CNBX PHARMACEUTICALS INC. Company Overview
The Company is a biopharmaceutical corporation specializing in the discovery,
development and commercialization of novel effective cannabinoid-based products
and innovative technologies for the treatment of cancer.
Our core technology is a continuously evolving bioinformatics platform that utilizes high-throughput screening technology, advanced data analytics, and proprietary methodologies to rapidly examine the physiologic effect of multiple cannabinoid compounds on tumor cells. This technology enables us to screen thousands of cannabinoid combinations weekly, generating multiple datasets on the anti-tumor properties of different cannabinoid formulations and ratios. We conduct a broad range of preclinical research on cannabinoids through our bioinformatics platform, which informs the development of our product candidates.
Our lead product candidate is RCC-33, an oral capsule for the treatment of colorectal cancer ("CRC"). RCC-33 contains high concentrations of the cannabinoids CBDV and CBGA, which have demonstrated complex synergistic anti-tumor activity in our in vitro studies, with minimal psychoactive effects. We are currently in the early planning stage of a clinical development pathway for RCC-33. We plan to conduct further preclinical studies to establish the safety and efficacy of RCC-33 in an in vivo murine model of colorectal cancer. Subject to the results of our preclinical studies, we intend to proceed to phase 1/2a clinical study in the second half of 2022.
Cannabics SR is a lipid-based capsule containing a standardized formulation of
cannabinoids that we are developing as a product candidate for the treatment of
cancer anorexia-cachexia syndrome ("CACS"). With a rapid onset of action and
sustained effects for up to 6-8 hours, we believe that the convenience of once
or twice daily oral dosing of Cannabics SR may improve quality of life and
increase patient compliance with treatment regimens, leading to better health
outcomes. A two-year pilot study of Cannabics SR led by Dr.
Another product candidate we are developing is Cannabics CDx, a drug sensitivity
test designed to provide innovative decision support to healthcare providers
interested in personalizing cannabinoid-based cancer therapies. Cannabics CDx
applies data analytics and high-content drug sensitivity screening integrated
with our proprietary database to measure the effectiveness of cannabinoid
compounds on a patient's biopsy, suggest preferred alternatives, and alert
healthcare providers to cannabinoids that may be contraindicated. We believe
that Cannabics CDx will meet a significant unmet need of the growing population
of cancer patients being treated with cannabis by enabling healthcare providers
to more precisely tailor cannabinoid treatments to a patient's cancer and
clinical profile. We are currently seeking strategic partners for a clinical
validation study expected to commence in 2022 to assess the sensitivity and
specificity of Cannabics CDx with a view towards commercializing Cannabics CDx
in
11 Cancer and Cannabinoids
Cancer is a general term used to describe a group of more than 100 related
diseases characterized by uncontrolled growth and spread of abnormal cells,
leading to the development of a mass commonly known as a tumor, followed by
invasion of the surrounding tissues and subsequent spread, or metastasis, to
other parts of the body. Despite enormous investment in research and the
introduction of new treatments, cancer remains a critical area of unmet medical
need. According to the
Over the past decade, there has been growing interest in the therapeutic value of cannabinoid compounds in oncology. Cannabis has long been suggested as a well-tolerated, safe, and effective option to help patients cope with cancer related symptoms by reducing nausea and vomiting, alleviating cancer pain, stimulating appetite, and improving quality of life. Beyond their palliative benefits, however, cannabinoids have also been receiving increased attention for their anti-cancer potential, which we believe may one day revolutionize cancer therapy.
Cannabinoids are a diverse class of chemical compounds that occur naturally within cannabis plants and are pharmacologically similar to cannabinoids produced by the human body, known as endocannabinoids. Endocannabinoids form part of the human endocannabinoid system (ECS), a complex biological network that also includes cannabinoid receptors and enzymes involved in cannabinoid formation, transport, and degradation. The ECS is regarded as an important endogenous system implicated in regulation of the most vital biological processes to maintain homeostasis, assisting the body to remain stable and balanced despite external, or environmental, fluctuations (Source: Current Pharmaceutical Design, 2016;22(12):1756-1766).
