UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 (Mark one) FORM 10-K ☒ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from to Commission file number: 000-24477 Diffusion Pharmaceuticals Inc. (Exact Name of Registrant as specified in its Charter) Delaware (State or Other Jurisdiction of ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark one) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2021 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ______________. Commission file number: 000-24477 DIFFUSION PHARMACEUTICALS INC. (Exact name of registrant as specified in its charter) Delawa ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark one) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2021 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ______________. Commission file number: 000-24477 DIFFUSION PHARMACEUTICALS INC. (Exact name of registrant as specified in its charter) Delaware 30 ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark one) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2021 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ______________. Commission file number: 000-24477 DIFFUSION PHARMACEUTICALS INC. (Exact name of registrant as specified in its charter) Delaware 3 ...

Drug Development and Regulatory Challenges - The company is currently focused on the development of its lead product candidate, TSC, with significant resources allocated to this effort [179]. - The drug development process is expensive and uncertain, with many candidates failing to receive regulatory approval [180]. - The company has no products approved for sale and may never obtain regulatory approval for TSC or other candidates [188]. - The timeline for clinical trials may face delays due to various factors, including regulatory reviews and enrollment rates [181]. - Regulatory approval processes are complex, and the company may face additional requirements or delays in obtaining approvals [192]. - The company faces risks related to potential undesirable side effects of product candidates, which could delay regulatory approval and limit commercial potential [212]. - The company has only manufactured TSC in small quantities for trials and will need to scale up production significantly for commercialization [201]. - The company completed its TSC COVID Trial in February 2021, conducted in Romania, but there is uncertainty regarding the acceptance of data from trials conducted outside the U.S. by the FDA [210]. Manufacturing and Supply Chain Risks - The company relies entirely on third parties for manufacturing and supply, which poses risks to maintaining adequate drug supply [196]. - Current manufacturing challenges include delays due to the COVID-19 pandemic, impacting the production of TSC [198]. - The company is dependent on a sole supplier for the manufacture of TSC's active pharmaceutical ingredient (API), limiting options for troubleshooting [199]. - Any disruption in relationships with manufacturing partners could lead to significant delays and increased costs [198]. - The company relies on third-party contract manufacturers and suppliers, which exposes it to risks related to the misappropriation of trade secrets and difficulties in importing products due to regulatory requirements [202]. - The company expects to continue relying on third-party CROs for clinical trials and development processes, which may impact the timely development and commercialization of product candidates if these partners do not meet requirements [204]. Intellectual Property and Competition - The company’s issued U.S. patents related to TSC begin to expire in 2023, which may occur before obtaining regulatory approval for commercialization [220]. - The company may face competition from biosimilar medications once its patents expire, impacting its market position [220]. - The company’s ability to maintain patent protection is critical for the successful development and commercialization of TSC and other product candidates [225]. - The pharmaceutical industry is characterized by intense competition, and the company must secure valid patents to protect its innovations and prevent third-party infringement [226]. - The company has a patent portfolio that includes patents and applications in the U.S. and other major markets, but it may not have patent protection for every aspect of its technology [227]. - The patent application process is expensive and time-consuming, and the company may fail to identify patentable aspects of inventions in a timely manner [229]. - The natural expiration of a patent in the U.S. is generally 20 years after filing, with some patents related to TSC set to expire beginning in 2023, potentially affecting competitive position [231]. - The company may face challenges in protecting intellectual property rights in foreign jurisdictions, particularly in developing countries [232]. - Proprietary trade secrets and unpatented know-how are crucial to the business, but there is a risk of third parties obtaining this information despite protective measures [233]. Financial Position and Funding Needs - The company may require additional capital to fund operations, with existing cash resources expected to support activities through 2023, but future financing needs remain uncertain [250]. - The company has previously suspended enrollment in clinical trials due to inadequate resources before completing funding offerings [251]. - Future funding requirements will depend on various factors, including the number and development stage of product candidates and the costs associated with clinical trials and regulatory approvals [252]. - The company has generated no revenue from product sales and has incurred significant losses since inception, with expectations of continued losses for the foreseeable future [254]. - As of December 31, 2020, the company had $11.7 million in federal and state NOL carryforwards available to reduce future taxable income, which will begin expiring in 2034 [268]. - The company currently has only two product candidates under active development: TSC and DFN-529, with plans to potentially in-license or acquire additional candidates in the future [265]. - The company has sufficient cash resources to fund TSC Oxygenation Trials and other operating expenses through 2023, but will need to raise additional funds for future operations and clinical trials [280]. - The company plans to finance operations through equity issuances, debt arrangements, and potential licensing or partnerships [280]. - A substantial number of shares of common stock may be issued at any time, with a previous issuance of 33,658,538 shares in February 2021 [281]. - The company may seek additional capital through debt financings, strategic partnerships, and licensing arrangements, which could impose restrictions on operations [283]. Organizational and Market Risks - The company has a limited operating history and faces risks and uncertainties typical of clinical stage biotechnology companies [255]. - The company has incurred substantial net losses and negative cash flow from operations, with ongoing expenses related to research and development [256]. - The company anticipates needing to increase its workforce to support the development of TSC and other product candidates, currently employing 13 full-time and one part-time employee [259]. - Future profitability will depend on the successful development and commercialization of TSC and other product candidates, which may require significant costs [257]. - The company may face challenges in attracting and retaining qualified personnel due to competition within the biotechnology and pharmaceutical industries [261]. - The company has historically relied on independent contractors for critical functions, which may pose risks if these relationships cannot be effectively managed [262]. - Organizational documents contain anti-takeover provisions that may make acquisitions or proxy contests more difficult, potentially depressing stock price [284]. - The company may issue undesignated preferred stock without stockholder approval, which could include rights superior to common stock holders [284]. - The Court of Chancery of the State of Delaware is designated as the exclusive forum for certain stockholder actions, which may limit stockholders' ability to obtain a favorable judicial forum [285]. - Limitations on stockholder rights imposed by organizational provisions could depress the trading price of common stock [286]. - As a "smaller reporting company," the company is not required to provide certain market risk disclosures [353].

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UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark one) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2020 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ______________. Commission file number: 000-24477 DIFFUSION PHARMACEUTICALS INC. (Exact name of registrant as specified in its charter) Delawa ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark one) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2020 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ______________. Commission file number: 000-24477 DIFFUSION PHARMACEUTICALS INC. (Exact name of registrant as specified in its charter) Delaware 30 ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark one) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2020 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ______________. Commission file number: 000-24477 DIFFUSION PHARMACEUTICALS INC. (Exact name of registrant as specified in its charter) Delaware 3 ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Form 10-K (Mark one) ☒ 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 For the transition period from to Commission file number: 000-24477 DIFFUSION PHARMACEUTICALS INC. (Exact Name of Registrant as specified in its Charter) | --- | --- | --- | |------------------- ...