Exhibit 99.1
Facilitating Life Science Innovations to Serve Unmet Medical Needs CORPORATE PRESENTATION NASDAQ GLOBAL MARKET: APM
Disclaimer 2 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited This document includes statements concerning Aptorum Group Limited and its future expectations, plans and prospects that constitute “forward - looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. For this purpose, any statements contained herein that are not statements of historical fact may be deemed to be forward - looking statements. In some cases, you can identify forward - looking statements by terms such as “may,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “target,” “projects,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” or “continue,” or the negative of these terms or other similar expressions. Aptorum Group has based these forward - looking statements, which include statements regarding projected timelines for application submissions, trials and commercialization and market potential of related products, largely on its current expectations and projections about future events and trends that it believes may affect its business, financial condition and results of operations. These forward - looking statements speak only as of the date of this document and are subject to a number of risks, uncertainties and assumptions including, without limitation, risks related to its announced management and organizational changes, the continued service and availability of key personnel, its ability to expand its product assortments by offering additional products for additional consumer segments, development results, the company’s anticipated growth strategies, anticipated trends and challenges in its business, and its expectations regarding, and the stability of, its supply chain, and the risks more fully described in Aptorum Group’s Form 20 - F and other filings that Aptorum Group may make with the SEC in the future. As a result, the projections included in such forward - looking statements are subject to change. Aptorum Group assumes no obligation to update any forward - looking statements contained in this document as a result of new information, future events or otherwise.
About Aptorum Group • Established in 2010, focused on current unmet medical needs, including orphan diseases, infectious diseases, metabolic diseases and women’s health, over 15 therapeutic candidates • Business Strategy: From Discovery to Ph2 Proof - of - Concept (PoC) • Markets and Regulatory: Targeted for US FDA clinical, China NMPA and Europe EMA approval and other major countries • IPO: Listed on NASDAQ Global Market (ticker symbol: APM) on December 18, 2018 • 2 Development Sites: Hong Kong Science and Technology Park (non - GLP, formulation, preclinical work) and Toronto (GLP, GMP, clinical trial coordination) • ~40 full time staff and ~45 scientists, advisors and consultants with vast experience in drug development and clinical studies Company information 3 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Aptorum Management and Directors • Over 15 years in global asset management; • US healthcare equity research analyst at Janus Henderson Group; • Trustee board member of Dr. Stanley Ho Medical Development Foundation; • CFA, Princeton University, U.S. (Econ) Leadership MR. IAN HUEN Founder, Chief Executive Officer and Executive Director MR. DARREN LUI President and Executive Director DR. CLARK CHENG Chief Medical Officer and Executive Director • Over 13 years in global capital market; • Extensive experience in Investment in UK, Singapore, US, etc.; • ICAS, CFA & Associate of Chartered Institute of Securities & Investments (UK); • First - Class Honors from Imperial College (Biochemistry) • Almost 10 years working in Raffles Medical Group as Operations Director and Deputy General Manager; • Received medical training at the University College London in 2005 & obtained membership of the Royal College of Surgeons of Edinburgh in 2009; • MBA, University of Iowa, U.S. MISS SABRINA KHAN Chief Financial Officer • Almost 10 years serving US & Asian healthcare companies; • Extensive experience in business development, restructuring, US & Asian IPO, and M&A deals; • Solid accounting experience gained from Big 4; • Advanced China Certified Taxation Consultant; • CPA, University of Hong Kong (BBA(Acc & Fin)) Independent Non - Executive Directors DR. THOMAS LEE WAI YIP 4 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited Head of Research and Development DR. ANGEL NG SIU YAN Chief Operating Officer • Former Assistant Professor at The Chinese University of Hong Kong (CUHK) specialized in drug delivery and formulation development; • 10 years from Novartis & Celgene; • B.Pharm.