Exhibit 99.4
Facilitating Life Science Innovations to Serve Unmet Medical Needs CORPORATE PRESENTATION NASDAQ GLOBAL MARKET: APM
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 2 Disclaimer 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 stateme nts contained herein that are not statements of historical fact may be deemed to be forward - looking statements. In some cases, you can identify forwa rd - looking statements by terms such as “may,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “target,” “projects,” “c ont emplates,” “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 comm ercialization 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 doc ument 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 add itional products for additional consumer segments, development results, the company’s anticipated growth strategies, anticipated trends and challe nge s 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.
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 3 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 and cross - listed on Euronext Paris (ticker symbol: APM) on July 24, 2020 • Company’s principal office based in London, United Kingdom • Core development site based in 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
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 1 Directors, Management and Significant Employees • 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 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 and Ex Head of TVM Asia MR. CHARLES BATHURST Founder of Summerhill Advisors Limited • Over 20 years of experience in medical field; • Chairman of the Board of Directors of Todos Medical; • Former Head of Clinical Development and Medical Affairs at Juniper Pharmaceuticals; • MBA, George Washington University; M.D., Ohio State University DR. HERMAN WEISS CEO of Claves Life Sciences Senior Medical Advisor of Aptorum Group
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 2 Aptorum Team • Professor of Surgery, School of Medicine, University of Chicago; • Former A sso . Professor at Johns Hopkins University; • M.D., Johns Hopkins University School of Medicine DR. NISHANT AGRAWAL Senior Clinical Advisor Consultants and Advisors to Aptorum Group and Subsidiaries 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 • Asso . Professor, School of Pharmacy, The Chinese University of Hong Kong; • Research Officer, Faculty of Medicine, The University of Hong Kong; • Ph.D. in Neurosciences, UC San Diego DR. FRANCIS SZELE Senior Scientific Advisor • Assistant professor of Pediatrics (Hematology/Oncology) at the Stanford University Medical Center; • Completed residency training in pediatrics and fellowship training in pediatric hematology - oncology; • Board certified in pediatrics and pediatric hematology - oncology; • M.D., Harvard Medical School 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 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 • 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. DR. ROBBIE MAJZNER Advisor
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 6 Current progress of leading pipeline programs and discovery NDA NDA 1. Refers to the drug’s existing Phase I/II safety data previously conducted by a third party. Does not refer to clinical tri als conducted by Aptorum 2. Subject to FDA’s approval
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 7 Current progress of leading pipeline programs and discovery
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 8 4."35 "$5 Π %SVH%JTDPWFSZ1MBUGPSN0SQIBO%JTFBTF'PDVTBOE4FMFDUJPO 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 priority Patient population definition: • US: <200,000 patients • EU: <5 in 10,000 • Japan: <50,000 patients • China: defined list of 121 rare diseases 7000+ Orphan Diseases 4."35 "$5 ́ )JHI1SJPSJUZ 0SQIBO%JTFBTFT
