Skye Bioscience, Inc.

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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11250 El Camino Real, Suite 100, San Diego, CA 92130, (858) 410-0266

2026 Stockholder Letter

To the Stockholders of Skye Bioscience, Inc.:

2025 was an important year for Skye. We moved nimacimab to proof-of-concept in obesity and, in doing so, generated clinical, translational and preclinical findings that sharpened our development path and strengthened our conviction in peripheral CB1 inhibition as a differentiated metabolic mechanism.

Our objective remains straightforward: build a therapy that can complement today’s incretin-based medicines by improving the quality, durability and tolerability of weight loss. We believe the latest CBeyond™ data, combined with our translational work, support that strategy and provide a clearer roadmap for what comes next.

What We Learned from CBeyond™

CBeyond delivered an important clinical signal for nimacimab in combination with semaglutide. At 26 weeks, the combination arm showed clinically meaningful additional weight loss versus semaglutide alone, along with statistically significant improvements in waist circumference and lean-to-fat mass ratio. In the 52-week extension, the combination arm reached 22.3% mean weight loss, with no plateau observed.

We also believe the safety profile remains encouraging. Through 52 weeks, nimacimab 200 mg showed placebo-like tolerability, with no nimacimab-associated neuropsychiatric signal observed to date and no additive gastrointestinal burden when used in combination with semaglutide.

A Clearer Development Path

Equally important, the monotherapy arm helped answer a development question. Based on the full dataset and our biodistribution work, we believe the 200 mg weekly dose underexposed key peripheral tissues. In other words, the result appears to reflect dose and exposure, not a limitation of the pathway itself.

That learning has shaped our next steps. We have initiated a higher-dose expansion of CBeyond to generate safety and pharmacokinetic data at greater exposures, and we are continuing to monitor closely for neuropsychiatric events while preserving nimacimab’s central-sparing profile.

We also saw encouraging off-treatment follow-up data. In the combination cohort, participants regained less weight than those who had received semaglutide alone, and body composition findings suggested fat-mass loss was maintained during the off-therapy period. We believe those observations further support nimacimab’s differentiated mechanism.

Preparing for Phase 2b

During 2025 and into 2026, we have continued to translate these findings into a practical development plan. We are incorporating FDA feedback into our Phase 2b design, advancing a high-concentration formulation and working with Halozyme, Inc. to evaluate ENHANZE® technology to support higher-exposure subcutaneous delivery.

Our goal for 2026 is to answer the key value-driving question for nimacimab: what exposure and duration of peripheral CB1 engagement are required to deliver clinically meaningful efficacy with an acceptable safety margin? We believe the expansion study is designed to help us answer that question efficiently and position the program for its next stage of development.

Expanding the Platform

Beyond nimacimab as a standalone asset, we also reported early proof-of-concept for our first antibody-peptide conjugate program. These data support a broader view of Skye as a multi-mechanism metabolic company, using a clinically characterized antibody backbone to pursue combination-like biology in new formats.

We see this work as an extension of the same strategy that guides our lead program: focus on differentiated biology, develop with discipline and create assets that can fit into the real-world treatment landscape for obesity and related metabolic disease.

Executing with Discipline

We continue to manage the business with focus and capital discipline, aligning our operating plan around the studies, formulation work and regulatory steps that matter most. Our team remains concentrated on translating the current data into a clear dose-selection path, practical product profile and Phase 2b readiness.

Looking Ahead

The coming year is about execution. We expect additional data from the CBeyond™ expansion study, continued progress on subcutaneous delivery and further advancement of our bioconjugation platform. Each of these steps is intended to strengthen the long-term value of the franchise while keeping our near-term priorities clear.

We appreciate the continued support of our stockholders as we advance this work. We believe Skye is better positioned today than it was a year ago, with a more informed clinical plan, a sharper product strategy and a broader innovation platform.

Thank you for your support.

Sincerely,

Chief Executive Officer

The accompanying proxy statement, including this letter from our CEO, contains forward-looking statements based upon current expectations that involve risks, uncertainties and assumptions. For more information, see the section in the proxy statement entitled “Forward-Looking Statements.”

11250 El Camino Real, Suite 100, San Diego, CA 92130, (858) 410-0266

Dear Stockholder:

NOTICE OF 2026 ANNUAL MEETING OF STOCKHOLDERS AND PROXY STATEMENT

Date:

May 26, 2026

Time:

10:00 a.m., PT

Place:

Virtual Internet

YOUR VOTE

IS IMPORTANT

Please vote your shares whether or not you plan to participate in the meeting.

The 2026 Annual Meeting of Stockholders (the “Annual Meeting”) of Skye Bioscience, Inc., a Nevada corporation (the “Company”, “we,” “us,” and “our”), will be held as a virtual meeting via live webcast on the Internet on Tuesday, May 26, 2026, at 10:00 a.m. Pacific Time. Because the Annual Meeting is completely virtual and being conducted via the Internet, you will not be able to attend in person, but you will be able to participate online and submit your questions during the meeting by visiting www.virtualshareholdermeeting.com/SKYE2026. For instructions on how to participate in and vote your shares during the Annual Meeting, see the information in the accompanying Proxy Statement in the Section entitled, “General Information about the Annual Meeting and Voting – How can I participate in and vote at the Annual Meeting?”

The Annual Meeting is being held for the following purposes:

The foregoing items of business are more fully described in the attached proxy statement, which forms a part of this notice and is incorporated herein by reference. Our Board of Directors has fixed the close of business on April 2, 2026, as the record date for the determination of stockholders entitled to notice of and to vote at the Annual Meeting or any adjournment or postponement thereof.

We have elected to take advantage of the Securities and Exchange Commission (“SEC”) rules that allow us to use the Internet as our primary means of providing our proxy materials to stockholders. The electronic delivery of our proxy materials will significantly reduce our printing and mailing costs and the environmental impact of the circulation of our proxy materials.

Consequently, most stockholders will not receive paper copies of our proxy materials, unless requested. We will instead send to these stockholders a Notice of Internet Availability of Proxy Materials with instructions for accessing and reviewing the proxy materials on the Internet, including our proxy statement and annual report, and for voting via the Internet. The Notice of Internet Availability of Proxy Materials also provides information on how stockholders may obtain paper copies of our proxy materials free of charge, if they so choose.

The Notice of Internet Availability of Proxy Materials also provides the date and time of the Annual Meeting; the matters to be acted upon at the meeting and our board of directors’ recommendation with regard to each matter; a toll-free number, an email address and a website where stockholders may request a paper or email copy of the proxy statement, our annual report to stockholders and a form of proxy relating to the Annual Meeting; information on how to access the form of proxy; and information on how to participate in the Annual Meeting.

Your vote is important. Whether or not you expect to participate in our Annual Meeting, please vote as soon as possible in advance of the Annual Meeting by Internet or telephone as described in the accompanying proxy materials or, if you request that the proxy materials be mailed to you, by signing, dating and returning the proxy card enclosed with those materials. If you plan to participate in our Annual Meeting and wish to vote your shares during the Annual Meeting, you may do so at any time before the proxy is voted.

All stockholders are cordially invited to participate in the meeting. We appreciate your continued support of the Company.

By Order of the Board of Directors,

Punit Dhillon

Chief Executive Officer and Director

San Diego, California

April 16, 2026