(Hons), CUHK; Ph.D. in Pharmaceutical Sciences (Drug Delivery), the University of Wisconsin - Madison • Research Officer cum Project Manager at The University of Hong Kong (HKU) towards cadaveric trial for a novel soft robotics medical device; • Former Project Manager at Hong Kong Science & Technology Parks Corporation and CUHK; • B.Sc (Hons), HKU; M.Sc in Composite Materials, Imperial College London; Ph.D. in Mechanical Engineering, HKU PROFESSOR DOUGLAS ARNER Kerry Holdings Professor in Law, HKU DR. JUSTIN WU COO of CUHK Medical Centre DR. MIRKO SCHERER CEO of CoFes China MR. CHARLES BATHURST Founder of Summerhill Advisors Limited
Aptorum Team Clinical Advisor DR. NISHANT AGRAWAL Senior Clinical Advisor - ATL DR. HENRY CHAN LIK YUEN Senior Clinical Advisor - ATL DR. PHILIP W.Y. CHIU Senior Advisor - ATL DR. VINCENT MOK CHUN TONG Senior Advisor - ATL • Professor of Surgery, School of Medicine, University • Associate Dean, Faculty of Medicine, CUHK of Chicago • Professor, Department of Surgery, Institute of Digestive Disease, CUHK • Head of Division of Neurology, Dept of Medicine & Therapeutics, CUHK Consultants, Advisors and Principal Investigators DR. KEITH CHAN Consultant • Adjunct professor and advisor at the Research Center for Drug Discovery, National Yang Ming University in Taipei; • Former Division Director of Office of Generic Drugs, US FDA; • Co - founder of Globomax LLC; • Formerly employed at Ciba - Geigy DR. LAWRENCE BAUM Senior Scientific Advisor - VIL • Hon. Asso. Professor, Department of Psychiatry, The University of Hong Kong DR. FRANCIS SZELE Senior Scientific Advisor - VIL • Asso. Professor, Department of Physiology, Anatomy & Genetics, University of Oxford; • Asst. Professor, Subventricular Zone, Northwestern University; • Ph.D. in Biology, The University of Pennsylvania, U.S. PROFESSOR RICHARD KAO Principal Investigator • Asso. Professor, Department of Microbiology, The University of Hong Kong; • Ph.D. in Microbiology, the University of British Columbia; • The recipient of the Innovation Academy Award from the International Consortium of Prevention and Control of Infection (ICPIC) in Geneva, Switzerland in 2017 MR. WILLIAM WEISS Consultant • Currently Director of Preclinical Service and Instructor of Pharmaceutical Sciences, College of Pharmacy, University of North Texas; • 38 years of experience in drug discovery and development of antimicrobials including antibiotics, antivirals and antifungals; • Former Director of Cumbre Pharmaceuticals Inc; • Former Group Leader at Wyeth for 17 years; • Formerly employed at Schering - Plough for 7 years; • BSc in Microbiology from Rutgers University; MSc in Microbiology from Penn State University and Fairleigh Dickinson University DR. KIRA SHEINERMAN 5 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited Senior Strategic Consultant • Co - Founder, CEO and Executive Director of DiamiR Biosciences; • Serves as a Managing Director, Healthcare Investment Banking at H.C. Wainwright & Co.; • Ph.D. in Biomedical Sciences from Mount Sinai School of Medicine in New York • Honors MBA from Zicklin School of Business, Baruch College, City University of New York
Current progress of leading pipeline programs and discovery 1. Refers to the drug’s existing Phase I/II safety data previously conducted by a third party. Does not refer to clinical trials conducted by Aptorum 2. Subject to FDA’s approval 6 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Current progress of leading pipeline programs and discovery 7 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
SMART - ACT ™ Drug Discovery Platform: Orphan Disease Focus and Selection Life threatening disease High unmet need IP protection Market size Competitive landscape Clinical trial design Paediatric disease By region Target selection Disease knowledge Disease selection criteria High p ri o rity • US: <200,000 patients • EU: <5 in 10,000 • Japan: <50,000 patients • China: defined list of 121 rare diseases 7000+ Orphan Diseases Patient population definition: SMART - ACT ™ High Priority Orphan Diseases 8 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
