Niki BioSolutions, Inc. · NASDAQ:NIKI
Niki BioSolutions — Aptorum Group — Investor Presentation (February 2020)
49 slides from Niki BioSolutions's investor presentation, Feb 10, 2020
Slide 1: Aptorum: Facilitating Life Science Innovations to Serve Unmet Medical Needs
PTORUM Unmet Medical Needs Innovations to Serve Facilitating Life Science
Slide 2: Forward-looking statements
Certain information included in this presentation and other statements or materials published by Aptorum Group Limited (the” Company”) are not historical facts but are forward looking statements. These forwardooking statements refer in particular to the Company's management's business strategies, it
Slide 3: Current progress of pipeline programs: Pillar 1 SMART-ACT
. Current progress of pipeline programs: Lead Projects —> Other Candidates ©— > Projected timeline Note: all projected timelines refer to the estimated commencement time of the indicated stages Pillar 1: SMART-ACT™ (SACT series) - Orphan disease drug repurposing platform IND Over 7,000 orphan diseas
Slide 4: In vitro drug activity against neuroblastoma cell lines
In vitro drug activity against a cell lines * 48 drug candidate hits from the computational screen were evaluated in vitro for activity validation * 1 candidate, SP055, was found to provide favorable anticancer activities in 4 different neuroblastoma cell lines Control treatment on neuroblastoma cel
Slide 5: Synergistic effect of SP055 in combination with standard treatment
Synergistic effect of SP055 in combination with standard treatmen ° Synergistic effect observed for SP055 in combination with standard treatment in 2 different neuroblastoma cell lines, as seen in the isobologram (left) and the Excess over Bliss (right) *.. e . . Antagonism = = x e z oO Zee oO a 2 r
Slide 6: SP055: safety & tolerability
SP055: safety & tolerability FDA approved safety profile * Did not show genotoxic potential even at the highest feasible concentration dose (in vitro and in vivo) ° Ina phase Ilb study over 2 years, all SPO55 doses were safe and well tolerated ° No dose relationship between SP055 and adverse events
Slide 7: SP055: pharmacokinetics
SP055: pharmacokinetics FDA approved pharmacokinetics profile * Data package can be potentially accepted by the FDA in our 505(b)(2) new drug application * Relatively long half-life (t,. = 43-55h). Frequent dosing may not be required SP055 pharmacokinetic parameter in humans (N=19) Crap ln 5 Craw ng
Slide 8: Aptorum: Facilitating Life Science Innovations to Serve Unmet Medical Needs
APTORUM Facilitating Life Science Innovations to Serve Unmet Medical Needs
Slide 9: ALS-4 Executive summary
ALS-2/ALS-3 ti Executive summary e projec Aptorum's lead program ALS-4 is an anti-virulent, non-bactericidal drug candidate for Staphylococcus aureus infections including MRSA' Unlike all major treatments on the market?, ALS-4 relies on an anti-virulent non-bactericidal approach’, potentially reduci
Slide 10: Current progress of pipeline programs: Pillar 2 Acticule
Current progress of pipeline programs: Lead Projects. —> Other Candidates — Projected timeline Note: all projected timelines refer to the estimated commencement time of the indicated stages Pillar 2: Acticule (ALS series) — Infectious diseases* Small molecule, anti-virulence and non-bactericidal app
Slide 11: ALS-4: mechanism of action
ALS-4: mechanism of action Arore oe dab cee Pe FPP t erm Aree seemioetoene crtN -_———ALS-4 4,4-Diapophytofiuene | crt inhibits a key sarDiapo-cearetone | gry enzyme in the biosynthesis of adware 4,4*-Diaponeurosporen-4-al| argpy staphyloxanthin! yb eer 4.t-oiponeuresperencte ail ort on ©, Ho: Ho: H
Slide 12: ALS-4: mechanism of action
ALS-4: mechanism of action DMSO control ALS-4 ALS-4 inhibits S. aureus pigment production with an IC, = 20nM
Slide 13: ALS-4 is shown to be effective across strains of S. aureus
4 is shown to be effective across 11 strains of S. aureus ALS-4 is believed to inhibit the production of staphyloxanthin in 11 strains of S. aureus in vitro Strain Type ICs (nM) ° $H1000 MSSA 70.546 z HG003 MSSA 54.444 . USA300-JE2 MSSA 37744 2 USA300 (FPR-3757) CA-MRSA 30.845 3 USA300-3 HA-MRSA 42.
