Treatment for Alzheimer's Dementia
memory enhancement and concentration aid

Theraputic treatment for dementia without the negative side-effects

What is dementia?
What is dementia?
Dementia is a set of symptoms related to brain function that shows as impairment in memory, linguistics abilities, temporal and spatial understanding, judgment and abstract thinking abilities which negatively impact one's ability to function and carry out everyday activities. It results in a tremendous strain in the daily life of the one afflicted and is detrimental to their relations with friends, family and caregivers around them. Alzheimer's is the most common cause of dementia, accounting for 60-70% of the cases of dementia worldwide.
Types of Dementia
Types of dementia and their distribution
Source: Ministry of Health and Welfare, 2012
Severity of Dementia
Cognitive disorder and behavioral disorder
(linguistic ability, visuospatial ability, task execution, calculating numbers, emotion and personality, short-term / long-term memory loss)
Source: Ministry of Health and Welfare, 2012
Severity of Dementia
Dementia patients by age groups (from 65 years old or older)
Source: National Institute of Dementia, 2017
Causes of dementia and drug treatments
1. Accumulation of beta-amyloid proteins in the brain that clump together
2. Inflammatory response to tau proteins, oxidation damage, vascular tissues, etc.
3. Other forms of nerve damage
Product Name Drug Compound Usage/Dosage Active Mechanism Side-Effects
Razadyne tablet (4, 8mg) Razadyne PR SR capsule (8, 16, 24mg) Galantamine 2 times/day for 4 weeks, 4 mg/dosage; 2 times/day after 4 weeks, 8 mg/dosage (maximum dosage of 24mg/day) Acetylcholinesterase (AChE) inhibitor Nausea, vomiting, diarrhea, stomachache, indigestion, loss of appetite, fatigue, dizziness, headache, drowsiness, weight loss
Exelon capsule (1.5, 3, 4.5, 6mg) Rivastigmine 2 times/day, 1.5mg/dosage; Titration up to 3, 6, 9, 12mg/day in 2-week intervals (maximum dosage of 12mg/day) Acetylcholinesterase (AChE) inhibitor Nausea, vomiting, diarrhea, stomachache, loss of appetite, dizziness, agitation
Aricept tablet (5, 10, 23mg) Donepezil 5mg/dosage once a day (for over 4 weeks); maintain a 5-10mg dosage per day Acetylcholinesterase (AChE) inhibitor Nausea, vomiting, muscle cramps, fatigue, vertigo, diarrhea
Namenda tablet (10mg) Namenda oral drops (10mg/g) Memantine 10mg/day; gradually increase dosage by 10mg/day in 1 week intervals; spread dosages of 20-30mg evenly over the course of the day (maximum dosage 60mg/day) NDMA receptor antagonist Dizziness, confusion, sleep disorder, agitation, fatigue, headache, constipation
Source: Seoul National University, Bundang Hospital, Phamacology Department, 2005
PM-012 Clinical Trials
Phase 3 PM-012 clinical trials as an Investigational New Drug was approved by the Ministry of Food and Drug Safety in 2018
PM-012 Clinical Trial Approval
PM-012 clinical trials in progress
Project Milestones & Timeline
Project Code: PM012 - (650mg/tablet of seven extracts that include rehmannia root)
Type of Drug: Natural product, Tablet (coated), Oral administration
Indication: Dementia (Alzheimer's disease)
Target: Clinical trials (local and global)
PM-012 Clinical Trials institution status and respective locations
PM-012 Clinical Trial Locations In Seoul
11 locations across Seoul
4 locations across Gyeonggi-do and Incheon
PM-012 Clinical Trial Locations In Korea
10 locations across other non-metropolital areas
PM-012 Pharmacological Effects
PM-012 pharmacological effects from in vivo testing (1)
Confirmation of pharmacological effects of PM-012 in mouse model of Alzheimer's type dementia.

