Niki BioSolutions, Inc. · NASDAQ:NIKI
Niki BioSolutions — Aptorum Group — Investor Presentation (October 2019)
43 slides from Niki BioSolutions's investor presentation, Oct 25, 2019
Slide 1: Facilitating Life Science Innovations to Serve Unmet Medical Needs
PTORUM= Facilitating Life Science Innovations to Serve Unmet Medical Needs
Slide 2: Disclaimer
Disclaimer 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 forward-looking statements refer in particular to the Company's management's business s
Slide 3: SMART pipeline overview
SMART: i pipeline overview Current progress of pipeline programs -» Lead Projects -» Other Candidates Projected timeline Pillar 1: SMART-ACT™ (SACT series) - Orphan disease drug repurposing platform hi th IND Over 7,000 or] diseases to be screened in the next 5 year: , phan dise ech Inthe next 5 yea
Slide 4: In vitro drug activity against neuroblastoma cell lines IMR-32
In vitro drug activity against neuroblastoma cell lines IMR-32 ¢ 48 drug candidates were screened computationally and they were evaluated in vitro for activity validation ¢ 1 candidate, SP055, were found to provide favorable anticancer activities and the results against IMR-32 were tabulated as foll
Slide 5: Synergistic effect of SP055 in combination with standard treatment
nergistic effect of SP055 in combination with standard treatment e Synergistic effect observed for SP055 in combination with standard treatment in 2 different neuroblastoma cell lines, as measured by the Excess over Bliss Synergistic S Excess over Bliss _ Excess over Bliss 3 q 0.2 x 02 2 2 B 04 Ss 0
Slide 6: SP055: safety & tolerability
SP055: safety & tolerability FDA approved safety profile ° Did not show a genotoxic potential even at the highest feasible concentration dose (in vitro and in vivo) ° In a phase IIb study, all SP055 doses were safe and well tolerated over 96 weeks ° Most frequently reported mild adverse drug reactio
Slide 7: SP055: pharmacokinetics
Drug plasma concentration [ng/mL] ‘mo 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 ) 1/2 “0 Normalofat breakfast “> Fasted mt HighoFat breakfast “Nutritional dr
Slide 8: Acticule projects - infectious disease
APTORUM= Facilitating Life Science Innovations to Serve Unmet Medical Needs ACTICULE PROJECTS - INFECTIOUS DISEASE L ;
Slide 9: Executive summary
Executive summary: e Aptorum's lead program ALS-4 is an anti-virulent, non-bactericidal drug candidate for Staphylococcus aureus infections including MRSA‘ e Unlike all major treatments on the market’, ALS-4 relies on an anti-virulent non-bactericidal approach’, potentially reducing significant risk
Slide 10: Acticule pipeline overview
ne overview Current progress of pipeline programs -» Lead Projects -» Other Candidates Projected timeline Pillar 1: Acticule (ALS series) - Infectious diseases Small molecule, anti-virulence and non-bactericidal approach Phil/III based on Program Disc Lead optimization IND enabling a LPAD path ALS-4
Slide 11: ALS-4: mechanism of action
S-4: mechanism of actio Arorr - An, PP | on” AtAheyery el or -—————— AL s-4 Anthem 4,4'-Diapophytofluene } crtn ALS-4 4,4-Diapo-c-carotene | criy inhibits a key enzyme ° in the biosynthesis Saanor eh eas cecrearasronmecall aldH of staphyloxanthin! is naaeaneen ens 4,4"-Diaponeurosporenoic sia ertQ e
Slide 12: ALS-4: mechanism of action
ALS-4: mechanism of action DMSO Control ALS-4 & & & 200 nM & & ww ‘ bis a 100 nM ALS-4 inhibits S. aureus pigment production with an IC,, = 20nM Based on Aptorum’s internal tests/experimentation and has not yet been verified by clinical trials or third party testing. Applies to all content on this s
Slide 13: in vivo efficacy
in vivo efficacy ALS-4 inhibits S. aureus pigment production with an IC,, = 20nM ACUTE TREATMENT DELAYED TREATMENT ¥ Vehicle m ALS-4 8 2 v 2 Soy 5 = 7 ~ 2 vy cy s £ > 4 Fy e 2 vl, 2 Compound concentration: 1mM Compound concentration: 1mM Inoculum: 5X 10° per mouse Inoculum: 2X 10’ per mouse Treatmen
Slide 14: ALS-4 resistance raising in MRSA
S-4 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: 60ul overnight culture was added to 6ml BHI broth with different drugs. Clindamycin (CLI): 0.12 pg/ml; Erythromycin (ERY): 16 g/ml; ALS-4: 1
Slide 15: Resistance of S. aureus USA 300(lac) to clindamycin after various treatment conditions