Slide 14: ALS-4 increases sensitivity of S. aureus to oxidative damage
ALS-4 is shown to increase sensitivity of S. aureus to oxidative damage ALS-4 is believed to reduce bacteria number by an additional 10-fold in the presence of hydrogen peroxide EE) Control ES ALS-4 (2uM) 1.010'° 1.010°° 1.0.10°° 1.010% CFU/ mL 1.0x10°? 1.0x10°° The results shown in this slide are b
Slide 15: ALS-4: in vivo efficacy
4: in vivo efficacy ALS-4 inhibits S. aureus pigment production with an IC,;, = 20nM Acute treatment Delayed treatment * v Vehicle i ALS-4 8 rr | 8 CFU/Kidney in log scale < < CFU/Kidney in log scale ALS-4 concentration: 1mM ALS-4 concentration: 1mM Inoculum: 5 x 106 per mouse Inoculum: 2 x 10” per
Slide 16: ALS-4: oral formulation
4: oral formulatio Enabling oral formulation (red) vastly improved ALS-4 bioavailability in mice 1500 = -® PO (enabling formulation. 87.5 mg/kg) s A PO in 1% ome, 87.5 maiko) o ~ = 1000 IP (17.5 moika) a | © iJ £ So s c = ° ry e ° oO Time (hr) * The enabling oral formulation is being scaled up and s
Slide 17: ALS-4: oral formulation treatment in an MRSA survival study
ALS-4: oral formulation treatment in an MRSA survival study ALS-4 rescues rats infected with a lethal dose of MRSA USA300 in a bacteremia model 100 =® Vehicle (N=9) = ALS-4 (10mg/kg) (N=9) 50 Survival (%) Time (d) ¢ Alethal dose (102 CFU) of MRSA was introduced through the tail vein ° ALS-4 was admi
Slide 18: ALS-4: oral formulation treatment in a non-lethal bacteremia model
ALS-4: oral formulation treatment in a non-lethal bacteremia model ALS-4 is shown to greatly reduce organ bacterial count in a bacteremia animal model 8 | 10*8 = 63,096 CFU/g Kidney bacterial count (CFU/g) (logis scale) 4 99.5%reduction 1025 = 316 CFU/g Control ALS-4 (N=8) (10mg/kg) (N=8) * Rats wer
Slide 19: ALS-4 does not directly inhibit bacterial growth in vitro
ALS-4 is shown not to directly inhibit bacterial growth in vitro Lack of direct selection pressure makes it unlikely for drug resistance to emerge Does not inhibit in growth in 5 strains of S. aureus (left) and 6 different species of bacteria (right) 1.5 3. ss > E.coli 3 1.0 2 A, baumamii 5 ste S. c
Slide 20: ALS-4 does not interfere with the action of vancomycin
ALS-4 does not interfere with the action of vancomycin ALS-4 does not affect the minimum inhibitory concentration (MIC) of vancomycin in 8 strains of S. aureus Clinical isolate ST23911I (RKC504) ATCC29213 (RKC323) Mu3 (RKC329) HG003 (RKC723) Wel) so 25 12 6 3 15 O8 04 02 01 005 0 ei) so 25 12 6 3 18
Slide 21: Resistance raising in MRSA
resistance raising in MRSA Protocol 1. Inoculum preparation: USA300-3 (LAC) was cultured overnight in BHI broth at 37°C, 250 rpm. 2. Subculture preparation: 60 yl overnight culture was added to 6 ml BHI broth with different drugs. 1 DMSO DMSO 2 Ery 16 + CLI 0.12 pg/ml Ery 16 3 ALS-4 1uM ALS-4 1uM 3.