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome l%QR[TKIJV #RVQTWO)TQWR.KOKVGF 9 4."35 "$5 Π 1JQFMJOF8PSLýPX 2 ,600 FDA - approved small molecule drugs • Life threatening disease • Lack of effective treatment • Large market size New drug indication • Computational mining from literature • Up to 5 disease drug targets selected &TWIVCTIGVUGNGEVKQP 2 • Cell line model • IC 50 • Combo treatment standard therapy In vitro validation 5 9GVNCD Computational ‡ #PKOCNOQFGN ‡ ,QYLYR GHHKECE[ In vivo validation • Indication patent • Reformulation • Combination patent • Dosage patent IP protection 7 ‡ 75( D HKNKPI ‡ +P JQWUGFGXGNQROGPVQTQWV NKEGPUKPIYKVJEQ FGXGNQROGPV RCTVPGTU Development / out - licensing In silico generated hits
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 10 4"$5 OFVSPCMBTUPNB NBSLFUPWFSWJFX • ~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 4"$5 UBSHFUTOFVSPCMBTUPNB BDBODFSUIBUEFWFMPQTGSPNOFSWFDFMMT 1. Pediatr Rev. 2018 Feb;39(2):57 - 67; 2. “Neuroblastoma Market Global Industry Perspective, Comprehensive Analysis, Size, Share, Growth, T rends, 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 1SFWBMFODF 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 All conclusory statements on this slide are based on Aptorum’s internal tests/experimentation and has not yet been verified b y c linical trials or third party testing. 1 64 CO 3 . 7 Most common type of solid tumor in children 1 Value of the global neuroblastoma treatment market in 2017 2 CAGR global neuroblastoma treatment market (2019 - 2023) 2 DĂƌŬĞƚ^ŝnjĞ
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 / ϱϬ ђD &Žƌ/DZ Ͳ ϯϮ IC 50 [µM] For SK - N - BE(2) IC 50 [µM] For SK - N - SH IC 50 [µM] For SH - SY5Y SACT - 1 2.97 3.37 2.75 3.12 $POUSPMUSFBUNFOUPOOFVSPCMBTUPNB DFMMT SACT - 1 treatment on neuroblastoma cells
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 ϭ͘ϭϭ 3.33 10 0.2 Ϭ͘ϰ Standard Tx ( μ M) Excess over Bliss SACT - 1 ( μ M) EĞƵƌŽďůĂƐƚŽŵĂĐĞůůůŝŶĞη ϭ 10 13 5 0 11 9 2 - 7 0.37 1.11 3.33 ϭϬ 0.2 0.4 Standard Tx ( μ M) džĐĞƐƐŽǀĞƌůŝƐƐ SACT - 1 ( μ M) Neuroblastoma cell line #2 Synergistic ŶƚĂŐŽŶŝƐƚŝĐ Standard Tx ( μ M) SACT - 1 ( μ M) Synergism "OUBHPOJTN 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
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: Combination study with standard chemotherapy in vivo model ** Unpaired Student’s T - test, p<0.01, n=8 (based on data observed over initial 22 day period of the study, with SOC applied from day 1 to day 15 and SACT - 1 applied from day 1 to day 21) SACT - 1 when combined with standard of care chemotherapy showed a statistically significant reduction in tumour volume in a xenograft mouse model. 5IFSFTVMUTTIPXOJOUIJTTMJEFBSFCBTFEPO "QUPSVNhT JOUFSOBM JOWJUSPJOWJWP UFTUTFYQFSJNFOUTUIBUIBWFOPUCFFOWFSJGJFEJODMJOJDBMUSJBMTBOEPSUIJSEQBSUZUFTUJOH
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 14 SACT - 1: safety & tolerability ‡ %JEOPUTIPXHFOPUPYJDQPUFOUJBMFWFO BUUIFIJHIFTUGFBTJCMFDPODFOUSBUJPO EPTF JOWJUSP BOE JOWJWP ‡ *OBQIBTF**CTUVEZPWFS ZFBST BMM 4"$5 EPTFTXFSFTBGFBOEXFMM UPMFSBUFE ‡ /PEPTFSFMBUJPOTIJQCFUXFFO317BOE BEWFSTFFWFOUT "& Well - established Safety profile based on a FDA approved product Ref: doi : 10.1089/AID.2011.0050 RPV 25mg/day (N=93) 75mg/day (N=95) 150mg/day (N=91) Median treatment duration, weeks 101 100 100 Adverse events (AE) ŶLJŐƌĂĚĞ Ϯ Ͳ ϰ ĂƚůĞĂƐƚƉŽƐƐŝďůLJƌĞůĂƚĞĚƚŽZWs 20% 20% 21% AEs leading to discontinuation 9% 12% 14% Any serious AE 13% 14% 10% Deaths 0% 2% 0% • 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 '%"BQQSPWFEQIBSNBDPLJOFUJDTQSPåMF
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 15 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 ‡ "VOJRVFBOUJWJSBMUIFSBQFVUJDBHBJOTU*OGMVFO[B"UIBUIBTBNPSFVQTUSFBNUBSHFUUIBO5BNJGMV ¥ XIJDIJTTIPXOUP CFNPSFFGGFDUJWFJOWJUSP ‡ 7JSBMSFTJTUBODFUP5BNJGMVBOEPUIFSOFVSBNJOJEBTFJOIJCJUPSTIBTSJTFOSBQJEMZJOSFDFOUZFBST ‡ "-4 IBTBEJTUJODUNFDIBOJTNPGBDUJPODPNQBSFEXJUI5BNJGMV ¥ BOE9PGMV[B 5. ALS - 1 ALS - 2/ALS - 3 • 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