SMART - ACT ™: Pipeline Workflow 2,600 FDA - approved small molecule drugs New drug indication • Life threatening disease • Lack of effective treatment • Large market size 1 Drug target selection • Computational mining from literature • Up to 5 disease drug targets selected 2 3 In vitro validation • Cell line model • IC 50 • Combo treatment standard therapy 5 Wet lab Computational In vivo validation • Animal model • In vivo efficacy 6 IP protection • Indication patent • Reformulation • Combination patent • Dosage patent 7 Development / out - licensing • US FDA 505 (b)( 2 ) filing • In - house development or out - licensing with co - development partners 8 In silico generated hits 4 9 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
SACT - 1 (neuroblastoma): market overview SACT - 1 targets neuroblastoma, a cancer that develops from nerve cells Prevalence • ~700 cases of high risk neuroblastoma (NB) patients each year in the US 3 and we estimated EU has 1.5x those cases, c. 1050 high risk NB patients per year. • Accounts for ~15% of all cancer - related deaths in the pediatric population 4 Orphan drug designation 5 • Neuroblastoma is a rare disease and drugs are qualified for orphan designation by the FDA • Designated orphan drugs receive 7 years of market exclusivity in US and 10 years of marketing exclusivity in EU • Patents on reformulation, if granted, will provide up to 20 years of patent exclusivity from the application date in parallel to the market exclusivity 1. Pediatr Rev . 2018 Feb ; 39 ( 2 ) : 57 - 67 ; 2 . “Neuroblastoma Market Global Industry Perspective, Comprehensive Analysis, Size, Share, Growth, Trends, and Forecast 2019 – 2023 ”( 2019 ) . MRFR Research . 3 . Curr Oncol Rep . 2009 Nov ; 11 ( 6 ) : 431 - 8 4 . Paediatr Drugs . 2011 Aug 1 ; 13 ( 4 ) : 245 - 55 5 . https : //www . fda . gov/about - fda/office - special - medical - programs/office - orphan - products - development All conclusory statements on this slide are based on Aptorum’s internal tests/experimentation and has not yet been verified by clinical trials or third party testing. 10 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
In vitro drug activity against neuroblastoma cell lines • SACT - 1’s potential action against neuroblastoma might be patentable • We find that its action against neuroblastoma could be patentable The results shown in this slide are based on Aptorum's internal (in vitro/in vivo) tests/experiments that have not been verified in clinical trials and/or third party testing IC 50 [µM] IC 50 [µM] IC 50 [µM] IC 50 [µM] For IMR - 32 For SK - N - BE(2) For SK - N - SH For SH - SY5Y SACT - 1 2.97 3.37 2.75 3.12 Control treatment on neuroblastoma cells SACT - 1 treatment on neuroblastoma cells T i m e l i ne 11 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Synergistic effect of SACT - 1 in combination with standard treatment • Synergistic effect observed for SACT - 1 in combination with standard treatment in 2 different neuroblastoma cell lines, as seen in the isobologram (left) and the Excess over Bliss (right) 14 13 1 1 18 21 2 0 0.37 10 0.2 0.4 Standard Tx (μM) 1.11 3.33 SACT - 1 (μM) Neuroblastoma cell line #1 Excess over Bliss 10 13 5 0 11 9 2 - 7 0.37 10 0.2 0.4 Standard Tx (μM) 1.11 3.33 SACT - 1 (μM) Neuroblastoma cell line #2 Excess over Bliss Synergistic Antagonistic Standard Tx (μM) 12 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited SACT - 1 (μM) Synergism An t a g on i sm The results shown in this slide are based on Aptorum's internal (in vitro/in vivo) tests/experiments that have not been verified in clinical trials and/or third party testing
SACT - 1: safety & tolerability 13 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited Well - established Safety profile based on a FDA approved product • Did not show genotoxic potential even at the highest feasible concentration dose ( in vitro and in vivo ) • In a phase IIb study over 2 years, all SACT - 1 doses were safe and well tolerated • No dose relationship between RPV and adverse events (AE) Ref: doi: 10.1089/AID.2011.0050 RPV 2 5 m g /d a y (N=93) 7 5 m g /d a y (N=95) 1 5 0m g /d a y (N=91) Median treatment duration, weeks 101 100 100 Adverse events (AE) Any grade 2 - 4 AE at least possibly related to RPV 20% 20% 21% AEs leading to discontinuation 9% 12% 14% Any serious AE 13% 14% 10% Deaths 0% 2% 0% 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 = 43 - 55h). Frequent dosing may not be required
