Financial Performance and Revenue Generation - The company has not generated any revenue from product sales and may never become profitable without additional financing[45] - The company has not generated any revenue from drug candidates and does not foresee generating revenue in the near future[52] - The company anticipates that existing cash will likely allow for the completion of preclinical development for at least one Lead Project, but full clinical development will require additional funding[92] - The company may not achieve timely regulatory approval for its drug candidates, which could limit its ability to generate sufficient revenues and cash flows[125] Drug Development and Clinical Trials - AML Clinic commenced operations in June 2018 and is expected to be the principal source of revenue, but it may not be sufficient to support operations and R&D[51] - The average cost of launching a new drug is estimated to approach $2.6 billion and can take around 12 years to reach the market[59] - Clinical trials are lengthy and expensive, with potential failures at any stage, impacting the company's ability to advance drug candidates[71] - The company has obtained CTA/FDA approval to initiate clinical trials for Lead Projects, but patient enrollment challenges could delay these trials[68] - The company may need to conduct additional clinical trials if initial trials do not meet primary endpoints, leading to increased costs and delays[73] - Delays in clinical trials could harm the commercial prospects of drug candidates and increase costs, jeopardizing the ability to generate product sales revenues[97] Regulatory Challenges and Compliance - Regulatory approval processes are lengthy and unpredictable, with no assurance that any drug candidates will receive approval[84] - Compliance with current Good Clinical Practices (cGCP) is essential, and failure to comply could render clinical data unreliable[76] - The company may face additional post-marketing testing requirements or restrictions on drug distribution if regulatory authorities impose such conditions[89] - Compliance with FDA's Current Good Manufacturing Practices (cGMP) is mandatory, and failure to comply could result in enforcement actions that impair marketing capabilities[116] - The FDA's policies may change, potentially delaying regulatory approval of drug candidates or imposing stricter product labeling and post-marketing testing requirements[198] Intellectual Property and Patent Risks - The company relies on a significant portion of its intellectual property portfolio, which includes pending patent applications that may not be granted, potentially affecting its market position[126] - The company’s patent rights may be challenged, and even if patents are granted, they may not provide meaningful protection against competitors[131] - The company may face lawsuits to protect its intellectual property (IP), which could be expensive and time-consuming[147] - The company is at risk of losing patent protection if it fails to defend against claims of invalidity or unenforceability in court[149] - Changes in U.S. patent law could diminish the value of the company's patents, impacting its ability to protect its drug and diagnostics technology candidates[166] Competition and Market Acceptance - The company may face challenges in achieving market acceptance for its drug candidates as viable treatment options[47] - The company faces significant competition from other pharmaceutical companies with greater financial resources and expertise in research and development, which may hinder market acceptance of its drug candidates[119] - Even with regulatory approval, achieving market acceptance necessary for commercial success remains uncertain[118] Manufacturing and Quality Control - The company intends to engage contract manufacturers for drug production, but risks include inability to meet regulatory standards and potential breaches of contract[186] - Manufacturing difficulties could delay clinical trials and increase costs, jeopardizing the company's ability to provide drug candidates to patients[190] - The company is responsible for quality control by its manufacturers, and failures in this area could lead to significant regulatory restrictions[189] Strategic Partnerships and Collaborations - The company intends to seek strategic alliances, joint ventures, or acquisitions to enhance development and commercialization efforts[224] - The company may face significant competition in establishing strategic partnerships, which may be time-consuming, costly, and complex[225] - Delays in clinical trials or insufficient funding from collaborators could hinder the development of drug candidates[228] - Failure to secure collaborations may lead the company to undertake development activities independently, which could strain financial resources[230]

Financial Performance - Aptorum Group reported a net loss of $11.5 million in 2022, a significant decrease from a net loss of $27.1 million in 2021, primarily due to a gain on long-term investments of $5.6 million and a decrease in loss on investments in marketable securities of $7.9 million[8]. - Research and development expenses decreased to $9.2 million in 2022 from $10.9 million in 2021, attributed to reduced contracted research organization services as the company prepares for Phase 2 of its lead projects[8]. - General and administrative fees slightly decreased to $5.2 million in 2022 from $5.4 million in 2021, mainly due to reduced payroll expenses from a decrease in staff[8]. - Legal and professional fees increased to $2.9 million in 2022 from $2.6 million in 2021, due to more consulting services engaged during the year[9]. - Accumulated deficit increased from $(55,537,515) to $(65,337,075), a deterioration of approximately 17.5%[19]. Cash and Assets - As of December 31, 2022, Aptorum Group had $5.0 million in cash and restricted cash, down from $8.3 million as of December 31, 2021, primarily due to cash used in operating activities[9]. - Cash and cash equivalents decreased from $8,131,217 to $1,882,545, a decline of about 76.8%[19]. - Total current assets decreased from $12,688,300 to $7,067,802, a decline of approximately 44.8%[19]. - Total assets decreased from $21,907,243 to $20,867,371, a decline of about 4.7%[19]. Liabilities and Equity - Total liabilities increased significantly from $4,401,121 to $13,034,066, representing an increase of about 195.5%[19]. - Total equity attributable to shareholders decreased from $23,607,345 to $15,712,094, a reduction of approximately 33.5%[19]. - Accounts payable and accrued expenses rose from $4,172,565 to $6,166,807, an increase of approximately 47.8%[19]. - Non-controlling interests increased from $(6,101,223) to $(7,878,789), a change of approximately 29.1%[19]. Investments and Corporate Actions - Long-term investments increased from $4,156,907 to $9,744,958, representing an increase of about 134.0%[19]. - The company entered into a non-binding Letter of Intent to acquire 100% of URF Holding Group Limited, which may result in a reverse takeover and continued listing on Nasdaq[7]. - The company effectuated a ten-for-one share consolidation on January 23, 2023, changing the par value of Class A and Class B Ordinary Shares[5]. - The company executed a 1 for 10 reverse stock split effective January 23, 2023[20]. Clinical Development - The company completed Pre-IND discussions with the US FDA for its lead project ALS-4, targeting IND clearance for Phase II clinical trials in the United States[3]. - The End of Phase 1 meeting for SACT-1 with the US FDA was completed, with the FDA agreeing on the proposed clinical development plan for pediatric neuroblastoma treatment[4]. Commercialization - NativusWell® commenced commercialization in China through JD.com, one of the largest e-commerce platforms in the country[4].

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 20-F ☐ REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2019 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☐ SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Date of ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 20-F ☐ REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2018 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 OR ☐ SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Date of ...