Cannabinoids have demonstrated selective anti-tumor properties in preclinical studies, exerting anti-proliferative, proapoptotic, anti-angiogenic, and anti-metastatic and anti-inflammatory effects depending on tumor type and specific setting (Source: Cancer Medicine, 2018:7(3):765-775). These effects appear to be more pronounced when cannabinoids are used together versus being administered separately, a mechanism known as the entourage effect. We believe, therefore, that cannabinoid combinations may hold promise for an improved anti-proliferative strategy for cancer management.
In addition to their potential role as anti-cancer agents, cannabinoids have been observed to act synergistically with some conventional antineoplastic drugs, such as chemotherapeutic agents, enhancing their effectiveness (Source: Cancer Medicine, 2018;7(3)765-775). This raises the potential for combinational therapies that may increase the range of chemotherapeutic options available to patients and enable targeting of tumor progression at different levels while also permitting dosages of cytotoxic drugs to be dramatically reduced without compromising efficacy.
Figure 1: Synergistic effects of cannabis extracts and chemotherapies on cancer biopsy after treatment with the same extract and three different chemotherapy combinations
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As of the date of this filing, we are not aware of any cannabinoid-based therapies approved for the treatment of cancer.
Our Proprietary Bioinformatics Platform
We have developed a continuously evolving preclinical bioinformatics platform that enables us to evaluate and classify the physiological impact of multiple cannabinoid compounds on various cancer cells. Utilizing state-of-the-art high-throughput screening and flow cytometry, our platform is capable of testing thousands of compounds weekly, allowing us to rapidly and effectively examine their interactions with a growing library of human cancer cell lines and biopsies. Through the large body of data generated by our platform, we are accumulating in-depth knowledge of the various therapeutic effects of cannabinoids and patterns of cannabinoid ratios that demonstrate meaningful physiologic impact on cancer.
Our bioinformatics platform includes the following:
Ø high-throughput screening, high content screening, flow cytometry, machine
learning, robotics, and proprietary methodologies;
Ø a library of human cancer cell lines and thousands of different combinations
and ratios of cannabinoid compounds in a costumed matrix;
Ø a growing database of biological response data;
Ø in-house extraction, processing methodologies, and analytical techniques
that yield well-characterized and standardized extracts;
Ø collaborations with regulated cannabis producers that may expand our
cannabinoid compound library and provide us with access for future
proprietary cultivars;
Ø fully integrated in-house research and development; and
Ø regulatory expertise.
Once a series of potentially active cannabinoids is identified for a specific cancer type, we then test and confirm their activity through in vitro and ex-vivoevaluation studies to determine their potential activity. Through this process, we are able to assess their therapeutic potential. The results of our pre-clinical experiments provide starting points for our clinical development programs.
Biopharmaceutical Collaboration
As medical cannabis becomes increasingly recognized for its therapeutic potential in the age of personalized medicine and genomics, we believe that there is a growing global demand by biopharmaceutical companies for research and diagnostic tools that both facilitate and accelerate the generation of biological information for the development of cannabinoid drugs and formulations. We believe that our bioinformatics platform will be of benefit to such companies and may therefore represent collaborative opportunities, market potential and downstream value-creation for the Company.
Finding novel ways to treat and cure diseases is a fundamental challenge in
biomedical research. Unsuccessful clinical trials are the most expensive
obstacle for drug development because of the immense costs and the low success
rate. Only 1 out of 10 drugs successfully pass through clinical development,
with 80% of drugs excluded before Phase 3 clinical trials (Source:
We believe that our bioinformatics platform could make the development of cannabinoid-based drugs more successful by providing a more accurate and reliable drug target prediction method. Our proprietary analytics may benefit biopharmaceutical companies across a range of applications, including patient selection and recruitment for clinical trials and identification of new targets for drug development.
13 Development Pipeline
We are currently developing a portfolio of proprietary technologies and formulations with a variety of research, analytic, and therapeutic applications. Our most advanced development programs include the following:
Current
Development
Product Candidate Indication/Description Status Expected Next Steps Partner(s)
RCC-33 Colorectal Cancer Pre-clinical Pre-IND meeting with FDA in None
the second half of 2021.