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 16 ALS - 4: Market Overview ‡ *O .FSDLhTBDRVJTJUJPOPG$VCJTU1IBSNBDFVUJDBMT BMBSHFEFWFMPQFSPGBOUJCJPUJDT GPS64% CO ‡ *O 3PJWBOUhT MJDFOTJOHPG*OUSPOhT1IBTF**BTTFUGPS64% NJOVQGSPOUBOENJMFTUPOFQBZNFOUT 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, Siz e, 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 - 300753307.html Third - party infectious disease drugs or company - related mergers and acquisitions 30 % US$ 2 . 9 bn 3 . 2 % 濩濴濿瀈濸澳瀂濹澳瀇濻濸澳濺濿瀂濵濴濿澳 濠濥濦濔澳濷瀅瀈濺瀆澳瀀濴瀅濾濸瀇澳 濼瀁澳 濅濃濄濉 濅 CAGR global MRSA drugs market (2017 - 2025) 2 Market Size Mortality rate of patients with S. aureus bacteremia 1
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 17 Market Approved Drugs for MRSA Infections 'SFRVFOUMZQSFTDSJCFEBOUJCJPUJDTGPS.34"JOGFDUJPOT Product (Company) Antibiotic Class Indication(s) RoA Dose Cost of Treatment (duration) Notes Vancomycin (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 Daptomycin (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 Linezolid (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 Ceftaroline 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 Tigecycline (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 ( Theravance 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): 12 6 – 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 treatme nt 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 Infe ct. 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.
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 18 ALS - 4: Addressing the Shortfall of 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 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 I nfect 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 D ec;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 S erious 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 sĂŶĐŽŵLJĐŝŶ 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
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 Infe ct 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 %JSFDUFEBHBJOTUQBUIPHFO Anti - virulence (ALS - 4)
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 20 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 . Neutrophil "OOV3FW*NNVOPM N#JP 4FQ QJJ F
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 21 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 : • 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 "-4 200nM 100nM 50nM 25nM 12.5nM 6.3nM 3.1nM
(QTKNNWUVTCVKXGRWTRQUGUQPN[6JGTGKUPQIWCTCPVGGQHCP[RTQLGEVDGKPIEQORNGVGFQTJCXKPICURGEKHKEQWVEQOG © Copyright 2020 Aptorum Group Limited 22 ALS - 4: oral formulation treatment in an MRSA survival study • 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 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 (%) Time (d) 7FIJDMF / "-4 NHLH / 55.6% 0% 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 verif ied in clinical trials and/or third party testing
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 23 "-4 PSBMGPSNVMBUJPOUSFBUNFOUJOBOPO MFUIBM CBDUFSFNJB NPEFM • 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 is shown to greatly reduce organ bacterial count in a bacteremia animal model Kidney bacterial count (CFU/g) (log 10 scale) 10 4.8 = 63,096 CFU/g ALS - 4 (10mg/kg) (N=8) 10 2.5 = 316 CFU/g p=0.01 SFEVDUJPO Control (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
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 24 ALS - 4: Oral administration in a MRSA non - lethal bacteraemia mouse model ALS - 4 ( Compound IM032) with increasing dose range shows a statistically significant reduction in bacteria count across major organs relative to vancomycin as a control. 5IFSFTVMUTTIPXOJOUIJTTMJEFBSFCBTFEPO "QUPSVNhT JOUFSOBM JOWJUSPJOWJWP UFTUTFYQFSJNFOUTUIBUIBWFOPUCFFOWFSJGJFEJODMJOJDBMUSJBMTBOEPSUIJSEQBSUZUFTUJOH Kidney CFU count L o g ( C F U / g ) K i d n e y I n i t i a l c o u n t , 1 h r V e h i c l e , P O , B I D x 7 d V a n c o m y c i n , 3 m g / k g , I V , Q D x 7 d I M 0 3 2 , 3 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 3 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 m g / k g , P O , B I D x 7 d I M 0 3 2 , 0 . 3 m g / k g , P O , B I D x 7 d 0 2 4 6 * Lung CFU count L o g ( C F U / g ) L u n g I n i t i a l c o u n t , 1 h r V e h i c l e , P O , B I D x 7 d V a n c o m y c i n , 3 m g / k g , I V , Q D x 7 d I M 0 3 2 , 3 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 3 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 m g / k g , P O , B I D x 7 d I M 0 3 2 , 0 . 3 m g / k g , P O , B I D x 7 d 0 1 2 3 4 5 *** *** * * Liver CFU count L o g ( C F U / g ) L i v e r I n i t i a l c o u n t , 1 h r V e h i c l e , P O , B I D x 7 d V a n c o m y c i n , 3 m g / k g , I V , Q D x 7 d I M 0 3 2 , 3 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 3 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 m g / k g , P O , B I D x 7 d I M 0 3 2 , 0 . 3 m g / k g , P O , B I D x 7 d 0 2 4 6 * * ** Spleen CFU count L o g ( C F U / g ) S p l e e n I n i t i a l c o u n t , 1 h r V e h i c l e , P O , B I D x 7 d V a n c o m y c i n , 3 m g / k g , I V , Q D x 7 d I M 0 3 2 , 3 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 0 m g / k g , P O , B I D x 7 d I M 0 3 2 , 3 m g / k g , P O , B I D x 7 d I M 0 3 2 , 1 m g / k g , P O , B I D x 7 d I M 0 3 2 , 0 . 3 m g / k g , P O , B I D x 7 d 0 2 4 6 ** *** ***
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 25 ALS - 4: Oral administration in a MRSA mouse skin wound infection model 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 *unpaired t - test: p<0.05 ALS - 4 (Compound IM032) shows a statistically significant improvement in skin wound closure / healing. ĂLJ Ϭ ĂLJ ϳ Ϯ йDƵƉŝƌŽĐŝŶdŽƉŝĐĂů/dž ϳ ĂLJƐ Day 0 Day 7 Linezolid 100mg/kg PO BID x 7 Days Day 0 Day 7 ALS - 4 30mg/kg PO BID x 7 Days
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 26 ALS - 1: Targeting a Novel Druggable Target for Influenza A • 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 "-4 JOIJCJUTJOýVFO[B"OVDMFPQSPUFJO /1 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 ( - 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
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 • We live in constant symbiosis with our gut bacteria, and dysbiosis can be the cause to numerous diseases 1 Human Microbiota • 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 Claves Technology • 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 -BODFU 'FC #BTFEPO"QUPSVNhTJOUFSOBMUFTUTFYQFSJNFOUBUJPOBOEIBTOPUZFUCFFOWFSJGJFECZDMJOJDBMUSJBMTPSUIJSEQBSUZUFTUJOH %BUBBWBJMBCMFJOUIJTQSFTFOUBUJPO $VSSFOUVOEFSTUBOEJOH PGEZTCJPTJTJOEJTFBTFJOIVNBOBOEBOJNBMNPEFMT IUUQTXXXODCJOMNOJIHPWQNDBSUJDMFT1.$ • 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
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 28 Claves Platform and CLS - 1: Value Proposition CLS - 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) "MMDPODMVTPSZTUBUFNFOUTPOUIJTTMJEFBSFCBTFEPO"QUPSVN TJOUFSOBMUFTUTFYQFSJNFOUBUJPOBOEIBTOPUZFUCFFOWFSJGJFECZDMJOJDBMUSJBMTPSUIJSEQBSUZUFTUJOH Microbiota - associated therapeutic targets for various diseases Claves platform Sustainable therapeutic pipeline POSSIBLE INDIC A TIONS SYSTEMIC DISEASES DIGESTIVE DISEASES Obesity Renal failure C. difficile infection Diabetes Depression Colorectal cancer Fatty liver Parkinsonism Inflammatory bowel disease Cardiovascular diseases Autistic spectrum disorder Irritable bowel syndrome
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 29 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 b y c linical trials or third party testing. Neurodegenerative Diseases C a r di o v ascular Diseases M etabolic Diseases I n t estinal Epithelium Metabolites from Gut Microbiota Gut M ic r obiota CLS Drug C andid a t e M ic r obiome Metabolite C ompl e x
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 30 CLS - 1: Market Overview • Boehringer Ingelheim committed up to USD 300m to work with Gubra on obesity treatments Recent Deals in Obesity Treatment • 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 . Competing Drugs CLS - 1: the lead program in the Claves projects, targeting obesity 13 % US$ 6.1 bn 16 . 7 % Value of the global obesity treatment market in 2018 2 CAGR global obesity treatment market (2018 - 2026) 2 Market Size o f the world’s adult population were obese in 2016 1
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 31 CLS - 1: Efficacy in a Mouse Model The above data are based on Aptorum's internal tests and has not yet been verified by clinical trials or third party testing. Significant weight loss within 2 weeks Weight (gram) Days 40 35 30 25 0 60 40 20 Group 1: High - fat diet + CLS - 1 Group 2: High - fat diet + control High - fat diet only Weight Change (gram) 6 4 2 0 - 2 - 4 Group 3 Group 2 Group 1 CLS - 1 given to the animals CLS - 1 treatment significantly reduces body weight in mice
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 32 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 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 1. Lancet. 2003 Feb 8;361(9356):512 - 9; 2. Data available in this presentation NLS - 2 1 Timeline 2 All conclusory statements on this slide are based on Aptorum’s internal tests/experimentation and has not yet been verified b y c linical trials or third party testing.
APPENDIX
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 34 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 filed Form 6 - K for the Company’s interim financial results and Form 20 - F for the Company's complete financial statements . 2 . During the six months period ended June 30 , 2019 , and years ended December 31 , 2019 and 2018 , the net interest expenses included USD 3 . 1 M, USD 3 . 1 M and USD 2 . 4 M, respectively, amortization of beneficial conversion feature which are non - cash items . No such amortization of beneficial conversion feature was incurred during the six months ended June 30 , 2020 . Six months ended June 30, 2020 Six months ended June 30, 2019 Year ended December 31, 2019 Year ended December 31, 2018 US$ US$ US$ US$ (Unaudited) (Unaudited) Revenue 327,273 239,792 535,166 383,450 Research and development expenses (4,315,033) (2,714,217) (6,939,051) (3,101,432) General and administrative fees (2,076,634) (3,232,916) (7,373,425) (4,919,626) Legal and professional fees (1,540,304) (2,008,774) (3,405,705) (1,811,770) Net loss attributable to Aptorum Group Limited (6,204,565) (9,088,471) (18,686,762) (14,831,723) Net loss per share – basic and diluted (0.21) (0.31) (0.64) (0.53) Interest expense, net 2 (144,226) (3,678,566) (3,699,672) (4,458,191) Depreciation and amortization (702,633) (585,701) (1,299,618) (682,902) Share based compensation expenses (584,094) (593,806) (1,612,832) -
For illustrative purposes only. There is no guarantee of any project being completed or having a specific outcome © Copyright 2020 Aptorum Group Limited 35 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 fi led Form 6 - K for the Company’s interim financial results and Form 20 - F for the Company's complete financial statements.. 2. Current assets less current liabilities. 3. As at 30 June 2020, Aptorum Group also has undrawn credit facility of c. USD13m available as additional working capital. June 30, 2020 December 31, 2019 December 31, 2018 US$ US$ US$ ( Unaudited ) Cash, restricted cash and marketable securities 4,426,543 6,356,284 27,121,576 Total current assets 6,128,019 8,032,881 28,722,941 Property, plant and equipment, net 6,140,602 7,093,035 4,260,602 Total assets 23,309,075 23,954,218 45,074,640 Convertible debts - - (10,107,306) Warrant liabilities - - (753,118) Total current liabilities (3,080,408) (2,674,675) (12,184,865) Total liabilities (5,786,690) (9,102,466) (12,328,738) Total equity attributable to the shareholders of Aptorum Group Limited 19,837,917 16,361,208 33,114,435 Working Capital 2,3 3,137,611 5,358,206 16,538,076
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