Cybin Company Presentation

Animals: 4 week-old Crl:CD1(ICR) mice, female Treatment: Mice were pretreated with AHCC at 500 mg/kg/day from day -4, and infected with methycillin-resistant Staphylococcus aureus (MRSA) at day 0. AHCC Pre - Clinical Studies P r i v a t e & C o n f i d e n t i a l Animals: 6 week-old BALB/cA mice, female (n=17 each group) Treatment: Colon-26 tumor cells were inoculated (5 x 10 ⁵ cells/mouse) 3 days before cisplatin initial injection. AHCC; 100 mg/kg/day, Cisplatin; 8 mg/kg at day 0, 6, 13, 20 Period: 28 days Measurement: Tutor size Chemotherapy Support ANIMAL Study Overview Nishioka, H. et al. Toxicology and Applied Pharmacology (2007) Days after tumor inoculation 0 10 20 30 Tumor Size (mm3 , ) 2,000 4,000 6,000 8,000 Control Cisplatin Cisplatin + AHCC *p<0.01 vs Control **p<0.01 vs Control p<0.05 vs Cisplatin Side Effects Reduction of Most Common Chemotherapy Agents ANIMAL Study Overview Animals: ddY mice, male (n=8~11 each group) Treatment: AHCC; 360~1000 mg/kg/day, anticancer drugs used per day; TAX (paclitaxel; 15~20 mg/kg), CDDP (cisplatin; 8 mg/kg), 5FU (5-fluorouracil; 100 mg/kg), CPT (irinotecan; 50 mg/kg), DXR (doxorubicin; 8 mg/kg), CY (cyclophosphamide; 120 mg/kg) Period: 25 days Measurement: bone marrow cell viability Fujii, H. et al. Journal of Experimental Therapeutics and Oncology (2009) Control Drugs Only Drugs + AHCC 150 100 50 0 *p<0.01 vs Control **p<0.01 vs Control, AHCC group Control TAX TAX+ CDDP 5FU+ CPT CDDP+ 5FU DXR+ CY Cell viability (% of control) ANIMAL Study Overview West Nile Virus Animals: 21-22 month-old C57BL/6 mice Treatment: 600 mg/kg every other day for 1 week before infection and at day 1 and 3 postinfection. 80 PFU (close to 100% lethal dose) of WNV isolate NY99 was innoculated intraperitoneally. Period: 28 days until mice showed signs of morbidity Measurement: WNV-specific IgG and viremia at day 4, and survival rate post infection Wang, T. et al. The Journal of Nutrition (2009) 100 80 60 40 20 0 AHCC (n=11) Control (n=10) Percent Survival Days post infection Survival Rate 0 4 8 12 16 20 Viremia WNV-specific IgG Control (n=8) AHCC (n=8) Control (n=10) AHCC (n=9) 100 80 60 40 20 0 0.5 0.4 0.3 0.2 0.1 0.0 *p<0.05 vs Control *p<0.05 vs Control IgG OD WNVE/β-actin x 10 ̄⁵ MRSA * * * * 100 80 60 40 20 0 AHCC 500 mg (n=8) Control (n=9) Survival Rate (%) Days post infection 0 7 14 21 28 * p<0.05 vs Control * Abe, S. et al. Yakugaku Zasshi (2000) Period: 28 days Measurement: Survival rate Intestinal Condition Improvement Animal: Wistar rats, female (200-250 g, n=6 each group) Treatment: AHCC (500 mg/kg/day) or sulfasalazine (200 mg/kg/day) to TNBS (10 mg/rat)-induced colitis rats Period: 2 days pre-colitis-induction + 6 days post-colitis-induction Measurement: colonic damage, intestinal flora Damage score 12 10 8 6 4 0 *p<0.05 vs TNBS 2 * * * Martinez-Augustin, O. et al. The Journal of Nutrition (2007) Colonic Damage 8 6 4 0 Pathogenic Clostridium 2 Log CFU A *p<0.05 vsControl Control TNBS Bifidobacteria B LacticAcid Bacteria C Sulfasalazine AHCC Intestinal Flora A A A A B B B B C C C C 21

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