Phase 1/2a clinical trial
expected to commence in the
second half of 2022
Cannabics SR Cancer Phase 0 Additional pilot studies None
Anorexia-Cachexia expected to commence in the
Syndrome second half of 2021
Cannabics CDx Drug sensitivity test Pre-clinical Clinical validation study to To be
for cannabinoid-based commence in 2022 determined
cancer therapies.
We continue to conduct research and seek collaborations for new advances in biotechnology that may lead to the development of additional product candidates.
RCC-33 for Colorectal Cancer
Overview
Our lead product candidate is RCC-33, which we are developing as a treatment for CRC. RCC-33 is an oral capsule containing a proprietary formulation of cannabinoids that have demonstrated synergistic efficacy in reducing the viability of human colon cancer cell lines in preclinical studies.
Colorectal Cancer
CRC is one of the more common forms of cancer worldwide, representing a
significant challenge to the global healthcare system. According to the
Most CRCs begin as a noncancerous growth called a polyp that develops on the
inner lining of the colon or rectum. The most common kind of polyp is called an
adenomatous polyp or adenoma. According to the
14
CRC usually develops slowly, over a period of 10 to 20 years. The complex
sequence of events occurring during initiation, development and propagation of
adenocarcinomas is likely the result of a lifelong accumulation of mutations
caused by both genetic and environmental factors known as the adenoma to
carcinoma sequence. While the specific cause of any particular case of CRC is
often unknown, more than one-half of all cases and deaths are attributable to
lifestyle and environmental factors, such as smoking, unhealthy diet, high
alcohol consumption, physical inactivity, and excess body weight (Source:
CRC does not usually cause symptoms until the disease is advanced, therefore
early detection of adenomas by screening is vital. If not treated or removed, an
adenoma can become a potentially life-threatening cancer. Treatment options for
CRC patients depend on several factors, including the type and stage of cancer,
possible side effects, and the patient's preferences and overall health.
Surgical removal of the tumor is the most common form of treatment, particularly
in the early stages of malignancy. Patients with more advanced stages of CRC may
be given adjuvant chemotherapy to kill any cancer cells remaining after surgery,
though standard chemotherapy is associated with severe side effects and provides
marginal benefit to the majority of patients. While radiation therapy is often
used to treat rectal cancer, it is not generally recommended for colon cancer
patients except in the later stages of the disease (Source:
Cannabinoids and Colorectal Cancer
A new emerging area of scientific understanding in the treatment of CRC lies in
the development and use of cannabinoid therapeutics. The ECS is regarded as an
important regulatory system in the gastrointestinal tract, being involved in
several important functions such as motility, secretion, sensation,
inflammation, and carcinogenesis. Recent studies advocate that the ECS plays a
critical role in the development of CRC and should therefore be considered as an
appropriate target for CRC inhibition (Source: Frontiers in Pharmacology,
2016;7:361). The expression of ECS components in CRC has been found to be
increased and associated with poorer prognosis and advanced stages of disease
(Source:
Research on the effects of cannabinoid compounds on CRC has demonstrated an ability to reduce the viability of CRC cell lines in vitro (Source: Cancer Medicine, 2018;7(3):765-775), while there is also convincing scientific evidence that cannabinoids are able to prevent or reduce carcinogenesis in different animal models of colon cancer (Source: Expert Review of Gastroenterology & Hepatology, 11:10, 871-873).
We believe that cannabinoids are a promising therapeutic agent for the treatment of CRC. We have conducted several in vitro unpublished studies using our bioinformatics platform and can confirm absolutely that cannabinoids cause necrosis in colon cancer cells. While many cannabinoids demonstrate levels of toxicity on cancer cells, we have found that certain cannabinoid extracts and combinations show increased levels of toxicity relative to other isolated or combined cannabinoids. These findings have spurred the development of RCC-33, our product candidate for the treatment of CRC.
Figure 2: Synergistic effects of different cannabinoid combinations on viability of a colon cancer cell line.
