Mediforum - MF-018

A new class of pain relief compounds designed to combat the opioid crisis

Targeting pain with a non-opioid solution

 
❶A different approach to pain relief for chemotherapy patients
Just about every chemotherapy (platinum, taxane, vinca alkaloid, etc.) treatment causes peripheral neuropathic pain, as most of them target cell division which produces collateral damage in the destruction of healthy structures, in particular the peripheral nervous system. No chemotherapy treatment without severe side-effects exists thus far and a substantial percentage of patients cease treatment due to the severe pain encountered.

 
❷Naturally derived compounds for pain relief
Japan's Tsumura & Co. is currently administering a cinnamom bark/aconite root decoction called Goshajinkigan to patients (research is in the early clinical study stage). There is a lack of related studies in Korea, however, our joint development team has published 12 SCI papers on naturally derived drug compounds researched over the past decade. We have completed a patent application and the publication of a SCI paper that investigates the mechanism and effects of Cinnamomum cassia bark extract.

 
❸Immense market demand and need to fulfill
Opioid pain medication and anti-inflammatory painkillers form an addressable market of $18 billion each in the global pain-relief drug market. The market is predicted to grow to over $40 billion by 2023. In addition to the immense size of the market, there is a tremendous societal impact on the use and misuse of opioids. We aim to address that with a completely non-addictive drug to combat the destructive effect of opioid misuse.

Constructed animal model of chemotherapy-induced neuropathic pain

 
* TWL, thermal withdrawal latency
 

Confirmed pain reduction effect of Cinnamomum cassia bark extract

 
Preclinical Animal Studies
Results of tail withdrawal latency showing the tolerance to pain by the mice.

 
❖ Study Results
After administering Cinnamomum cassia bark extract to an animal that had been injected with chemotherapy regimens, the response time to pain increased when compared to the negative and positive control groups. ✤Pain-reduction effect of Cinnamomum cassia bark extract for pain induced by chemotherapy was confirmed.
WECC - Water Extracts of Cinnamomum Cassia, an MF018 compound
 

Active mechanism of Cinnamomum cassia bark extract confirmed

 
❶Inhibition of activation of astrocytes in spinal cord
 

 
Glial fibrillary Acidic Protein (GFAP) is a monomeric intermediate filament protein found in astrocytes and not found outside of the central nervous system. This protein is not routinely secreted in blood and is only released after cell death or injury. These characteristics suggest GFAP presence may be an ideal marker for nerve injuries and associated chronic pain. The graph shows the number of GFAP positive cells after the administration of Oxaliplatin (Eloxatin), a chemotheraphy drug with a common side-effect of neuropathy from neurotoxicity. ✤The subjects that were administered WECC based MF-018 had statistically reduced levels of GFAP positive cells compared to the subjects that were administered phosphate buffered saline (PBS) placebo.
 

 
❷Inhibition of activation of microglia in spinal cord
 

 
Ionized calcium binding adapter molecule 1 (IBA1), also known as allograft inflammatory factor 1, is a protein that is specifically expressed in activated macrophages and microglia. IBA1 is found in tissues with inflammation and has a positive correlation with cancer development, rheumatoid arthritis, kidney disease and diabetes. IBA1 may be an accurate indicator of the presence of these conditions. The graph shows the number of IBA1 positive cells after the administration of Oxaliplatin (Eloxatin), a chemotheraphy drug with a common side-effect of neuropathy from neurotoxicity. ✤The subjects that were administered WECC based MF-018 had statistically reduced levels of IBA1 positive cells compared to the subjects that were administered phosphate buffered saline (PBS) placebo.
 

 
❸Inhibition of pro-inflammatory cytokines in spinal cord
 

 
Interleukin 1 beta (IL1β) is a cytokine protein in humans encoded by the IL1B gene. Tumor necrosis factor (TNF)is also a cytokine protein, used by the immune system for signaling between cells. Increased levels of either protein expresses inflammation in the body and elevated levels can cause carcinogenesis. The graph shows the concentration of IL1β and TNF after the administration of Oxaliplatin (Eloxatin), a chemotheraphy drug with a common side-effect of neuropathy from neurotoxicity. ✤The subjects that were administered WECC based MF-018 had statistically reduced levels of IL1β and TNF compared to the subjects that were administered phosphate buffered saline (PBS) placebo.
 

MF-018 Clinical Trials

 
Phase 2 MF-018 clinical trials as an Investigational New Drug was approved by the Ministry of Food and Drug Safety in 2019
 