Executive summary: Acticule projects • Aptorum's lead program ALS - 4 is an anti - virulent, non - bactericidal drug candidate for Staphylococcus aureus infections including MRSA 1 • Unlike all major treatments on the market, ALS - 4 is an orally administered anti - virulent molecule using a non - bactericidal approach 1 , potentially reducing significant risks of developing S. aureus resistance • Targeting IND submission by H2 2020 • Upon IND approval, a Phase I clinical study to commence in H2 2020 in North America • Targeting to submit written request for approval under the newly established LPAD regulatory pathway (Limited Population Pathway for Antibacterial and Antifungal Drugs), to expedite marketing approval and commercialization 1. Based on Aptorum's internal tests/experimentation and has not yet been verified by clinical trials or third party testing; 2. Influenza Antiviral Medications: Summary for Clinicians. CDC. https ://www.cdc.gov/flu/professionals/antivirals/summary - clinicians.htm; 3. Nat Biotechnol. 2010 Jun;28(6):600 - 5 ALS - 4 • A unique antiviral therapeutic against Influenza A that has a more upstream target than Tamiflu ® which is shown to be more effective in vitro 1 • Viral resistance to Tamiflu and other neuraminidase inhibitors has risen rapidly in recent years 2 • ALS - 1 has a distinct mechanism of action compared with Tamiflu ® and Xofluza TM1,3 AL S - 1 ALS - 2/ALS - 3 14 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited • Additional novel anti - virulent, non - bactericidal approach therapeutics targeting Gram - positive bacteria 1 • In discovery/lead optimization stage and generating good traction towards doing IND - enabling studies 1
ALS - 4: Market Overview ALS - 4 is an anti - virulent, non - bactericidal drug candidate for Staphylococcus aureus infections including MRSA 1. Clin Microbiol Rev. 2012 Apr;25(2):362 - 86; 2. "Methicillin - resistant Staphylococcus Aureus (MRSA) Drugs Market - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 2017 - 2025“ (2018). Transparency market research; 3. https://dealbook.nytimes.com/2014/12/08/merck - agrees - to - acquire - drug - maker - cubist - for - 9 - 5 - billion/; 4. https ://www.prnewswire.com/news - releases/roivant - sciences - and - intron - bio - sign - licensing - dealfornovel - anti - superbugs - biologic - sal200 - 3 00753307.html Third - party infectious disease drugs or company - related mergers and acquisitions • In 2014, Merck's acquisition of Cubist Pharmaceuticals, a large developer of antibiotics, for USD 8.4bn 3 • In 2018, Roivant's licensing of Intron's Phase II asset for USD 667.5m in upfront and milestone payments 4 15 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Market Approved Drugs for MRSA Infections 16 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited Frequently prescribed antibiotics for MRSA infections 1 Product (Compa n y ) Antibiotic Class Indication(s) RoA Dose Cost of Treatment (duration) Notes V a n c o my c in (Generic) Glycopeptide Severe infections caused by MRSA IV / oral* 2g/day USD 101 - 144 (7 - 10 days) • Currently, the most frequently prescribed antibiotic for MRSA suspected infections 1,2 • In clinical use for >60 years 3 , vancomycin - resistant S. aureus (VRSA) was first discovered in 2002 4 Da p t o my c in (Merck) Lipopeptide ABSSSI, S. aureus bacteremia IV 4 - 6mg/kg/day USD 6,736 - 23,710 5 (14 - 42 days) • In clinical use since 2003 6 • Daptomycin resistance described in S. aureus as early as 2006 7 Li n e z olid (Pfizer) Oxazolidinone ABSSSI, CABP, HABP, uSSSI IV / oral 0.8 - 1.2g/day IV: USD 1,920 - 5,376 Oral: USD 2,978 - 11,429 (10 - 14 days) • In clinical use since 2003 8 . Entirely synthetic, not expected to develop clinical resistance 9 , however • Linezolid resistance encountered clinically since 2010 9 C e f t a r oli n e fosamil (Actavis) Cephalosporin ABSSSI, CABP IV 1.2g/day USD 1,831 - 5,127 (5 - 14 days) • In clinical use since 2010 10 • Ceftaroline resistance encountered clinically since 2016 11 Ti g ec y c li n e (Pfizer) Glycycycline ABSSSI, CABP, CIAI IV 0.1 - 0.2mg/day USD 1,888 - 4,977 (5 - 14 days) • In clinical use since 