CNBX PHARMACEUTICALS INC. Our Business:
We are a pre-clinical-stage, platform technology biopharmaceutical company which has developed proprietary innovative medicines in areas of significant unmet medical needs in oncology, with a current focus on colorectal cancer ("CRC"). Our drug candidate under development for colon cancer is RCC-33, a first-in-class therapy being developed primarily in two settings: one to reduce tumor cell activity in colon cancer patients as a standalone in neoadjuvant treatment or "window of opportunity" at the time after colonoscopy, prior to cancer staging; and another for patients with refractory to therapy and adjuvant to surgery also at the time after colonoscopy. The Company hopes to start first in human Phase I/II clinical trials in 2023. Neoadjuvant treatment is the administration of a therapy before the surgical treatment to improve patient outcome, and our business strategy is to advance our programs through clinical studies including with partners, and to opportunistically add programs in areas of high unmet medical needs through acquisition, collaboration, or internal development.
The company is currently preparing to launch Phase I/II (a) clinical study in
2023, for the evaluation of its lead drug candidates Cannabics SR for the
treatment of patients with advanced cancer and cancer anorexia cachexia syndrome
(CACS) and RCC-33 for the treatment of colorectal cancer. The company's
activities are centered around the company's biological laboratory facilities
located in
Our company's core activities consist of:
· Drug Discovery: development of novel molecular formulations and drug
candidates;
· Intellectual Property: filing of corresponding IP to protect our products;
and
· Regulatory Affairs: initiation of the regulatory pathway for each drug
candidate in our development pipeline
Our current business model is to undertake an FDA regulatory pathway for each of the new drug candidates under IND (Investigational New Drug) classification and complete a successful Phase I/II(a) clinical study (toxicity and proof of concept in humans). In reaching this milestone, where an initial feasibility in humans was demonstrated, the company will have gained several commercial opportunities for capitalizing on each such product candidate, including entering into commercial agreements with larger pharma corporations. Accordingly, our company does not engage in any manufacturing, distribution, or sales of products, nor is it foreseeable to expect that we will in the near future.
2. Development pipeline:
2.1. Cannabics SR for Cancer Anorexia-Cachexia Syndrome
Overview
We are developing 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.
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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.
Current treatments for CACS are generally based on nutritional support and CACS pathophysiology-modulating drugs, with the most common being the progestogens, megestrol and medroxyprogesterone, and corticosteroids. Progestogens appear to stimulate appetite and improvements in body weight by increasing adipose tissue, but have not been confirmed to augment lean body mass. Megestrol also carries an increased risk of mortality and thromboembolism. Nonetheless, megestrol is the only FDA approved treatment option for CACS and no drug to date has been shown to be superior to it in efficacy and tolerability. Corticosteroids are also considered effective in stimulating appetite and reducing fatigue but should only be used for short periods and in selected cases because of side effects from longer term use, such as insulin resistance, fluid retention, steroidal myopathy, skin fragility, adrenal insufficiency, and sleep and cognitive disorders. Other drugs are being investigated or are in development. Given the dearth of approved therapies, we believe that CACS remains a significant area of unmet medical need.
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
Despite interest in cannabinoid-based therapies as a treatment for CACS, their use has been limited by impediments beyond the legal status of cannabis. The most significant obstacle is the lack of clinical research demonstrating their efficacy. While there is evidence that cannabinoids improve appetite, body weight, body fat level, caloric intake, mood, and quality of life in cancer patients, the few studies on these effects have yielded mixed and inconclusive findings. In addition, some of these studies have suffered from methodological constraints that limit any ability to draw firm conclusions.
The therapeutic use of cannabinoids has also been inhibited by limitations associated with traditional administration routes that reduce their effectiveness. Smoking and ingestion of cannabis suffer from wide variability in potency due to a lack of standardized and reproducible formulations. The ingestion of unformulated cannabis has also been associated with poor absorption and low bioavailability versus other administration routes, requiring higher doses and a greater risk of negative side effects. Additionally, the lack of available information on cannabinoid strains has made it difficult for healthcare providers to establish dosing rates. In our experience, however, the principal concern of patients with respect to medical cannabis lies in the undesirable side effects, such as disorientation and dizziness, which result from significant variability in peak blood levels of active cannabinoids soon after administration. We further believe that these side effects, which are common among immediate release methods, are a significant factor in the failure of patients to adhere to recommended treatment regimens and are therefore a pervasive threat to their health and wellbeing.
12 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.