Slide 22: Resistance of S. aureus USA300 to clindamycin after treatment conditions
Resistance of S. aureus USA 300(lac) to clindamycin after various treatment conditions Pre-treatment atl DMSO DMSO 2 Ery 16 + CLI 0.12 pg/ml Ery 16 (Clindamycin withdrawn between day 5-10) 3 ALS-4 1uM ALS-4 14M Clindamycin resistance test after pre-treatment (BHI medium with 5 x 104/well bacterial i
Slide 23: ALS-4 efficacy test: no resistance detected
ALS-4 efficacy test BHI agar plates 100nM ALS-4 No ALS-4 (all colonies turned white) (all colonies remained yellow) A y (Bacterial inoculum: 4 x 107/ml) ° @ Recovered bacteria eo -4- ALS-4-1uM after 11-day resistance- Ery16-Cli0.12 ug/ml raising with 1M ALS-4 —- DMSO Recovered bacteria after 11-day
Slide 24: ALS-4: pharmacology & toxicology
ALS-4: pharmacology & toxicology In vitro safety screening Average % inhibition across 86 key human enzymes 110 90 70 50 3 8 % inhibition eT S -10 30 -50 « Average inhibition of 175% across 86 key human enzymes « Enzyme inhibition assay shows that ALS-4 has a clean profile with little off-target inh
Slide 25: ALS-4: pharmacology & toxicology
ALS-4: pharmacology & toxicology In vitro metabolism study using liver microsomes from 5 different species 100 80 60 mALS-4 40 | ™ Verapamil (positive control) 2 Human Mice Monkey Half-life (min) 8 ° ° Liver microsome studies show low intrinsic clearance in 5 different species, including human. Resu
Slide 26: ALS-4: pharmacology & toxicology
ALS-4: pharmacology & toxicology Pharmacokinetics * Biological half-life of ALS-4 is around 2 hours in mice (N=3). Rat pharmacokinetics study ongoing Cyr, (g/mL) 12624.55 10000 : tux (ng*hr/mL) 9732 s 8000 ,_. (ng*hr/mL) 9927 = : el K, (hr?) 0.37 = 2 6000 eg tye (hr) 1.87 = 4000 Extrap AUC (%) 1.97
Slide 27: ALS-4: pharmacology & toxicology
ALS-4: pharmacology & toxicolog Results for Plate Incorporation Assay GLP AMES test for mutagenicity Legend: Mean of negative control: ‘SD of negative control: De cpa) AB cepa) oc: 02 3 cs os a ‘pe 3. TAL) -Me oley cous SD me ned ap ‘Bip 5 TALS, 9) - Macey comm = SD we ol pa he mitt Hl t z fe Doserp
Slide 28: ALS-4 properties
ALS-4 properties Molecular weight (g/mol) LogD' pH7.4 pka(s)' Caco-2 permeability Permeability (Human jejunum, pH 6.5) In vitro CL (human, monkey, dog, rat, mouse liver microsomes) Plasma protein binding" DDI risk (CYP450 reversible inhibition, TDI and induction) Calculated properties using ACD/Labs
Slide 29: ALS-4: chemistry, manufacturing and control
4: chemistry, manufacturing and co ALS-4 is an attractive candidate for formulation * Only 1 physical form identified from polymorph screening * Physically and chemically stable * Not hygroscopic API (active pharmaceutical ingredient) manufacturing * Successfully scaled up to 200-300g batch * GLP to
Slide 30: ALS-2 & ALS-3
ALS-2 & ALS-3 Additional anti-virulence, non-bactericidal therapeutics for the treatment of infections caused by Gram Positive bacteria S-2 Anti-virulence compound that suppresses multiple unrelated virulence factors in S. aureus! ALS-2 rescues mice ALS-2 reduces virulence ALS-2 reduces bacterial fr
Slide 31: ALS-1: targeting a novel druggable target for Influenza A
ALS-1: targeting a novel druggable target for Influenza A ALS-1 inhibits influenza A nucleoprotein (NP) * NP is the most abundantly expressed protein during the course of an infection’. Its primary function is to encapsidate the virus genome for RNA transcription, replication and packaging. It is al
Slide 32: Aptorum: Facilitating Life Science Innovations to Serve Unmet Medical Needs
PTORUM= Facilitating Life Science Innovations to Serve Unmet Medical Needs —J . e —— a ) > PROJECTS lh ee ee rn ee WN 3 ‘ 4 ~~ " — 2. A : . . ‘ s A\Y , ¢ (% 2)
Slide 33: Current progress of pipeline programs: Pillar 3 Claves
Current progress of pipeline programs: Lead Projects — > Other Candidates —> Projected timeline Note: all projected timelines refer to the estimated commencement time of the indicated stages Pillar 3: Claves (CLS series) - Microbiota Large molecule approach. Over 70 targets / indications IND Program
Slide 34: CLS-1: binding to therapeutic target
CLS-1: binding to therapeutic target : Candidate binding of obesity- Claves Candidate linked metabolite (mg/g) * Identified key microbiota metabolite linked to obesity (therapeutic target) Al 2.42 * Screened different candidates using the Claves 2 12.32 platform to target obesity-linked metabolite,
Slide 35: CLS-1: efficacy in a mouse model
