Table of Contents As filed with the Securities and Exchange Commission on March 27, 2024 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 (Primary Standard Industrial Nevada 2834 45-0692882 Classification Code Number) (I.R.S. Employer Identification Number) 11250 El Camino Real, Suite 100 San Diego, CA 92130 FORM S-1 REGISTRATION STATEMENT Under THE SECURITIES ACT OF 1933 SKYE BIOSCIENCE, INC. (Exact Name of Registrant as Specified in its Charter) (State or other ...

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 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, 2023 ☐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: 000-55136 Skye Bioscience, Inc. (Exact name of registrant as specified in its charter) | --- | --- | |---------- ...

Financial Performance - As of September 30, 2023, Skye Bioscience had a working capital of $1,567,627 and an accumulated deficit of $99,962,619[117]. - For the nine months ended September 30, 2023, the company incurred losses from operations of $30,648,916, compared to $9,028,662 for the same period in 2022, representing a 239% increase in losses[117]. - The net loss for the three months ended September 30, 2023, was $24,945,834, compared to $3,127,283 for the same period in 2022, indicating a significant increase in losses[117]. - The company incurred net losses of $33,224,854 for the nine months ended September 30, 2023, compared to $9,589,960 for the same period in 2022[135]. - The company expects to continue incurring significant losses and negative cash flows as it advances drug candidates in development and supports its corporate infrastructure[135]. - The net loss for the nine months ended September 30, 2023, was $33,224,854, partially offset by non-cash charges totaling $23,476,130[140]. Research and Development - Research and development expenses for the three months ended September 30, 2023, decreased by $527,071 (30%) to $1,254,653 compared to $1,781,724 in 2022[124]. - Research and development expenses for the nine months ended September 30, 2023 decreased by $246,564 (6%) to $4,227,967 compared to the same period in 2022, mainly due to reduced clinical contract costs and consulting expenses[129]. - The Phase 1 clinical study of SBI-100 Ophthalmic Emulsion (OE) was completed in June 2023, with a reported 23% mean reduction in intraocular pressure in a subset of participants[112]. - Skye plans to initiate a Phase 2 study of nimacimab for cardiometabolic disease, including obesity, in the first half of 2024[112]. - The Phase 2 study of SBI-100 OE will include 54 patients with primary open-angle glaucoma or ocular hypertension, with interim analysis expected in the first half of 2024[112]. - Skye's clinical pipeline includes nimacimab, a first-in-class molecule targeting the CB1 receptor, which is expected to add significant value to the company's offerings[115]. Expenses and Costs - General and administrative expenses for Q3 2023 increased by $1,095,341 (96%) to $2,235,899 compared to Q3 2022, driven by higher board fees, professional fees, and travel costs due to the BRB Acquisition and PIPE Financing[126]. - General and administrative expenses for the nine months ended September 30, 2023 rose by $803,446 (18%) to $5,357,577, influenced by increases in board and professional fees due to various financing activities[131]. - Total other expense for Q3 2023 was $240,068, an increase of $35,067 (17%) from $205,001 in Q3 2022, primarily due to increased interest expenses related to the Cunning Lawsuit[127]. - Total other expense for the nine months ended September 30, 2023 was $2,572,338, a significant increase of $2,016,181 (363%) from $556,157 in the same period of 2022, primarily due to debt conversion inducement expenses[134]. - Estimated legal contingency for the nine months ended September 30, 2023 was $(151,842), reflecting a reduction in legal fees related to the Cunning Lawsuit[133]. Financing and Cash Flow - The company raised $11,734,947 through PIPE Financing, issuing 2,989,981 shares of common stock and 2,325,537 warrants with an exercise price of $5.16[138]. - Cash provided by financing activities included $4,973,684 from a Convertible Note and $11,734,947 from PIPE Financing, net of issuance costs[145]. - The company reported a net cash used in operating activities of $10,107,460 for the nine months ended September 30, 2023, compared to $7,872,550 for the same period in 2022, reflecting an increase in operating losses[139]. - The company entered into a loan agreement for $250,000, which was later converted into an investment in PIPE Financing[138]. - The company has no outstanding warrants or debt as of September 30, 2023, following the exercise of all outstanding warrants by Sciences[138]. Operational Challenges - The company has implemented cost-cutting measures, including deferring employee payments and postponing non-essential studies, to extend its cash runway[136]. - The company faces substantial doubt regarding its ability to continue as a going concern due to recurring operating losses and the need for additional financing[138]. - The company expects to collect the remainder of the value from the divestiture of EHT's assets through 2026, but there are significant risks regarding the timing and realization of these assets[136].