Test substance: PM-012
Control Group Active Comparator Group Test Group
Saline solution Donepezil 0.6mg/kg PM-012 100mg/kg, PM-012 400mg/kg
12 weeks 12 weeks 12 weeks
❖ Study results
When administering PM-012 to mice with Alzheimer's disease:
1. an increase in glucose metabolism (adsorption) was shown
2. neurogenesis activity of neurons was exhibited
✦ Results from 18F-FDG micro-PET scanner
Joint research with Korea Atomic Energy Research Institute
In mice administered with PM-012, they exhibited a 67% increase in the rate of glucose metabolism in the brain and a 62% increase in the hippocampus.
PM-012 PET Imaging Brain Glucose Metabolism
PM-012 pharmacological effects from in vivo testing (2)
The human brain produces new neurons even at an advanced age
PM-012 Brain Neurogenesis
Confirmed the growth of new neurons (dyed red) in the brain tissue of a 68 year old individual
Source: LlorensLab
* Related Papers
1. Nature Medicine, Volume 25, pg554-560 (2019)
2. Nature, Volume 567, pg433 (2019)
The hippocampus:
1. has the role of transmitting signals to other regions of the brain
2. is responsible for learning and memory
3. controls emotional behavior and certain movements
4. regulates the function of the hypothalamus
Anatomical Location of the Hippocampus
Anatomical Location of the Hippocampus
Dissected View of the Hippocampus
Cross Sectional View of the Hippocampus
PM-012 promotes new neurogenesis in the CA1 and DG regions of the hippocampus
PM-012 PET Imaging Neurogenesis in CA1 DG Regions of Hippocampus
The potential of PM-012 as a treatment for dementia
* Related papers: Mol Neurobiol (2016) 53:5401-5412
PM-012 PET Imaging Neurogenesis in CA1 CA3 DG Regions of Hippocampus
PM-012 pharmacological effects from in vivo testing (3)
Confirmed enhancement of cognitive abilities of white mice

Test substance: PM-012
Test animal: Male SD rats
Method and duration of drug administration: Administered by dissolving PM-012 in 200ml of drinking water for the group
Control Group Ginko Biloba Soya Lecithin PM-012
Only drinking water 2.6mg/100g (weight) daily 100mg/100g (weight) daily 400mg/100g (weight) daily
10 days 10 days 10 days 10 days
❖ Study results
Statistically meaningful increase in memory index (retention latency) in the passive avoidance test of the Morris water maze (double the retention time compared to rats that did not receive PM-012).
Result value: 238.1±72.40s (control) vs 487.6±57.42s (PM-012),p<0.01
* Related papers: PM-012 pharmacological effects in animal testing (3)
PM-012 Mouse Memory Retention Latency
** Significantly different from control group (p<0.01)
PM-012 pharmacological effects from in vivo testing (4)
Improvement in relation to regulation of gene expression in the hippocampus
* Reference: Internal research materials
PM-012 Gene Expression
1. Increase of 94 types of genes, including IGF2, Rab3b, Sult1a1, and PTGDS
  ↳ Inhibiting effect on induction and progression of dementia

2. Increase in 43 types of catalytic activity genes, including LDHB, ATP1b1, etc.
  ↳ Enhances the mediating effects of signal transmission

3. Increase in signal transducer activity-promoting genes such as RGS14 and ITGB1
  ↳ Increases molecular binding capacity for signal transmission and provides structural protection to ribosome and myelin

4. Increase in binding factor-related genes such as MATR3, TF, etc.

1. Decrease in 68 types of genes, including DDR1, RGS14, LDHB, ATP1b1, MAL, etc.
  ↳ Inhibiting effect that causes decline in new memories
PM-012 pharmacological effects from in vivo testing (5)
Increased cognitive ability in normal human subjects (healthy individuals)
Cognitive Ability Test Control Group Test Group
Dosage: Placebo, 3 tablets/day 650mg PM-012, 3 tablets/day
Duration: 6 weeks 6 weeks
Confirmation method: 1. Administered Korean version of Wechsler Adult Intelligence Scale (WAIS), an IQ test
  2. ERP P300 brain wave measurement: confirmed cognitive function and information processing speed
PM-012 impact on IQ test
Average increase of 2 points in IQ
PM-012 impact on P300 latency
Quicker processing of external stimuli
PM-012 pharmacological effects summary
PM-012 Mouse Memory Retention Latency
Increase in glucose metabolism
Glucose adsorption
1. 67% increase in whole brain (P<0.005)
2. 62% increase in hippocampus neurogenesis (P<0.005)
Gene expression regulation
1. Regulates decrease in Pentraxin
2. Regulates increase in Transthyretin
3. Regulates increase in PEP-19
Improvement in processing information
In human testing of normal individuals:
1. Average increase of 2 points in IQ
2. Improvement in ERP300 brain wave latency
Promotion of new neurogenesis
Promotes new neurogenesis in the hippocampus' CA1, CA3 and DG areas of 3XTg-AD mice
ChAT activity
1. Recovery in ChAT activity
2. Recovery in cholinergic neurons
The Safety Aspects of PM-012
PM-012 Safety Results in Animal Testing
Oral toxicity tests of PM-012 using beagles

ChemOn Inc., preclinical laboratory, Test No.: 12-PR-653
Administration method:
Comparator group, PM-012 test group (250mg/kg/day, 500mg/kg/day, 1000mg/kg/day, 1500mg/kg/day) Administered to two male and two female beagles daily for 4 weeks
PM-012 Toxicity Test - Weight Change
No change in weight caused by the drug
PM-012 Toxicity Test - Blood Hemotological Abnormality Check
No hematological abnormalities caused by the drug
PM-012 Toxicity Test - Organ Damage Verification Check
No changes to any major organs caused by the drug