icacy in a mouse model Experimental outline to test efficacy of CLS-1 treatment (orally available, non-absorbable) in mice on a high-fat diet Chow Diet, . | oh. . : acclimation High-Fat Diet High Fat Diet + CLS-1 er WEEK 0 1 Collect stool and blood Sacrifice - Collect organs, stool and blood @ Group
Slide 36: CLS-1: efficacy in a mouse model
CLS-1: efficacy in a mouse model CLS-1 treatment significantly reduces body weight in mice 40 CLS-1 given to the animals _ 35 Significant weight = € loss within 2 weeks 2 & rm = 4 = s = Ss) o] 2 = = 30 2 = 25 0 20 40 60 Group 1 Group 2 Group 3 Days @ Group 1: High-fat diet +CLS-1 @® Group 2:High-fat
Slide 37: CLS-1: pharmacodynamics
mmol/g Cc Amount of therapeutic target present in stool and in blood before and after administration of CLS-1 -1: pharmacodynamics STOOL BLOOD 600 P=0.03 400 = [oy = 3 200 0 Before After After Week 10 Week 11 Week 13 Treatment 1Week 2 Weeks Based on Aptorum's internal tests/experimentation and has n
Slide 38: CLS-1: pharmacodynamics, cholesterol and insulin resistance
Total cholesterol (mg/dL) 250 200 150 100 50 Group 1 CLS-1: pharmacodynamics Cholesterol and Insulin Resistance HOMA-IR Group 2 Group 3 @ Group 1: High-fat diet+CLS-1 @® Group 2: High-fat diet + control Group 1 Group 2 @ High-fat diet only Group 3
Slide 39: CLS-1: mechanism of action
CLS-1: mechanism of action CLS-1 induced progressive changes CLS-1 may act by promoting Akkermansia proliferation, in the microbiota a species of beneficial gut bacteria linked to obesity!?? 40 ° @ After 1 week a @ After 2weeks @ Before N w S So MMDS2 e ° Relative Abundance (%) 1. Cani PD et al. Nat
Slide 40: CLS-1: toxicology (gut histology and inflammatory markers)
toxicology (gut histology and inflammatory markers) Mucosa and Inflammatory Markers @ Group 1: High-fat diet +CLS-1 @ Group 2: High-fat diet + control @ High-fat diet only Relative expression (log) IL-1a Il-6 TNFa CLS-1 does not upregulate inflammatory markers Based on Apt (0 all content on this sli
Slide 41: CLS-1: toxicology (liver and renal functions)
ALT Level (U/L) 80 a c) =~ So N i=) Group 1 CLS-1: toxicology (liver and renal functions) Liver and Renal Functions Creatinine (mg/dL) Group 2 Group 3 Group 1 CLS-1 does not interfere with liver and renal functions Group 2 Group 3
Slide 42: Towards Clinical Trials
Towards Clinical Trials Pharmacology & Pharmacokinetics * In vivonon-absorbability and mass balance testing is under planning Toxicology * Non-GLP Ames test indicates CLS-1 is not mutagenic Chemistry, Manufacturing & Control * CLS-1 is likely a non-absorbable macromolecule » API manufacturing proces
Slide 43: Aptorum: Facilitating Life Science Innovations to Serve Unmet Medical Needs
PTORUM= Facilitating Life Science Innovations to Serve Unmet Medical Needs
Slide 44: NLS-2: Executive Summary
NLS-2: Executive Summary * NLS-2 is a dietary supplement for the relief of menopausal symptoms. * The bioactive component of NLS-2 is DOI, a novel non-hormonal compound extracted from Chinese Yam * DOI significantly increased estradiol biosynthesis and aromatase expression in granulosa cells in vitr
Slide 45: DOI - a Chinese yam extract to address menopausal syndrome
DOI- a Chinese yam extract to address menopausal syndrome DOI, a novel bioac' » Discovered an estrogen-stimulating activity from an extract obtained from the Chinese yam, Dioscorea opposita Thunb e peptide with estrogen-stimulating activity’ * Identified and isolated a novel bioactive component, DOI
Slide 46: DOI - in vivo rat model results
DOI- a Chinese yam extract to address menopausal syndrome In in vivo rat models, DOI is shown to stimulate estradiol level and induce estrogen-related gene expressions! @ (b) (c) Normalized Serum Eatrestol Level Apparent Trabecular Bone Bone Volume Fraction of ial Mineral Density of Vertebra L2 Vert
Slide 47: DOI and bone density
DOI- a Chinese yam extract to address menopausal syndrome DOI and bone density" * DOl in old female SD rats demonstrated an increase in the apparent bone mineral density, bone volume fraction and trabecular thickness by microCT scanning (b) ©) (d) Apparent Trabecular Bone Bone Volume Fraction of Tra
Slide 48: DOI toxicity in vitro (MTT assay)
DOI- a Chinese yam extract to address menopausal syndrome DOI does not cause toxicity in vitro based on cell viability in the MTT assay’ * DOI demonstrated the decrease in viability of MCF-7 breast cancer cells and OVCA-429 ovarian cancer cells, indicating that DOI is not expected to display any of
Slide 49: Aptorum Group Limited investor relations
PTORUM= APTORUM GROUP LIMITED investor.relations:
Aptorum Group — Investor Presentation (February 2020) on 6ix