Resistance of S. aureus USA 300(lac) to clindamycin after various treatment conditio Pre-treatment Day 1-4 Day 5-10 1 DMSO DMSO 2) ERY + CLI ERY (Clindamycin withdrawn between day 5-10) 5} ALS-4 ALS-4 Clindamycin resistance test after pre-treatment (BHI medium with 5 x 10*/well bacterial inoculum) 1
Slide 16: Pigment production of S. aureus with different treatments
n of S. aureus with different treatments ALS-4 efficacy test (Bacterial inoculum: 4 x 10’/ml) 08 —*- DMSO ERY +CLI 0.6 -® ALS-41uM Relative pigment production oO ‘Ss “0.01 10 100 Concentration of ALS-4 (nM) BHI agar plates No ALS-4 100nM ALS-4 (all colonies turned white) (all colonies remained yello
Slide 17: ALS-4: pharmacology & toxicology
ALS-4: pharmacology & toxicology In vitro safety screening Average % inhibition across 86 key human enzymes e Average inhibition of 17.5% across 86 key human enzymes % inhibition 8 ery: ila e Enzyme inhibition assay shows that ALS-4 has a clean profile with little off-target inhibition e Key enzymes
Slide 18: ALS-4: pharmacology & toxicology
ALS-4: pharmacology & toxicology In vitro metabolism study using liver microsomes from 5 different species 100 80 @ ALS-4 60 = Verapamil (positive control) 40 | LJ | Rat abe = Monkey Half-life (min) 8 ° e Liver microsome studies show low intrinsic clearance in 5 different species, including human. R
Slide 19: ALS-4: pharmacology & toxicology
pharmacology & toxicology Pharmacokinetics ¢ Biological half-life of ALS-4 is around 2 hours in mice (N=3). Rat pharmacokinetics study ongoing Coax (NG/ML) 12624.55 ge fou oat (NG*hr/mL) 9732 € 8 8000 AUC, (ng*hr/mL) 9927 a gs K, (hr') 0.37 “E 6000 s§ t,, (hr) 1.87 ==) oo 57 4000 Extrap AUC (%) 1.97
Slide 20: ALS-4: pharmacology & toxicology
pharmacology & toxicology Mean of negative control ------ SD of negative control GLP AMES test for mutagenicity Ce oc: ez es ats ss SSS SDSS Den pe) DOR expan) DER expe) DR spar) ‘DR gprs) Fe 1 ASE ~My + SD wer pt pit Fm 3 (TALON, - Mam cle cous = SD me aed apt et igen (APD 6) Ma cy 2 SD we lal pat
Slide 21: ALS-4 properties
ALS-4 properties Molecular weight (g/mol) 449.36 LogD' pH7.4 4.43 pka(s)" 14.5 Caco-2 permeability 2.27 x 104 cm/s (non-pgp substrate) Permeability (Human jejunum, pH 6.5) 7.39 x 10% cm/s In vitro CL (human, monkey, dog, rat, mouse liver microsomes) 94.97, 335.4, 170.92, 145.8, 180 (uL/min/mg) Plasm
Slide 22: ALS-4: chemistry, manufacturing and controls
ALS-4: chemistry, manufacturing and controls Enabling oral formulation (red) vastly improved ALS-4 bioavailability in mice 1500 -® PO enabling formulation, 87.5 mg/kg) —® PO (in 1% cme, 87.5 mg/kg) 1000 —#— IP (17.5 mg/kg) Concentration in plasma Time (hr) e The enabling oral formulation is being sc
Slide 23: ALS-4: chemistry, manufacturing and controls
ALS-4: chemistry, manufacturing and controls ALS-4 is an attractive candidate for formulation ¢ Only 1 physical form identified from polymorph screening e Physically and chemically stable e Not hygroscopic API (active pharmaceutical ingredient) manufacturing e Successfully scaled up to 200-300g batc
Slide 24: ALS-2 & ALS-3
ALS-2 & ALS-3 Additional anti-virulence, non-bactericidal therapeutics for the treatment of infections caused by Gram Positive bacteria Anti-virulence compound that suppresses multiple unrelated virulence factors in S. aureus! ALS-2 rescues mice ALS-2 reduces virulence ALS-2 reduces from MRSA infect
Slide 25: ALS-1: targeting a novel druggable target for influenza A
ALS-1: targetting a novel druggable target for influenza A ALS-1 INHIBITS INFLUENZA A NUCLEOPROTEIN (NP) ¢ NP isthe 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 26: Claves projects
PTORUM= Facilitating Life Science Innovations to Serve Unmet Medical Needs NG =" 2-2 u AVES PROJECTS SS Se ee
Slide 27: Claves pipeline overview
Claves pipeline overview Current progress of pipeline programs -» Lead Projects -» Other Candidates Projected timeline Pillar 2 : Claves (CLS series) - Microbiota Large molecule approach. Over 70 targets / indications Program Discov Lead optimization IND enabling Phase lI/Ill CLS-1 Obesity Q42019 Q2
Slide 28: CLS-1: binding to therapeutic target