Cannabics SR capsules contain only food grade materials without any artificial additives. The active ingredients of each capsule are standardized in composition, formulation, and dose, and are comprised of only pure, natural extracts of active cannabinoids from selected strains of medical cannabis. All excipients are recognized by the FDA as Generally Regarded as Safe.
In addition to the therapeutic potential of Cannabics SR as a treatment for CACS, we believe that our SR technology may be formulated to serve the unique needs of patients suffering from other indications for which a sustained release of a cannabinoid formulation may be beneficial.
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. During the study, after some patients reported several psychoactive side
effects, the dosage of each capsule was reduced to 5 mg. Almost no side effects
were reported with the 5 mg dosage. Participants were weighed at each physician
visit. The primary objective of the study was a weight gain of ?10% from
baseline. Of 24 patients
Despite various limitations, the preliminary study demonstrated a weight
increase of ?10% in 3 out of 17 (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
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Figure 1: Appetite loss among the six patients
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Commercialization
The results of our planned pilot studies may permit us to commercialize
Cannabics SR in
On
Cancer and Cancer Anorexia Cachexia Syndrome (CACS) Market Analysis
The dynamics of the cancer cachexia market are expected to shift in the coming years as a result of the positive outcomes of some of the rare candidates during the development stage by key players that are in the early stages of clinical development have the potential to create a significant positive shift. The emerging therapies are projected to be launched during the forecast period. In addition, the dearth of effective therapies for this condition presents a great opportunity for pharma companies to create novel drugs because there is less competition in the cancer cachexia market. Moreover, the rising awareness about the condition is also impacting the growth of the cancer cachexia market positively.
The Global Cancer Cachexia Market Size is projected to reach
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https://www.fortunebusinessinsights.com/cancer-cachexia-market-103262
2.2 RCC-33: colorectal cancer treatment drug candidate:
Our anti-neoplastic flagship product under development, RCC-33, is an antitumor
drug candidate for the treatment of colorectal cancer, which is the 3rd most
diagnosed and 2ndmost lethal of all cancers, with approximately 2M new cases
being diagnosed annually worldwide and a current market estimated at
The RCC-33 proprietary formula consists of a specific synthetic cannabinoid molecular composition that has demonstrated the potential to reduce colorectal cancer tumor volume by over 30% in repeated in-vivo studies performed.
Overview 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).
Dysregulation of the ECS owing to variation in the expression and function of
cannabinoid receptors or enzymes or the concentration of endocannabinoids has
been associated with several diseases, including cancer (Source:
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Cannabinoids can interact with the cannabinoid receptors in the ECS, sometimes with a higher affinity than endocannabinoids. As a consequence, all the processes regulated by endocannabinoids are susceptible to interference by cannabinoids. The ability to use cannabinoids to modulate the ECS encompasses several attractive pharmacotherapeutic targets for systemic anti-cancer treatment and has sparked considerable research examining cannabinoid action on cancer cells (Source: Pharmacological Reviews, 2006;58(3):389-462).
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 2: 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 anti-cancer treatment.
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
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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.
Current Standard of Care
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:
CRC is a heterogeneous disease with distinct clinical, molecular, and
pathophysiological characteristics. As a result, the response to treatment is
variable between patients, even when they are diagnosed at the same clinical
stage. Such heterogeneity remains an obstacle to the optimization of treatment
for each individual. Researchers are continuing to investigate new treatment
options, such as immunotherapy and targeted therapy, that focus upon the genes,
proteins, and other factors in a particular tumor (Source:
Immunotherapy uses the body's own immune system to kill cancer cells. There are already several FDA-approved immunotherapy options for CRC, such as pembrolizumab (Keytruda®), nivolumab (Opdivo®), and ipilimumab (Yervoy®). Many immunotherapies that have shown promise in addressing other types of cancer are also being tested for CRC. While immunotherapy has had some encouraging results, significant limitations remain. Its efficacy is often unpredictable, and the treatment can lead to the body becoming resistant or result in off-target toxicities where the body's immune system attacks healthy tissue. Immunotherapy may take longer than other protocols and it is substantially more expensive than classical treatments (Source: Pharmacy & Therapeutics, 2017;42(8):514-521).
Targeted therapy uses drugs to target specific molecules inside cancer cells or
on their surface to slow the growth of cancer, destroy cancer cells, and relieve
cancer symptoms. There are different types of targeted therapy drugs, each
working differently depending on what molecule the drug is targeting. A
treatment is chosen based on the types of molecules expressed on the patient's
tumor cells, which allows doctors to tailor cancer treatment for each person.