2005 12 • Tigecycline resistance encountered clinically in developing countries since 2017 13,14 Televancin (T h e r a v a n c e Biopharma) Lipoglycopeptide ABSSSI, HABP, VABP IV 10mg/kg/day USD 3,002 - 10,568 (7 - 21 days) • In clinical use since 2009 15 • Vancomycin resistance leads to a 4 - 8x increase in telavancin MIC (minimum inhibitory concentration) 16 ABSSSI: acute bacterial skin and skin structure infection; CABP: community - acquired bacterial pneumonia; HABP: hospital - acquired bacterial pneumonia; CIAI: complicated intra - abdominal infection; VABP: ventilator - associated bacterial pneumonia; * Only for intestinal infections; 1. Reproduced from“ Companies Take Aim at MRSA Infections” P T. 2016 Feb; 41(2): 126 – 128; 2. Clin Infect Dis. 2011 Feb 1;52(3):e18 - 55; 3. Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S5 - 12; 4. Centers for Disease Control and Prevention. https ://www.cdc.gov/hai/settings/lab/vrsa_lab_search_containment.html; 5. Cost of treatment of Daptomycin for S. aureus bacteremia at a dosage of 6mg/kg; 6. FDA. https:// www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21 - 572_Cubicin.cfm; 7. Int J Antimicrob Agents. 2006 Oct;28(4):280 - 7; 8. FDA. https:// www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21 - 130s003_21131s003_21132s003_ZyvoxTOC.cfm; 9. Pharmaceuticals (Basel). 2010 Jul; 3(7): 1988 – 2006; 10. FDA. https ://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/200327orig1s000toc.cfm; 11. J Antimicrob Chemother. 2016 Jun; 71(6): 1736 – 1738; 12. FDA. https:// www.accessdata.fda.gov/drugsatfda_docs/nda/2005/21 - 821_Tygacil.cfm; 13. New Microbes New Infect. 2017 Sep; 19: 8 – 12; 14. Journal of Microbiology and Infectious Diseases 2017; 7 (4):173 - 177; 15.FDA. https ://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022110s000TOC.cfm; 16. Clin Infect Dis. 2015 Sep 15;61 Suppl 2:S58 - 68.
ALS - 4: Addressing the Shortfall of Vancomycin 1. “Companies Take Aim at MRSA Infections” P T. 2016 Feb; 41(2): 126 – 128; 2. Clin Infect Dis. 2011 Feb 1;52(3):e18 - 55; 3. Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S5 - 12; 4. Antimicrob Agents Chemother. 2008 Jan;52(1):192 - 7; 5. Clin Infect Dis. 2007 Jan 15;44(2):190 - 6; 6. Clin Infect Dis. 2007 Sep 1;45(5):601 - 8; 7. J Clin Microbiol. 2011 Oct;49(10):3669 - 72; 8. Clin Infect Dis. 2007 Sep 15;45 Suppl 3:S191 - 5; 9. J Clin Microbiol. 2004 Jun;42(6):2398 - 402; 10. Centers for Disease Control and Prevention. https ://www.cdc.gov/hai/settings/lab/vrsa_lab_search_containment.html; 11. J Infect. 2018 Dec;77(6):489 - 495; 12. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 - 2018 Nov 18; 13. HealthJade, https://healthjade.net/vancomycin/ ; 14. Medscape, https://reference.medscape.com/drug/firvanq - vancocin - vancomycin - 342573; 15.Combination Antibiotic Treatment of Serious Methicillin - Resistant Staphylococcus aureus Infections, https:// www.thieme - connect.com/products/ejournals/pdf/10.1055/s - 0034 - 1396906.pdf; 16. J Clin Microbiol. 2016 Mar; 54(3): 565 – 568 Vancomycin • Generic antibiotic that is the most frequently prescribed for MRSA - suspected infections 1,2 • After >60 years 3 of clinical use, its use against S. aureus is becoming limited. Vancomycin has been shown to have slow bactericidal activity, poor anti - staphylococcal activity, poor tissue penetration, and high rates of infection relapse 4,5,6,7,8,9 • The shortcomings of Vancomycin has been compounded since the discovery of vancomycin - resistant S. aureus (VRSA) in 2002 10 • Vancomycin is not orally bioavailable and must be administered intravenously in order to treat systemic infections 11,12 . Oral vancomycin is only effective for treating local intestinal infections 13 . Therefore, for MRSA - suspected infections oral vancomycin is only indicated for the treatment of pseudomembranous colitis 14 ALS - 4: Stand Alone or as Combination Therapy with Antibiotics (e.g. Vancomycin) • As a combination therapy believed to overcome the shortcomings of vancomycin. 