The Need

Many chronic inflammatory diseases, such as autoimmune disorders, asthma, and arthritis, lack effective treatments that can provide long-term relief without significant side effects. Current medications often focus on symptom management rather than addressing the underlying causes of inflammation, leading to a need for more targeted and sustainable solutions. Patients with these conditions face a daily struggle to manage their symptoms, often requiring complex medication regimens that may not fully control their disease or that come with severe side effects. Additionally, the economic burden of these diseases is substantial, both for individuals and healthcare systems, highlighting the urgent need for innovative treatments.

The Solution

Raphael Pharmaceutical offers a promising solution to these challenges by harnessing the anti-inflammatory properties of cannabis. Through extensive research and collaboration with Rambam Hospital's Medical Cannabis Research Center, the company has revealed the mechanism of activity of cannabinoids, and developed a deep understanding of how cannabinoids interact with the body's immune system to reduce inflammation. By leveraging this knowledge, Raphael Pharmaceutical aims to develop targeted medicines that disrupt the intercellular communication pathways involved in chronic inflammation and autoimmune diseases. These innovative treatments have the potential to offer patients more effective and sustainable relief, improving their quality of life and reducing the economic burden of chronic inflammatory diseases on individuals and healthcare systems.

The Technology

Cannabinoids Backgrounder

• The cannabis plant has a variety of strains and contains multiple naturally occurring compounds referred to as cannabinoids .
• More than 100 cannabinoids have been identified, including the two main cannabinoids:
  • psychoactive delta-9-tetrahydrocannabinol (“THC”)
  • non-psychoactive cannabidiol (“CBD”)
• Cannabinoids have demonstrated clear health benefits, and the FDA has approved several drugs that contain natural or synthetic cannabinoids, such as Epidiolex®, Marinol®, Syndros®, and Cesamet®.
• The natural, extracted oil formulations in Raphael Pharmaceutical’s product candidates are derived from unique CBD strains with low levels of THC (less than 0.3% THC) and enhanced anti-inflammatory activity.

Differentiated Cannabinoid Technology Platform

Raphael Pharma is Developing a Novel, Patentable Formulation Designed to Treat Inflammation

• Cannabinoids are the active pharmaceutical ingredients (“API”)
• Our formulated oil contains a mix of non-psychoactive, purified, isolated cannabinoids derived from a specific novelty exclusive Strain named (CBX) High CBD and extremely low-THC

Cannabis

Raphael Pharma is Developing a Novel, Patentable Formulation Designed to Treat Inflammation

• • Cannabinoids are the active pharmaceutical ingredients (“API”)
  • Our formulated oil contains a mix of non-psychoactive, purified, isolated cannabinoids derived from specific strains of low-THC cannabis

Uniqueness of Our Technology Platform

• • Leverages in depth scientifically-based understanding of the mechanisms of cannabinoids activity
  • Ability to decode how cannabinoids impact the network of intercellular communications during inflammation
  • Proprietary real time-polymerase chain reaction method has identified 12 different receptors to cannabinoids in both human and mice models 
  • The API in our formulation is designed to interact and communicate with the endocannabinoid system in the human body, activating cannabinoid receptors expressed by immune cells
  • Knowledge of which cannabinoid receptors participate in downregulation of inflammation in cells
  • We believe our platform technology can be applied to various chronic conditions linked to inflammation.

Existing Therapies for RA

• • DMARDs – disease modified antirheumatic drugs; the most prevalent conventional DMARDs are methotrexate, sulfasalazine, hydroxychloroquine, and leflunomide
  • Biologic DMARDs – made using molecular biology and consisting of proteins; target specific molecules, cells and pathways that cause inflammation and damage tissue; examples include tumor necrosis factor (TNF) inhibitors, Interleukin-1 inhibitors, Interleukin-6 inhibitors, T-cell inhibitors, and B-cell inhibitors
  • Corticosteroids – commonly referred to as steroids, corticosteroids are a type of anti-inflammatory drug

Current Treatment Options May Not Be Suitable for Everyone

Encouraging Pre-Clinical In-Vitro Study for RA Product Candidate

• • Employed immune cells derived from human donors , capable of differentiating into macrophages or T cells and to secreting cytokines 
  • Screened cannabis-derived oil extracts to determine influence on cytokine secretion
  • Identified a non-psychoactive cannabis strain, referred to as “CBX”, which demonstrated favorable effects:

Highly Purified Cannabinoid (HPC1) as Treatment Option for Patients with Rheumatoid Arthritis

• Our preclinical experiments revealed a highly purified cannabinoid (HPC1) that effectively reduces inflammation in a mice model of rheumatoid arthritis
• The cannabinoid reduced the expression levels of IL1b, TNF alpha and IL6 in the joints and peripheral blood of the sick mice
• This study suggests that HPC1 has the potential to slow the progression of RA by acting as an anti-inflammatory agent.

Proof of Concept Clinical Study Commenced

• In March 2024, engaged Citruslabs, a contract research organization (“CRO”)
• In May 2024, commenced proof of concept clinical study in the United States
• This study aims to evaluate the efficacy of purified cannabinoid (HPC1) in patients with active RA
• Enrolled the first of 12 patients in May 2024
• If successful, we anticipate commencing Phase II in 1H 2025 and commercialization as soon as 2026

Robust Pipeline Based on Platform Technology

Our Research has Demonstrated the Potential of Cannabinoid-Based Treatment for Lung Inflammation

• Human and Mouse Model Study - using cells derived from human donors and a mouse model for systemic inflammation and severe lung inflammation, we have found that a specific high-CBD strain (CBX) is effective in preventing cytokine storms (reduces the secretion of IL6 and TNF alpha as well as the inflammation in the mice lungs); also inhibits the migration of immune cells to the lungs 
• Our findings were published in Frontiers in Immunology  in May 2022
• We are developing a novel molecule-based formula as a treatment for patients with autoimmune disease and chronic lung inflammation. The combination of molecules A and B exhibits a synergistic effect, leading to a reduction in cytokine secretion in the lungs of a mouse model for lung inflammation:

Progression of Current R&D pipeline (U.S.)

• • RA – lead product candidate; in-human proof of concept underway
  • Autoimmune Diseases / Lung Inflammation – mouse model study complete; pre-clinical commenced
  • Oncology – for cancer treatment effects like cachexia, fatigue, anemia, pain and depression (palliative)
  • Other – to be determined

Media Coverage