Several targeted therapy drugs, such as bevacizumab (Avasin®) and cetuximab
(Erbitux®), are already used to treat advanced CRC. Despite showing clinical
promise, targeted therapy has challenges, such as tumor heterogeneity,
off-target toxicity, and acquired resistance (Source:
We believe that there is no "magic bullet" to cure cancer and that a personalized combination of cancer treatments may be the best course for long term survival benefits in each case. To that end, the development of more prevention strategies and novel agents will be essential.
Cannabinoids and Colorectal Cancer
One area of increasing interest 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:
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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 to confirm 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 3: Synergistic effects of different cannabinoid combinations on viability of a colon cancer cell line.
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RCC-33
We are developing RCC-33 as an oral capsule or solution 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. Importantly, we could detect significant reduction effect on tumor development in mice inoculated with human colorectal cancer cells.
[[Image Removed]] 18 Development Plan
The company is currently preparing to launch Phase I/II (a) clinical study in 2023, for the evaluation of its lead drug candidates Cannabics SR for the treatment of patients with advanced cancer and cancer anorexia cachexia syndrome (CACS) and RCC-33 for the treatment of colorectal cancer. We plan to conduct further preclinical studies to establish the safety and efficacy before proceeding with first-in-human clinical testing.
Preclinical Studies
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 2023, will guide our planned Phase I/II(a) clinical trial. The non-clinical requirements to support the development program will be verified with the FDA at a pre-IND meeting. 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
Cannabis SR and RCC-33 in a Phase I/II(a) ascending dose clinical trial in CRC
patients, commencing in the first quarter 2023. 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 I/II(a)
human proof of concept study, which is estimated to cost
Subject to the results from our Phase I trials, we plan to submit an IND to the FDA for RCC-33 with the clinical protocol for a Phase II 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 II human proof of concept trial will inform our decision regarding further steps in the clinical development of RCC-33.
Our Pipeline:
In addition to RCC-33, our colorectal cancer treatment drug candidate, the company has several other drug candidates under development, including PLP-33 for the local treatment of Lateral Spreading, or Sessile, colorectal polyps during colonoscopy, BRST-33 for the treatment of breast cancer, MLN-33for the treatment of Melanoma and PRST-33 for the treatment of prostate cancer. These additional drug candidates are in the early stage of development and the company expects to complete the in-vivo research for each product by end of 2023. (see Fig. 4).
19 Fig. 4 [[Image Removed]]
2.3 Product lines currently not actively developed:
The company has several product lines that are currently not being actively developed following company's decision to focus its resources and attention exclusively on the development of its FDA route drug candidates, and SR Capsule described above. The product lines not actively developed include:
Cannabics CDx (evaluate) Drug Sensitivity Test
Cannabics CDx is an ex-vivo drug sensitivity test under development to provide healthcare providers with clinical decision support data from which they can identify, for a particular cancer patient undergoing cannabinoid therapy, which cannabinoids or cannabinoid combinations may have the most beneficial anti-cancer effects, and which cannabinoids may be contraindicated.
Company may revisit this decision at a later stage after launching the first in human clinical studies for the validation of its colorectal cancer treatment drug candidate RCC-33.
20 3. Market opportunity for cancer treatment drug candidates: 3.1. Neoadjuvant therapy:
According to the
[[Image Removed]] Limitations: · Mild to severe side effects · Suppressed immune system · Potential resistance of tumor residues to postoperative chemotherapy *
* "nCRT increases ITGH and may result in the expansion of resistant tumor cell populations in residual tumors".
Frontiers in Oncology. 2019
The Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer-The
Impact in Intratumoral Heterogeneity.
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3.1.1 Neoadjuvant therapy in rectal cancer
Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemoradiotherapy than high rectal cancer.
[[Image Removed]] [[Image Removed]] 3.1.2 Neoadjuvant therapy in breast cancer
In early breast cancer, surgery is the mainstay of curative treatment. Complementary local radiotherapy and systemic - adjuvant endocrine therapy or chemotherapy treatments are associated with the aim of reducing the risk of relapse according to the clinicopathological characteristics of the tumor. However, the possibility of administering these therapies prior to surgery in neoadjuvant setting offers several advantages:
· reduction in tumor size to improve respectability, · increased rate of conservative surgery improving esthetic results, · reduction in the extent of axillary surgery, · early treatment of micrometastatic disease 22
Fig5. Asco Guidelines for neoadjuvant therapy in breast cancer
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According to ASCO guidelines most of the patients are eligible for neoadjuvant chemotherapy and are the end consumers of BRST-33, while the current treatment regimen negates severe side effects.