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15
RCC-33
We are developing RCC-33 as an oral capsule containing high concentrations of the cannabinoids CBDV and CBGA in a novel formulation, which we believe may be effective in the treatment of adenocarcinomas of the colon. The cannabinoids in RCC-33 have demonstrated complex synergistic anti-tumor effects in combination, with no psychoactive effect. In our preclinical in vitro studies evaluating the influence of 15 different cannabinoids on human colon cancer cell lines (RKO, HCT116), alone and in combination, RCC-33 demonstrated clear efficacy in reducing the viability of colon cancer cells versus alternative cannabinoid combinations.
Development Plan
We are currently in the early planning stage of a clinical development pathway for RCC-33. We plan to conduct further preclinical studies to establish the safety and efficacy of RCC-33 before proceeding with first-in-human clinical testing. LAST PR RE FDA PRE-IND STUDIES - TALK ABOUT SCALPA
Preclinical Studies
We have now written and shall shortly begin a proof of concept non-clinical study in a murine model for colon adenocarcinoma to validate the results obtained in our cell-based assays. In addition, we plan to conduct non-clinical safety studies following Good Laboratory Practice (GLP) to evaluate the systemic and local toxicity of escalating doses of RCC-33 and establish dosing parameters. The results of these preclinical studies, which are expected in the fourth quarter of 2020, will guide our planned Phase 1/2a clinical trial. The non-clinical requirements to support the development program will be verified with the FDA at a pre-IND meeting expected to take place in the second half of 2021. Such studies may include repeated dose toxicity studies, male and female fertility studies, embryofetal development studies, animal abuse related studies, pharmacokinetics studies, drug-drug interaction studies, and others.
Clinical Trials
We plan to evaluate the safety, tolerability, and pharmacokinetic properties of
RCC-33 in a Phase 1/2A ascending dose clinical trial in CRC patients, commencing
in the second half of 2022. The clinical trial will examine the tolerability,
pharmacokinetics, pharmacodynamics, and efficacy of multiple doses of RCC-33 in
CRC patients. We are currently identifying potential contract research
organizations and clinical trial centers to conduct the Phase 1/2a human proof
of concept study, which is estimated to cost
Subject to the results from our Phase 1 trials, we plan to submit an IND to the FDA for RCC-33 with the clinical protocol for a Phase 2 double-blind placebo controlled clinical trial evaluating RCC-33 in patients with CRC at various dosing levels versus placebo. The outcomes from the planned Phase 2 human proof of concept trial will inform our decision regarding further steps in the clinical development of RCC-33.
At this time, we do not expect to independently develop RCC-33 up to regulatory
approval. Instead, we plan to seek a pharmaceutical partner or partners to
continue our commercialization efforts. However, we may also seek to further
advance the RCC-33 program with additional human clinical trials prior to
finding a suitable pharmaceutical partner or partners. We estimate that it will
take more than five years to bring RCC-33 to market, if at all, at a cost of
more than
16
Cannabics SR for Cancer Anorexia-Cachexia Syndrome
Overview
At the same time, we are pursuing our work on colorectal cancer, we are
continuing our development of Cannabics SR as a product candidate for the
treatment of CACS. Cannabics SR is a sustained-release oral capsule containing a
standardized compound of cannabinoids that has demonstrated a clinically
significant weight increase in CACS patients in a peer-reviewed pilot study
conducted by Dr.
Cancer Anorexia-Cachexia Syndrome
CACS is a common complication of cancer associated with high morbidity and mortality. It is a complex metabolic syndrome in which a persistently elevated basal metabolic rate is not compensated for by adequate calorie or protein intake, causing involuntary and progressive weight loss leading to increasing functional impairment in cancer patients, especially in advanced stages of the disease. Once established, CACS cannot presently be reversed using available pharmacological or nutritional support techniques.
Unlike starvation, body-weight loss in CACS patients arises mainly from loss of muscle mass, characterized by increased catabolism of skeletal muscle and decreased protein synthesis. This weight loss is associated with important clinical outcomes such as increased morbidity, diminished effectiveness of chemotherapy, muscle wasting, inflammation, fatigue, and reduced survival expectations. The impact of CACS on the patient is not, however, limited to the effect of weight loss. Quality of life, functional abilities, symptoms, psychological outcomes, and social aspects are all affected by CACS.