15 • ALS - 4 can potentially complement other bactericidal antibiotics as well, therefore ALS - 4 is not a direct competitor of antibiotics • Synergistic effects of other drugs with vancomycin against MRSA has been demonstrated previously with β - lactam antibiotics and vancomycin 16 • Awarded to the Company's Hong Kong team, led by Dr. Richard KAO • For the revolutionary concept of applying chemical genetics to tackle MRSA infection, which forms the scientific basis of ALS - 2, ALS - 3 and ALS - 4 1 st place, Innovation Academy Category, ICPIC 2017 17 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Antibiotics ALS - 4: Value Proposition • Antibiotic resistance in S. aureus has been discovered in most prescribed antibiotics for MRSA 1 • Broad spectrum and indiscriminate 2 • Commonly affect normal flora, may lead to superinfection in case of drug resistance 3 Indiscriminate clearance 1. Refer to “ALS - 4: Approved Drugs for MRSA Infections” for complete set of sources; 2. P T. 2016 Feb; 41(2): 126 – 128; 3. J Infect Dis. 2018 Jan 30;217(4):628 - 636; 4. Based on Aptorum's internal tests/experimentation and has not yet been verified by clinical trials or third party testing; 5. MBio. 2017 Sep 5;8(5). pii: e01224 - 17; 6. J Exp Med. 2005 Jul 18;202(2):209 - 15. Antibiotic Anti - virulence x Not bactericidal, potentially less selective pressure and much less likely for bacteria to develop resistance 4,5 x "Disarms" the bacteria by reducing pathogenicity 4,5,6 x Bacterial clearing is mediated by host immunity 4,5 Directed against pathogen Anti - virulence (ALS - 4) 18 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Mechanism of Action: Staphyloxanthin of Staphylococcus aureus The above diagram summarizes the mechanism of action by Staphyloxanthin of Staphylococcus aureus: • Neutrophils kill bacteria including Staphylococcus aureus intracellularly or extracellularly via Reactive Oxygen Species “ROS - oxygen radicals released by neutrophils trigger the subsequent bacterial damage processes” 1 . • To counteract, Staphyloxanthin protects the bacteria by serving as an anti - oxidant to neutralize the ROS secreted by neutrophils 2 . Neut r ophil 19 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 1 Annu Rev Immunol. 2005;23:197 - 223; 2 mBio. 2017 Sep 5;8(5). pii: e01224 - 17
Mechanism of Action - ALS - 4 on Staphyloxathin Synthesis The description of ALS - 4 and related conclusory statements on ALS - 4 on this slide are based on Aptorum’s internal tests/experimentation and has not yet been verified by clinical trials or third party testing. The above diagram summarizes our findings about how ALS - 4 inhibits Staphyloxathin synthesis: 20 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited • ALS - 4 inhibits a key enzyme in the biosynthesis of Staphyloxanthin with an IC 50 = 20nM. • In the absence of Staphyloxanthin, the bacteria become susceptible to damage by ROS, triggering the usual series of mechanisms by neutrophils that ultimately leads bacterial cell death. DMSO control AL S - 4 200nM 100nM 50nM 25 nM 12.5nM 6 . 3 nM 3 . 1nM
ALS - 4: oral formulation treatment in an MRSA survival study The combination of ALS - 4’s anti - virulence properties together with host immune system, efficacy is still superior. The below in - vivo data includes rats infected with a lethal dose of MRSA USA300 in a bacteremia model. Survival (%) 21 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited Vehicle (N=9) ALS - 4 (10mg/kg) (N=9) 0% Time (d) • A lethal dose (10 9 CFU) of MRSA was introduced through the tail vein • ALS - 4 was administered orally 30 minutes after infection for twice a day thereafter 55 . 6 % p = 0.013 The results shown in this slide are based on Aptorum's internal (in vitro/in vivo) tests/experiments that have not been verified in clinical trials and/or third party testing
ALS - 4: oral formulation treatment in a non - lethal bacteremia model • Rats were challenged with a non - lethal dose (10 7 CFU) of MRSA through the tail vein • In order to simulate a more realistic clinical scenario, treatment was introduced 14 - days after infection, where ALS - 4 was administered orally twice a day at 10mg/kg per animal ALS - 4 (10mg/kg) (N=8) ALS - 4 is shown to greatly reduce organ bacterial count in a bacteremia animal model p=0.01 10 4.8 = 63,096 CFU/g Kidney bacterial count (CFU/g) (log 10 scale) 99.5%reduction 10 2.5 = 316 CFU/g 22 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited C o n t r ol (N=8) The results shown in this slide are based on Aptorum's internal (in vitro/in vivo) tests/experiments that have not been verified in clinical trials and/or third party testing