Side effects and risks of standard of care:
· nausea or vomiting · hair loss · nail or skin changes · appetite loss · weight changes · diarrhea or constipation · mouth sores · fatigue 23
3.2. Cannabinoid Neoadjuvant Therapy
For some time now, the FDA has promoted clinical studies on Cannabinoids as a growing range of stakeholders has expressed interest in development of drugs that contain cannabis and compounds found in cannabis. Recent legislative changes have also opened new opportunities for medical cannabis clinical research. As this body of research progresses and grows, the FDA is working to support drug development in this emerging scientific arena.
RCC-33 & BRST-33 - Potential safe drugs improving rectal and breast cancer neoadjuvant standard of care
RCC-33 & BRST-33 anticipated advantage over standard of care:
· Non-Suppressed immune system
· potential low toxicity which is even more important in neoadjuvant
treatment since patients will suffer less side effects. Since the two
drug candidates are based on two natural molecules (cannabinoids) found
in the Cannabis plant, the safety of the molecules in the short and long
run is potentially lower. Not like in a new drug entity in which
toxicity could not be predicted.
· Overcoming Potential resistance of tumor residues to postoperative
chemotherapy
3.3. Cancer Immunotherapy:
Our business strategy is to advance our programs through clinical studies with
partners, and to opportunistically add programs in areas of high unmet medical
needs through acquisition, collaboration, or internal development. Despite
significant advances in oncology, there is still a large unmet need in treating
patients with solid tumors, especially those with advanced disease
Patients undergoing most of currently existing treatments benefit a reduction in tumor size but often relapse and develop more aggressive disease. The residual population of chemotherapy-resistant tumor cells is enriched by Tumor Initiating Cells (TIC) previously known as cancer stem cells (CSC). The TaGeza technology is targeting TIC/ CSC by re- purposing small molecules and generating specific antibody generation for targeted immunotherapy ADC (Antibody drug conjugates).
CSCs were first found in colorectal cancer. Because of its heterogeneity, drug resistance etc., it was difficult to completely eliminate CSCs using traditional treatment methods. The remaining CSCs can cause tumor recurrence and invasion, and ultimately the death of the patient. Therefore, developing a therapy that can effectively target CSCs will greatly promote the treatment of GI cancers (Sun, Y., Li, B., Cao, Q. et al. Targeting cancer stem cells with polymer nanoparticles for gastrointestinal cancer treatment. Stem Cell Res Ther 13, 489 (2022). https://doi.org/10.1186/s13287-022-03180-9)
Antibody Drug Conjugates ADC
Antibody-drug conjugate (ADC) is a new emerging class of highly potent
pharmaceutical drugs, which is a great combination of chemotherapy and
immunotherapy. Antibody-drug conjugate (ADC) is typically composed of a
monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a
chemical linker. It combines both the advantages of highly specific targeting
ability and highly potent killing effect to achieve accurate and efficient
elimination of cancer cells, which has become one of the hotspots for the
research and development of anticancer drugs. Since the first ADC, Mylotarg®
(gemtuzumab ozogamicin), was approved in 2000 by the
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Global sales of currently marketed ADCs are forecast to exceed
4. Outsourced GMP manufacturing and commercial operation:
4.1. Outsourced GMP manufacturing
Our current position is that all of our Chemistry Manufacturing and Controls (CMC) required for the approval process of our drug candidates is to be outsourced. The RCC-33 formulation, as well as all additional drug candidates in our pipeline, while inspired by natural molecules, could consist only of formulations made from chemically synthesized molecules, or APIs (Active Pharmaceutical Ingredients). Our Company is not engaged in the development of any botanical or botanically based product/s. Additionally, in view of our upcoming submission of a pre-IND meeting request with the FDA, the Company the company will need to enter into an agreement with a manufacturer and supplier of GMP (Good Manufacturing Practice) grade APIs suited for Clinical Stage Products. There are a couple of large and long-established US corporation with a long track record of working with the FDA. Accordingly, the manufacturer will also need to provide support to CNBX throughout an IND filing process, including providing all necessary and related information concerning CMC in the form of a comprehensive technical package to be presented to the FDA. APIs supplied under said agreement will be used by Company in Phase I/II (a) clinical studies that it is planning to launch in 2023.