According to the
The cause and subsequent development of CACS is still poorly understood, but several factors and biological pathways are known to be involved, including inflammation, decreased secretion of anabolic hormones, and altered metabolic response. While there have been important advances in the study of CACS over the past decade, including progress in understanding its mechanisms and the development of promising pharmacologic and supportive care interventions, there is presently no effective pharmacologic therapy for CACS.
Cannabinoid Therapies for CACS
Cannabis has long been suggested as a well-tolerated, safe, and effective option
to help patients cope with cancer related symptoms with fewer serious side
effects than most prescription drugs currently used as anti-emetics, analgesics,
and the like. As such, cannabinoids are finding application in palliative care
for reducing nausea and vomiting, alleviating cancer pain, and stimulating
appetite, as well as improving quality of life in cancer patients. Dronabinol
(Marinol®) and nabilone (Cesamet®), two drugs based on synthetic cannabinoids,
have each been approved by the FDA for the treatment of chemotherapy-related
nausea in patients who do not respond to conventional antiemetic therapy.
Another drug, nabiximols (Sativex®), a specific cannabis extract, is approved in
17 Cannabics SR
Cannabics SR is an oral composition in the form of a hydroxypropylmethylcellulose (HPMC) capsule containing a patent-pending formulation of cannabinoid extracts suspended in a lipid emulsion. It provides a relatively rapid onset of action, typically within 30-40 minutes, followed by a gradual and sustained release of active cannabinoids, resulting in a steady state level of beneficial effects for up to 6 to 8 hours with each capsule. Cannabics SR provides a consistent, predictable concentration of cannabinoids with an absorption profile and bioavailability of active ingredients that we believe to be superior to other oral cannabinoid administrations. We believe that the multifactorial benefits of the active pharmaceutical ingredients in Cannabics SR address an unmet medical need for a safe and effective treatment of CACS, leading to improved patient adherence and better health outcomes.
Clinical Development
In 2016, we commenced a two-year pilot study to evaluate the influence of
Cannabics SR capsules on CACS, and, in particular, on weight loss in advanced
cancer patients. The study was led by Professor
Patients were administered 2 × 10 mg of Cannabics SR per 24 hours for six months. Participants were weighed at each physician visit. The primary objective of the study was a weight gain of ?10% from baseline. Despite various limitations, the preliminary study demonstrated a weight increase of 17.6% of patients with doses of 5 mg × 1 or 5 mg × 2 capsules daily, without significant side effects. The remaining patients had stable weights. Also, all patients who remained in the study for at least 4.5 months reported an increase in appetite, as did 83% of the patients who completed the study. For 50% of the patients who completed the study, there were reports of pain reduction and sleep improvement. Additional results showed a significant decrease of appetite loss complaints among 83% of the patients who completed the study. (See Bar-Sela, Gil et al. "The Effects of Dosage-Controlled Cannabis Capsules on Cancer-Related Cachexia and Anorexia Syndrome in Advanced Cancer Patients: Pilot Study." Integrative Cancer Therapies vol. 18 (2019): 1534735419881498. doi:10.1177/1534735419881498.)
We intend to conduct additional pilot studies in
Commercialization
The results of our planned pilot studies may permit us to commercialize
Cannabics SR in
Cannabinoids and Personalized Medicine
While preclinical research during the last decade has stimulated interest in the therapeutic potential of cannabinoid compounds in oncology, one of the challenges facing healthcare providers and patients in selecting a cannabinoid based therapy has been the diversity of the cannabis plant, which encompasses thousands of distinct profiles, each with its own chemical composition and effects. After decades of highly restrictive regulation, there is presently a lack of clinically relevant information as to which cannabinoids are best suited to the unique medical needs of a patient across multiple lines of therapy. The result has left healthcare providers and patients at a loss as to which cannabinoids may be best suited to treat the unique cancer profiles of individual patients.