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 1 . Its primary function is to encapsidate the virus genome for RNA transcription, replication and packaging. It is also a key adapter molecule between virus and host processes 1 • ALS - 1, by targeting NPs, acts upstream of Neuraminidase inhibitors such as Tamiflu, which target the last stage (budding) of the viral life cycle 2 . This novel mechanism distinguishes ALS - 1 from all other currently marketed antiviral drugs 3 1. J Gen Virol. 2002 Apr;83(Pt 4):723 - 34; 2. Nat Biotechnol. 2010 Jun;28(6):600 - 5; 3. Refer to the next slide "ALS - 1: A Unique Antiviral Therapeutic Against Influenza A". ALS - 1 outperforms Tamiflu® (oseltamivir, in red) in vitro with a lower IC50 2 ALS - 1 inhibited viral growth up to 6 hours after infection, indicating antiviral activities reside on post - entry and post - nuclear events 2 This figure shows the concentration dependence of ALS - 1 in reducing the plaque - forming unit (pfu, a measure of number of infectious virus particulates) of human H1N1, H3N2 and H5N1 influenza viruses. The IC 50 for these viruses is between 0.1 - 1μM This figure shows that MDCK cells were infected and ALS - 1 (1 μM) was added before infection ( Ɛ 1 h), at the time of infection (0 h) and at 1, 2, 4, 6 and 8 hour after infection as indicated. (+) control without ALS - 1 23 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Claves Executive Summary Human Microbiota • We live in constant symbiosis with our gut bacteria, and dysbiosis can be the cause to numerous diseases 1 Claves Technology • The Claves technology is designed to physically modulate the chemical signaling of diseases - causing microbiota 2 • Highly scalable large molecule technology with over 70 potential therapeutic targets possible for development 2 • Claves therapeutics bind target chemicals with high affinity and specificity, they are non - absorbable and expected to be free from any systemic toxicity 2,3 • Multiple candidates under development for various indications 2 • CLS - 1 is the lead program in the Claves projects, intended to target metabolites secreted by the microbiota linked to obesity 2 • CLS - 1 is also shown to modulate gut microbiota population linked to obesity 2,3 • CLS - 1 achieves significant weight loss in a mouse model without affecting the gut mucosa, inflammation, and the functions of the liver and kidneys 2,3 • Non - absorbable nature of the Claves therapeutics may expedite traditional toxicological studies 2 CLS - 1: Lead Program Targeting Obesity 24 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 1. Lancet. 2003 Feb 8;361(9356):512 - 9; 2. Based on Aptorum's internal tests/experimentation and has not yet been verified by clinical trials or third party testing; 3. Data available in this presentation; 4. Current understanding of dysbiosis in disease in human and animal models, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838534/ • Contains 100s of species of microbes • Constantly producing 1000s of active metabolites • Some metabolites provides immunological and metabolic benefits • Dysbiosis (microbial imbalance) is a significant factor in disease 4
Claves Platform and CLS - 1: Value Proposition C L S - 1 • Identified specific microbiota metabolite linked to obesity • Novel therapeutic that physically modulates microbiota metabolite • Acts locally in the gut with high affinity and specificity • Non - absorbable and is expected to be free from any systemic toxicity • Significant weight loss in an animal study Claves Platform • Novel platform technology that can be customized to bind a wide variety of microbiota metabolites with high affinity and specificity • Sustainable pipeline of drug candidates for treatment of multiple indications (see next page) All conclusory statements on this slide are based on Aptorum’s internal tests/experimentation and has not yet been verified by clinical trials or third party testing. 25 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