4.2. Commercial Operations
We have not established a sales, marketing, or product distribution infrastructure. We plan to commercialize any drugs we develop through licensing arrangements and strategic partnerships with established companies in the pharmaceutical industry having strong marketing capabilities and distribution networks. We generally intend to advance our drug candidates through Phase I and Phase II clinical trials as appropriate in order to establish their clinical and commercial potential before negotiating the terms of any licensing or collaboration. We believe that this approach will achieve the fullest marketing and distribution potential of any drugs or other products that we may develop in the short term.
5. Core activities: 5.1. Drug Discovery
Conduct all screening and pre-clinical research at in-house state of the art laboratory facilities
Our Research and Development:
To address these problems and improve clinical outcomes,
We aim to treat a wide scope of cancers both as the main treatment and as a
conjugate to conventional chemotherapy. We believe a significant need remains
for novel drugs for patients
Our government licensed laboratory operates a unique, custom designed and built research and development laboratory which combines high throughput screening, (HTS) capabilities with the most advanced data tools allowing us to enable miniaturization and automation of a variety of biological assays. The automated system is comprised of:
1. High Content Screening (HCS) Platform, which is an automated cellular
imaging and analysis platform designed for quantitative microscopy.
2. Flow Cytometry, which enables multi-parametric single cell analysis.
3. Automated workstation, for liquid handling for dispensing accurate and
reproducible volumes of liquids and compounds.
4. Multimode microplate reader, designed for fast measurements of numerous
biological reactions/processes.
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The integration of these instruments is enabled via a robotic arm, which allows a continuous process which utilizes all instruments.
Readouts generated from these instruments provide us with insights to the effect of our cannabinoid library on parameters such as, proliferation inhibition, apoptosis induction, angiogenesis prevention and toxicity on cancerous cells.
These experiments will produce multiplexed data composed of images of cells, cell specific markers and the extent/signal of the biological response. The biological response will be measured using different concentration of cannabinoids and their combinations, thus determining the most effective cannabinoid treatment for a specific cancer type.
In vitro Studies - Drug Screening
We have a proprietary procedure of high throughput screening (HTS) and high content screening (HCS) for the detection of correlations between cannabinoid ratios, dosages and anti-tumor activity using a growing library of human cancer cell lines and creating an enlarged variety of Cannabis-based compounds. We examine the biological activity of these compounds on tumor cell lines of distinct tissue lineage and creating a highly valuable therapeutic data. We Screen for the most potent cannabinoid/natural extracts. Our goal in the invitro studies is to build a library of both shaulfied and natural cannabinoid extracts and to reveal their biological impact on a library of cancer cell lines. The HTS technology enables us to gain this data base in a faster manner and to reveal more mechanisms of action that are related to the genetics of the cancer. We are now in the process of merging our data with sophisticated data mining to help find meaningful insights of both treatment and outcome.
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, 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 drug candidates.
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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-vivo evaluation 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.
5.2. Intellectual Property
Expand and protect the technology, inventions, and trade secrets that are critical for business development.
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
Scientific Advisory Board :
The development of our drug candidates is taking place with the close guidance
and support of our clinical advisory team consisting of world-renowned experts,
including doctors and scientists with specific expertise in the fields of cancer
research, cancer treatment, Oncology, Hematology, Melanoma, Gastroenterology, AI
and FDA regulation. Our team of experts is highly qualified and respected
worldwide, some members having numerous publications in their respected names,
including in high authority peer reviewed publications such as
27 Prof.Caroline Robert (MD)
Prof.
Prof.Amos Toren (MD)
Prof.
Prof.Zamir Halpern (MD)
Prof.Noam Shomron (Ph.D.)
Professor
Dr.Sigal Tavor (MD)
Dr.Yonina Tova (MD)
Dr.
28 Dr.Erez Scapa (MD)
Dr.Ilan Hochman , VP R&D
Dr. Lior Eshdat, VP IP
Dr. Eshdat holds a Ph.D. in organic chemistry and brings over 14 years of
experience in intellectual property practice. Before he became an Israeli Patent
Attorney Dr. Eshdat held a post-doctoral research fellowship at the
Dr.Dana Ben-Ami Shor (MD)
Dr.
Dr.
A Senior Advisor in the field of Regulation, Validation and Quality. Dr.
Prof.
29 Results of Operations
For the Three Months Ended
Operating Expenses
For the three months ended
We incurred a financial loss of
Net loss
Net loss decreased by
Liquidity and Capital Resources
Overview
As of
Liquidity and Capital Resources during the Three Months Ended
We used cash in operations of
We had no cash flow from investing activities during the three months ended
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
30
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.
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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