CLS-1: binding to therapeutic target ° Identified key microbiota metabolite claves candidate Candidate binding of obesity- linked to obesity (therapeutic target) linked metabolite (mg/g) e Screened different candidates ae ae using the Claves platform to target A2 12.32 obesity-linked metabolite, by
Slide 29: CLS-1: efficacy in a mouse model
CLS-1: efficacy 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, acclimation High-Fat Diet High-Fat Diet + CLS-1 (2-4 weeks) ee WEEK 0 1 2 3 4 5 6 7 8 9 Collect stool and blood Sacrifice - Collect organ
Slide 30: CLS-1: weight (gram)
40 35 Weight (gram) 25 0 20 @ Group 1: High-fat diet + CLS-1 CLS-1 given to the animals CLS-1 treatment sign Significant weight 7 loss within 2 weeks 2 2 £ 5 z =) G = 40 60 Group 1 Days © Group 2: High-fat diet + control. @ _High-fat diet only The above data are based on Aptorum’s internal tests and
Slide 31: CLS-1: pharmacodynamics
: pharmacodynamics Amount of therapeutic target present in stool and in blood before and after administration of CLS-1 STOOL BLOOD 600 P=0.03 400 mmol/g umol/L 200 Before After After Week 10 Week 11 Week 13 Treatment 1 Week 2 Weeks The above data are based on Aptorum’ s internal tests and has not ye
Slide 32: CLS-1: pharmacodynamics
pharmacodynamics Cholesterol and Insulin Resistance 250 = 200 z E = 150 cx ro D = 2 = 2 100 fe} 2 = 8 s g © 50 0 Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 @ Group 1: High-fat diet +CLS-1 @ Group 2: High-fat diet + control @ High-fat diet only The above data are based on Aptorum’ s internal tes
Slide 33: CLS-1: mechanism of action
-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 @ After 2weeks ©@ Before 1.0 w 36 @ Enterococcus @ Helicobacter MMDS2 8 e °° Relative Abundanc
Slide 34: CLS-1: toxicology (gut histology and inflammatory markers)
CLS-1: toxicology (gut histology and inflammatory markers) Mucosa and Inflammatory Markers Relative expression (log) IL-la IL-6 TNFa @ Group 1: High-fat diet +CLS-1 @ Group 2: High-fat diet + control. @ High-fat diet only CLS-1 does not upregulate inflammatory markers The above data are based on Apt
Slide 35: CLS-1: toxicology (liver and renal functions)
toxicology (liver and renal functions) Liver and Renal Functions 80 0.4 60 — 03 =) 3 a 5 ‘ob = = $ 40 @ 0.2 5 < a ro < ¢ 20 9 01 0 0.0 Group 1 Group 2 Group 3 Group 1 Group 2 Group 3 @ Group 1:High-fat diet+CLS-1 @ Group 2: High-fat diet + control @ High-fat diet only CLS-1 does not interfere with l
Slide 36: CLS-1: towards clinical trials
towards clinical trials PHARMACOLOGY & PHARMACOKINETICS « Invivo non-absorbability and mass balance testing is ongoing TOXICOLOGY ° GLP toxicology (Ames test) and GLP manufacturing is under planning CHEMISTRY, MANUFACTURING & CONTROL e CLS-1is likely a non-absorbable macromolecule e Not soluble in t
Slide 37: NLS-2 projects
PTORUM= Facilitating Life Science Innovations to Serve Unmet Medical Needs
Slide 38: Executive summary
Executive summary e NLS-2is 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 e DOI significantly increased estradiol biosynthesis and aromatase expression in granulosa cells in vitro and in
Slide 39: DOI - a Chinese yam extract to address menopausal symptoms
DOI - a Chinese yam extract to address menopausal symptom DOI, a novel bioactive peptide with estrogen-stimulating activity! * Discovered an estrogen-stimulating activity from an extract obtained from the Chinese yam, Dioscorea opposita Thunb «Identified and isolated a novel bioactive component, DOI
Slide 40: DOI - a Chinese yam extract to address menopausal symptoms
DOI - a Chinese yam extract to address menopausal symptoms In in vivo rat models, DOI is shown to stimulate estradiol level and induce estrogen-related gene expressions! @ : : (b) (c) Normalized Serum Estradiol Level Apparent Trabecular Bone Bone Volume Fraction of After Treatment Mineral Density of
Slide 41: DOI and bone density
DOI - a Chinese yam extract to address menopausal symptoms DOl and bone density" * DO! in old female SD rats demonstrated an increase in the apparent bone mineral density, bone volume fraction and trabecular thickness by microCT scanning (a (b) © @ Apparent Trabecular Bone Bone Volume Fraction of Tr
Slide 42: DOI - a Chinese yam extract to address menopausal symptoms
DOI - a Chinese yam extract to address menopausal symptom 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 43: Aptorum
APTORUM