Mechanism of Action Metabolite 1 produced by the microbiome and its link to obesity • High - fat diet in rats increased levels of metabolite 1 in the GI tract • High metabolite 1 turnover promotes obesity and metabolic syndrome • Metabolite 1 drives via a number of pathways to cause increased insulin secretion and nutrient intake • Majority of GI tract metabolite 1 produced by microbiome • CLS - 1 specifically binds to and removes metabolite 1 from the body • CLS - 1 is a macromolecule that, due to its particle size (over 20um), cannot be ab sorbed into the systemic circulation (both on its own and in combination with the metabolite 1) • The combined form passes out through the digestive system and therefore, removing metabolite 1 from the gut. All conclusory statements on this slide are based on Aptorum’s internal tests/experimentation and has not yet been verified by clinical trials or third party testing. 26 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
CLS - 1: Market Overview Recent Deals in Obesity Treatment • Boehringer Ingelheim committed up to USD 300m to work with Gubra on obesity treatments Competing Drugs • CLS - 1 is a drug candidate for obesity treatment that achieves its effect by modulating the chemical signaling of gut microbiota. There are no obesity treatment drugs on the market using similar mechanism 3 . CLS - 1: the lead program in the Claves projects, targeting obesity 27 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
CLS - 1: Efficacy in a Mouse Model CLS - 1 treatment significantly reduces body weight in mice The above data are based on Aptorum's internal tests and has not yet been verified by clinical trials or third party testing. 28 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
NLS - 2: Executive Summary NLS - 2 1 • 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 vitro and in vivo (rat animal model) • Osteoporosis is frequently associated with menopause. DOI increases the apparent bone mineral density, bone volume fraction and trabecular thickness in an in vivo rat model • DOI acts in a tissue - specific manner. Upregulation of aromatase, an enzyme involved in the production of estrogen, by DOI was found in ovary but not in other tissue • DOI does not cause toxicity in vitro based on cell viability in the MTT assay • Targeting to launch as a dietary supplement in H2 2020 Timeline 2 1. Lancet. 2003 Feb 8;361(9356):512 - 9; 2. Data available in this presentation All conclusory statements on this slide are based on Aptorum’s internal tests/experimentation and has not yet been verified by clinical trials or third party testing. 29 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited
APPENDIX
Income Statement Summary (U.S. GAAP) 1 Notes: 1. The following slide contains selected information for the Company's income statement. Please see the Company's most recently file d F orm 20 - F for the Company's complete financial statements. 2. During the year ended December 31, 2019 and 2018, the net interest expenses included USD 3.1 M and USD 2.4 M, respectively, amortization of beneficial conversion feature which are non - cash items. Year ended December 31, Year ended December 31, 2019 2018 US$ US$ Revenue 535,166 383,450 Research and development expenses (6,939,051) (3,101,432) General and administrative fees (7,373,425) (4,919,626) Legal and professional fees (3,405,705) (1,811,770) Net loss attributable to Aptorum Group Limited (18,686,762) (14,831,723) Net loss per share – basic and diluted (0.64) (0.53) Interest (expense) income, net 2 (3,699,672) (4,458,191) Depreciation and amortization (1,299,618) (682,902) 31 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited Share based compensation expenses (1,612,832) -
Selected Balance Sheet Items (U.S. GAAP) 1 Notes: 1. The following slide contains selected information for the Company's balance sheets. Please see the Company's most recently filed form 20 - F for the Company's complete financial statements. 2. Current assets less current liabilities. 3. Since September 2019, Aptorum Group has access to over USD15m in working capital from shareholder support December 31, 2019 32 For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited December 31, 2018 US$ US$ Cash, restricted cash and marketable securities 6,356,284 27,121,576 Total current assets 8,032,881 28,722,941 Property, plant and equipment, net 7,093,035 4,260,602 Total assets 23 , 954 , 21 8 45 , 074 , 64 0 Convertible debts - (10,107,306) Warrant liabilities - ( 7 5 3 , 1 1 8) Total current liabilities (2,674,675) (12,184,865) Total liabilities (9,102,466) (12,328,738) Total equity attributable to the shareholders of Aptorum Group Limited 16,361,208 33,114,435 Working Capital 2,3 5,358,206 16,538,076
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