18 Cannabics CDx
We believe that the success of personalized medicine depends on the development of accurate and reliable diagnostics. Our goal is to expand the scope of personalized medicine across the cancer care continuum to include cannabinoid-based therapies and enable clinicians to make better informed decisions leading to improved clinical outcomes and lower healthcare costs. To that end, we are developing Cannabics CDx as a product candidate to provide clinical decision support data to healthcare providers interested in personalizing cannabinoid-based cancer therapies. We believe that by making cannabinoid therapy selection more accurate and accessible, Cannabics CDx may play a significant role in ushering medical cannabinoids into the mainstream of oncology.
Cannabics CDx is an innovative drug screening system that measures the effectiveness of cannabinoid compounds on a patient's biopsy, identifies alternatives, and alerts healthcare providers to cannabinoids that may be contraindicated. Biopsied samples are delivered by courier to our laboratory, where we perform novel cannabinoid sensitivity tests on them using our high-content drug sensitivity screening integrated with our bioinformatics platform. We then apply advanced analytics to the test results and other relevant biological and clinical information provided by each patient's healthcare provider to derive clinical support data from which healthcare providers can make better informed treatment decisions.
Figure 4:Sample personalized patient report produced by Cannabics CDx
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By enabling healthcare providers to more precisely tailor cannabinoid therapies to a patient's cancer and clinical profile, we believe that Cannabics CDx will meet a significant unmet need of the growing population of cancer patients being treated with cannabis.
19 Validation
We are currently planning a clinical validation study expected to commence in 2022 to assess the sensitivity and specificity of Cannabics CDx. We are currently seeking strategic partners to collaborate on the validation and commercialization process.
Intellectual Property
Our success depends in significant part on our ability to protect the proprietary nature of our Product Prospects, technology and know-how, to operate without infringing on the proprietary rights of others; and to defend challenges and oppositions from others and prevent others from infringing on our proprietary rights, including our provisional patents described below.
We plan to continue to seek patent protection in
Results of Operations
For the Three Months Ended
Revenues
We have not received royalties during the three months ended
Operating Expenses
For the three months ended
We incurred a financial income of
Net loss
Net loss decreased by
20
Liquidity and Capital Resources
Overview
As of
Liquidity and Capital Resources during the Three Months Ended
We used cash in operations of
We had cash flow from investing activities of
We will have to raise funds to pay for our expenses. We may have to borrow money from shareholders, issue equity or enter into a strategic arrangement with a third party. There can be no assurance that additional capital will be available to us. We currently have no arrangements or understandings with any person to obtain funds through bank loans, lines of credit or any other sources. Since we have no such arrangements or plans currently in effect, our inability to raise funds for our operations will have a severe negative impact on our ability to remain a viable company.
Going Concern
Due to the uncertainty of our ability to meet our current operating and capital
expenses, our independent auditors included an explanatory paragraph in their
report on the audited financial statements for the year ended
Our unaudited financial statements have been prepared on a going concern basis, which assumes the realization of assets and settlement of liabilities in the normal course of business. Our ability to continue as a going concern is dependent upon our ability to generate profitable operations in the future and/or to obtain the necessary financing to meet our obligations and repay our liabilities arising from normal business operations when they become due. The outcome of these matters cannot be predicted with any certainty at this time and raise substantial doubt that we will be able to continue as a going concern. Our unaudited financial statements do not include any adjustments to the amount and classification of assets and liabilities that may be necessary should we be unable to continue as a going concern.
There is no assurance that our operations will be profitable. Our continued existence and plans for future growth depend on our ability to obtain the additional capital necessary to operate either through the generation of revenue or the issuance of additional debt or equity.
Off-Balance Sheet Arrangements
We currently have no off-balance sheet arrangements that have or are reasonably likely to have a current or future material effect on our financial condition, changes in financial condition, revenues or expenses, results of operations, liquidity, capital expenditures or capital resources.
21 Critical Accounting Policies
The preparation of financial statements in conformity with accounting principles
generally accepted in
See Item 7, "Management's Discussion and Analysis of Financial Condition and
Results of Operations" and Note 2, "Summary of Significant Accounting Policies"
in our audited consolidated financial statements for the year ended
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