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 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: 000-55136 Skye Bioscience, Inc. _____________________________________________________________ (Exact name of regis ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 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: 000-55136 Skye Bioscience, Inc. _____________________________________________________________ (Exact name of regi ...

Financial Performance - The net loss for the year ended December 31, 2022, was $19,481,602, compared to a net loss of $8,522,182 for the year ended December 31, 2021, indicating a significant increase in losses [175]. - As of December 31, 2022, the accumulated deficit was $66,737,765, with negative cash flows from operations amounting to $12,744,072 [175]. - The company incurred operating losses and negative cash flows from operations of $12,744,072 in 2022, compared to $6,474,888 in 2021, reflecting a net loss from operations of $19,481,602 [203][204]. - The company expects to continue incurring significant losses and negative cash flows through 2023, primarily to advance drug candidates into clinical development [198]. - For the year ended December 31, 2022, the company reported a net other expense of $1,163,129, primarily due to interest expense and wind-down costs associated with the Acquisition, representing a 73% increase from $672,368 in 2021 [197]. Cash and Liquidity - The company had unrestricted cash of $1,244,527 as of December 31, 2022, down from $8,983,007 as of December 31, 2021, reflecting a decrease in liquidity [175]. - As of December 31, 2022, the company had an accumulated deficit of $66,737,765 and a working capital deficit of $3,175,408, with unrestricted cash decreasing to $1,244,527 from $8,983,007 in 2021 [200]. - The company anticipates that without additional funding during the second quarter of 2023, it may not have sufficient funds to meet its obligations and continue operations [200]. - The closing payment from the sale of VDL in February 2023 provided the company with $5,547,000, extending its cash runway into the second quarter of 2023 [168]. - Cash provided by investing activities in 2022 was $5,214,395, mainly from cash proceeds received from the Acquisition, while cash used in financing activities was $(208,794) [203][205][206]. Research and Development - Research and development expenses for the year ended December 31, 2022, were $6,011,805, an increase of 105% compared to $2,931,437 in 2021 [193]. - The increase in research and development expenses was primarily due to $2,348,534 for the manufacturing of Phase 1 clinical trial material for SBI-100 OE [193]. - The company expects to incur future research and development expenditures to support preclinical and clinical studies [193]. - SBI-100 OE is being developed to treat glaucoma and ocular hypertension, utilizing a proprietary nanoemulsion formulation [170]. - SBI-200 is being researched for its potential therapeutic applications in various eye diseases, with early studies showing promising properties [173]. - The Phase 1 trial for SBI-100 OE commenced in December 2022, with expectations to complete enrollment in the first half of 2023 [172]. - The company expects to begin its Phase 2 clinical trial for SBI-100 OE in mid-2023, following FDA clearance of its Investigational New Drug application [172]. Expenses and Legal Contingencies - General and administrative expenses for the year ended December 31, 2022, were $6,094,617, reflecting a 24% increase from $4,916,277 in 2021 [194]. - The increase in general and administrative expenses was mainly due to $746,952 in employee wages and board fees related to new hires and bonuses [194]. - The increase in general and administrative expenses also included $732,529 in professional and legal fees associated with preliminary diligence costs related to an acquisition [194]. - An estimated legal contingency of $6,205,310 was recorded for the year ended December 31, 2022, related to the Cunning Lawsuit [196]. - The company recognized an estimated legal contingency of $6,205,310 related to the Cunning Lawsuit, which increased overall legal costs for the year ended December 31, 2022 [200]. Acquisitions and Assets - The acquisition of EHT was completed on November 10, 2022, with an exchange ratio of 1.95 shares of Skye Bioscience common stock for each share of EHT common stock [168]. - The company acquired net assets with an estimated fair value of $15,045,412 upon closing the Acquisition, receiving $6,784,057 in cash [200]. - The company evaluates acquisitions to determine if they should be accounted for as a business combination or asset acquisition, requiring significant judgment [187]. Going Concern - The company’s independent registered public accounting firm expressed substantial doubt about its ability to continue as a going concern due to recurring operating losses [200]. - The outstanding principal balance under the Amended Credit Agreement was $1,848,375 as of December 31, 2022, with an extension of the maturity date to February 28, 2023 [200].

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2022 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: 000-55136 Skye Bioscience, Inc. _____________________________________________________________ (Exact name of ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2022 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: 000-55136 Skye Bioscience, Inc. _____________________________________________________________ (Exact name of regis ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2022 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: 000-55136 Skye Bioscience, Inc. _____________________________________________________________ (Exact name of regi ...

FORM 10-K ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Table of Contents For the fiscal year ended December 31, 2021 ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 For the transition period from __________ to __________ Commission File Number: 000-55136 Skye Bioscience, Inc. | Title of each class: | Name of each exchange on which registered: | | --- | ...