziness, sensitivity to light, sounds and smells)

(1) Derived from IMS data

Clinical Trial Phases (for Pharmaceuticals Products Only)

The following section describes the most common phases of clinical drug trials with reference to the clinical trial requirements that we anticipate will be required for each of our pharmaceutical products in the future and funding permitting.

Pre-Clinical Trials

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Completion of these trials is subject to our ability to obtain adequate financing.

We anticipate initiating and completing at least one Phase II trial of either PVT-005 or PVT-006 at a cost of approximately $8.4 million over a 12 month period.

It is our goal to begin our trial six months after the completion of the required financing;

however, we will not establish a firm start date until we raise sufficient financing, which there is no guarantee that we will be able to do.

We will not establish a firm start date until we raise sufficient financing, which there is no guarantee that we will be able to do.

The trial protocol for our Phase II trial has been developed with input from our clinical advisors.

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Studies in this phase are categorized by some companies as “Phase IIIB studies”.

While not required in all cases, it is typically expected that at least two successful Phase III trials will be necessary to demonstrate a drug’s safety and efficacy in order to obtain approval from appropriate regulatory agencies, such as the FDA in the United States, the Therapeutic Goods Administration in Australia or the European Medicines Agency in the European Union, for example.

While not required in all cases, it is typically expected that at least two successful Phase III trials will be necessary to demonstrate a drug’s safety and efficacy to obtain approval from appropriate regulatory agencies, such as the FDA in the United States, the Therapeutic Goods Administration in Australia or the European Medicines Agency in the European Union, for example.

Once a drug has proved satisfactory after Phase III trials, the trial results are usually combined into a large document containing a comprehensive description of the methods and results of human and animal studies, manufacturing procedures, formulation details and shelf life.

This collection of information makes up the regulatory submission that is provided for review to the appropriate regulatory authorities in different countries.

They review each submission, and, it is hoped, give sponsors approval to market the particular drug.

They review each submission, and, it is hoped, give sponsors approval to market the drug.

Most drugs undergoing Phase III clinical trials can be marketed under FDA norms with proper recommendations and guidelines, but the drugs must be recalled immediately from the market if any adverse effects are reported.

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Our ability to pursue any Phase IV trials which may be required of us or which we may undertake voluntarily will be subject to our ability to adequately finance those trials and to successfully complete Phase III trials.

Markets for Our Planned Products

Estimated Sales

Metastatic Endometrial Cancer (PVT-005)

Triple-negative breast cancer (PVT-006)

Sales are conservatively estimated for US only, using the estimates of incidence and prevalence of the oncology indication, and assuming modest pricing and market penetration.

Research and Development

We have not spent any amount on research and development expenses for the last two fiscal years.

From our inception on June 10, 2002 to January 31, 2017 we spent $282,715 on research and development activities.

We anticipate that we will incur approximately $8.4 million in research and development expenses over the next 12 months;

however this may change if we are unsuccessful in obtaining sufficient additional financing.

Intellectual Property

We own the common law trademark rights in our corporate name and logo as well as the trademark for “INDUS PHARMACEUTICALS”.

With the exception of the trademark for IndUS, we have not registered any of our trademark rights for protection.

We have also secured exclusive worldwide licensing rights and title in and to the following patents through our acquisition of IndUS Pharmaceuticals: