SEC Filing | Aptorum Group Limited

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 6-K

REPORT OF FOREIGN PRIVATE ISSUER

PURSUANT TO RULE 13a-16 OR 15d-16

UNDER THE SECURITIES EXCHANGE ACT OF 1934

For the month of February 2020

Commission File Number: 001-38764

APTORUM GROUP LIMITED

17^thFloor, Guangdong Investment Tower

148 Connaught Road Central

Hong Kong

(Address of principal executive offices)

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F: Form 20-F ☒ Form 40-F ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1): ☐

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ☐

On February 10, 2020, Aptorum Group Limited (the “Company”) issued two press releases regarding certain of its lead projects and drug candidates under development. Copies of the press releases are attached hereto as Exhibit 99.1 and Exhibit 99.2. We are also filing this report to disclose the revised power point presentation the Company will use during corporate presentations; such power point presentation is incorporated herein by reference.

Neither this report, the press releases, nor the power point presentation attached as exhibits hereto constitute an offer to sell, or the solicitation of an offer to buy our securities, nor shall there be any sale of our securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

The information in this Form 6-K, including the exhibits shall not be deemed to be “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and shall not be incorporated by reference into any filing under the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such filing.

This Form 6-K is hereby incorporated by reference into the registration statements of the Company on Form S-8 (Registration Number 333-232591) and Form F-3 (Registration Number 333-235819) and into each prospectus outstanding under the foregoing registration statements, to the extent not superseded by documents or reports subsequently filed or furnished by the Company under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended.

EXHIBIT INDEX

Exhibit No.		Description
99.1		Press Release
99.2		Press Release
99.3		Power Point Presentation

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

	Aptorum Group Limited

Date: February 10, 2020	By:	/s/ Sabrina Khan
		Name: Sabrina Khan
		Title: Chief Financial Officer

EXHIBIT INDEX

Exhibit No.		Description
99.1		Press Release
99.2		Press Release
99.3		Power Point Presentation

Exhibit 99.1

NASDAQ: APM

Aptorum Group Announces Significant Progress of Repurposed Drug Candidate, SACT-1 for Neuroblastoma Targeting IND Submission in H2 2020

NEW YORK -- (BUSINESS WIRE) – Aptorum Group Limited (Nasdaq: APM) (“Aptorum Group”), a biopharmaceutical company focused on the development of novel therapeutics to address global unmet medical needs, announces positive data and development in relation to its repurposed drug candidate, SACT-1, for the treatment of neuroblastoma, a rare type of childhood cancer that develops in infants and young children. Subject to completion of current validation studies, Aptorum Group plans to leverage the 505(b)(2) pathway and submit an IND submission with the FDA for SACT-1 in H2 2020.¹

SACT-1 is the first repurposed drug candidate to be developed under the Smart-ACT™ drug discovery platform, which employs a systematic approach to identify, repurpose and develop existing approved drugs against a currently identified universe of 7000+ (and increasing) orphan diseases.²

Through this platform, Aptorum Group intends to accelerate and fast track repurposed drug candidates, which usually have well established human safety and toxicity profiles and data, through the development and clinical phases in order to address the rapidly growing market of orphan diseases. Aptorum Group aims to screen a number of orphan disease areas including, but not limited to, oncology, autoimmune, metabolic and genetic diseases.

Through the Smart-ACT^™ platform, Aptorum has successfully identified potential efficacy for and develops SACT-1 for the treatment of neuroblastoma, being an entirely new therapeutic area from its approved indication. In our recent studies, SACT-1 has been shown to be effective against numerous neuroblastoma cell lines, of which 2 are MYCN-amplified cells, which represent the high-risk neuroblastoma patient group. In addition, by using a combination index as a quantitative measure of the extent of drug interaction, Aptorum Group has seen a high and robust synergism between SACT-1 and traditional chemotherapy in vitro, indicating a potential efficacy enhancement/dose reduction of the chemotherapy. In addition, in our recent study, the maximum tolerable dose of SACT-1 in a rodent model was determined to be higher than 400mg/kg. Compared with the MTD of standard chemotherapy such as paclitaxel (20-30mg/kg)³ and cisplatin (6mg/kg) ⁴, the safety profile of SACT-1 appears to be very impressive.

The reformulation of SACT-1 is a pediatric formulation to better address the needs of neuroblastoma patients who are exclusively children younger than 5. Based on our internal observations of pre-existing information from approved products,⁵ SACT-1 also exhibits a well-established safety profile: at 150mg/day, the death rate was 0% in prior clinical studies with no dosage related adverse events.

¹ If the FDA deems the 505(b)(2) pathway as an acceptable route for approval of SACT-1, the Company will be able to leverage existing clinical and nonclinical data in conjunction with sponsor-initiated studies to accelerate development and approval of SACT-1.

² See https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases

³ Clin Cancer Res. 5(11):3632-8.

⁴ BMC Cancer 17: 684 (2017).

⁵ Subject to FDA's approval and on a case-by-case basis, a 505(b)(2) application can rely in part on existing information from approved products (such as the FDA's previous findings on safety and efficacy) or products in literature (such as data available). However, typically speaking, the applicant is nonetheless required to carry out a Phase 1 bridging study to compare the Reference Listed Drug and reference the established safety and efficacy information.

About neuroblastoma

Neuroblastoma is a rare form of cancer, and classified as an orphan disease, that forms in certain types of nerve tissue and most frequently in the adrenal glands as well as spine, chest, abdomen or neck, predominantly in children, especially for those aged 5 years and below. For the high-risk group, which is close to 20%⁶ of total new patient population per year, the 5-year survival rate of this condition is around 40-50% as observed by the American Cancer Society⁷. The current high drug treatment cost for high risk patients can average USD200,000 per regimen (all 6 cycles)⁸. In addition, most pediatric patients often do not tolerate or survive the relevant chemotherapy stage which we believe, subject to further clinical studies, may be positively addressed by the SACT-1 candidate due to the potential synergistic effects when applied with standard chemotherapy as described above.

For further general presentation, please visit:

http://ir.aptorumgroup.com/static-files/bcf77574-7bd6-4b9d-8110-d53837238f16

For further technical presentation, please visit:

http://ir.aptorumgroup.com/static-files/66346f79-7a03-474a-89be-0eaafaa00d9d

About Aptorum Group Limited

Aptorum Group Limited (Nasdaq: APM) is a pharmaceutical company dedicated to developing and commercializing novel therapeutics to tackle unmet medical needs. Aptorum Group is pursuing therapeutic projects in orphan diseases, infectious diseases, metabolic diseases and other disease areas.

For more information about Aptorum Group, please visit www.aptorumgroup.com.

About Smart Pharma Group

Smart Pharma Group is wholly owned by Aptorum Group Limited. Smart Pharma Group focuses on systematically identifying and repurposing existing approved drugs for the treatment of a large array of orphan diseases. Smart Pharma Group conducts both computational based screening and clinical validations in advancing the development of its repurposed candidates.

Disclaimer and Forward-Looking Statements

This press release 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 and trials, 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 press release 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 press release as a result of new information, future events or otherwise.

Contact

Investors:

Tel: +852 2117 6611

Email: investor.relations@aptorumgroup.com

Media:

Tel: + 852 2117 6611

Email: info@aptorumgroup.com

⁶ Annu Rev Med. 2015; 66: 49–63.

⁷ https://www.cancer.org/cancer/neuroblastoma/detection-diagnosis-staging/survival-rates.html

⁸ https://www.cadth.ca/sites/default/files/pcodr/Reviews2019/10154DinutuximabNeuroblastoma_fnEGR_NOREDACT-ABBREV_Post_26Mar2019_final.pdf

Exhibit 99.2

NASDAQ: APM

Aptorum Group Announces Further Positive Data For Its ALS-4 Small Molecule Anti-virulence (Non-bactericidal) Drug Candidate For The Treatment of Infections Caused By Staphylococcus Aureus and On Track Targeted For IND Submission in H2 2020

NEW YORK -- (BUSINESS WIRE) – Aptorum Group Limited (NASDAQ: APM) (“Aptorum Group”), a biopharmaceutical company focused on the development of novel therapeutics to address global unmet medical needs, announces further positive data from its current investigational new drug (IND)-enabling studies for ALS-4, a small drug molecule candidate indicated for the treatment of infections caused by Staphylococcus aureus (or “S. aureus”), including methicillin-resistant Staphylococcus aureus (MRSA, one of the “super-bugs”), based on a novel anti-virulence non-bactericidal approach. Subject to completion of the current studies, Aptorum Group targets to submit IND for ALS-4 in second half of 2020 and commence a phase 1 trial in North America.

ALS-4 is a small molecule which inhibits dehydrosqualene desaturase of S. aureus (incl. MRSA), an enzyme that is critically involved in the biosynthesis of staphyloxanthin, a commonly visible “golden pigment” covering the bacteria. Staphyloxanthin is believed to be primarily responsible for the bacteria’s defense mechanism against the attack from reactive oxygen species (ROS) deployed by phagocytic cells and neutrophils.¹

Through inhibiting the production of staphyloxanthin, we believe that ALS-4 renders S. aureus highly susceptible to the host’s immune defense (see below for in vivo data and experimental outline). This novel mechanism is significantly different from the bactericidal approach found in currently marketed antibiotics used to treat S. aureus, which are experiencing increasing drug resistance issues². Specifically, MRSA infections in humans typically exhibit high rates of morbidity and mortality and can cause metastatic or complicated infections such as infective endocarditis or sepsis, with relapse and hospital readmission after S. aureus bacteremia common and costly³.

Based on our testing in a rat bacteremia survival model, a lethal (10⁹ CFU) dose of MRSA (USA300-LAC) was introduced through the tail vein. ALS-4 was administered orally at 10mg/kg per animal 30 minutes after the infection for twice a day thereafter (N=9). A control untreated group was given a sterile vehicle solution (N=9). Survival was monitored for 7 days. 0 out of 9 animals (0%) in the control untreated group survived past day 4, in contrast, 5 out of 9 animals (56%) treated with ALS-4 survived past day 7, which is determined to be statistically significant compared with the control group (p=0.013).

¹mBio 2017 8(5): e01224-17

² Microbiol Spectr. 2019 Mar;7(2)

³ Clin Infect Dis. 2019 Nov 27;69(12):2112-2118

In addition we conducted a study in a non-lethal rat bacteremia infection model. The animals were challenged with a non-lethal (10⁷ CFU) dose of MRSA (USA300-LAC) through the tail vein. In order to simulate a more realistic clinical scenario, treatment was introduced 14-days after the model induction, where ALS-4 was administered orally twice a day at 10mg/kg per animal (N=8). A control untreated group was given a sterile vehicle solution (N=8). After 7 days of ALS-4 treatment, the kidneys were collected and the bacterial titers were measured. Remarkably, ALS-4 reduced the organ bacterial load by 99.5%, from 63,096±18 CFU/g in the control group to 316±49 CFU/g in the ALS-4 treated group, which is determined to be statistically significant (p=0.01).

Last but not least, ALS-4 has successfully inhibited staphyloxanthin production in 11 strains of S. aureus. These include 5 strains of Methicillin-sensitive S. aureus (MSSA): SH1000, HG003, USA300-JE2, Newman, and ATCC29213 with an IC₅₀ of 70.5±6nM, 54.4±4nM, 37.7±4nM, 23.7±1nM, and 30.02±5nM respectively; 5 strains of Methicillin-resistant S. aureus (MRSA): USA300, USA300-3, USA300-LAC, ST239III, and COL, with an IC₅₀ of 30.8±5nM, 42.8±6nM, 43.6±5nM, 16.3±8nM, and 0.9±1nM respectively; and 1 strain of vancomycin-intermediate S. aureus (VISA), Mu3 with an IC₅₀ of 2.6±1nM.

Based on our testing, we believe ALS-4 increases the susceptibility of S. aureus including MRSA to oxidative damage by inhibiting production of staphyloxanthin. In a hydrogen peroxide killing assay, after the addition of 1.5% H₂O₂, ALS-4 demonstrated an additional reduction of bacterial CFU by 93.5%, from 61,600±6437 CFU/ml in the untreated group to 4,000±230 CFU/ml in the ALS-4 treated group, which is determined to be statistically significant (p=0.003).

With respect to the study carried out to investigate the capability of ALS-4 to induce antibiotic resistance in S. aureus after prolonged exposure, USA300-LAC was cultured in 3 different conditions for 10 days. For the treatment group 1 µM of ALS-4 was added; for the positive control group 0.12 µg/mL of clindamycin and 16 µg/mL of erythromycin was added from day 1 to day 4, after which clindamycin was withdrawn. For the negative control group, dimethyl sulfoxide (DMSO) was added. On day 11, the bacteria were harvested and then cultured for 16 hr for the determination of the MIC of clindamycin. The prolonged exposure to ALS-4 or DMSO does not affect the MIC value of clindamycin (0.12 µg/mL); while the prolonged exposure to clindamycin + erythromycin triggers antibiotics resistance rapidly with the MIC increased from 0.12 µg/mL to greater than 5 µg/mL.

Based on our study, we believe ALS-4 is unlikely to be prone to drug resistance since it is non-bactericidal. Growth inhibition studies were performed on different strains of S. aureus and other bacteria, including 3 strains of MSSA (ATCC29212, SH1000 and HG003), 1 strain of MRSA (USA300), 1 strain of VISA (ATCC700698 Mu3), as well as 6 different bacteria (E. coli, A. baumannii, S. cerevisiae, B. subtilis, E. faecalis, and K. pneumoniae). In all of the tested strains of bacteria, no growth inhibition effect was observed at the highest tested concentration of ALS-4 (250uM). Therefore ALS-4 does not appear to have any direct bacteriostatic or bactericidal activity against many species of bacteria, thus greatly reducing the selection pressure for drug resistance to emerge.

We also assessed the potential impact on the efficacy of vancomycin, the mainstay of treatment for infections caused by MRSA, when used in conjunction with ALS-4. 8 different strains of S. aureus (USA300 FPR3757, USA300-3, USA300-LAC, USA300-JE2, Mu3, HG003, ATCC29213 and clinical isolate ST239III) were used in this study. Our data showed that no effect on the MIC of vancomycin was observed when the concentration of ALS-4 was below 25 mM. Therefore, we believe that ALS-4 does not interfere with the action of vancomycin.

In addition, compared with the current mainstay of treatment for S. aureus infections such as vancomycin or daptomycin which is typically administered in an IV injectable form (with the exception of an oral form vancomycin specifically for treatment of Clostridium difficile diarrhea and staphylococcal enterocolitis only), an oral active agent enables wider market penetration targeting both outpatient as well as potential prophylactic markets.

GLP Toxicity Data

ALS-4 is currently undergoing IND-enabling studies and has so far shown positive safety profiles. As elucidated in our previous press release dated September 9, 2019, ALS-4 did not show any mutagenicity in the in vitro Ames tests. Our currently generated in vitro micronucleus test results also showed that ALS-4 is not genotoxic, indicating the non-mutagenic nature of the drug. Furthermore, the results of the in vitro hERG assay study predicts a low risk of ALS-4 causing cardiac QT prolongation.