To Our Valued Stockholders:

We are writing to reaffirm our strong belief that Seneca Biopharma's proposed merger with Leading Biosciences is in the best interests of all stockholders and urge your support at the Company's Special Meeting scheduled for April 9, 2021.

After a thorough review process that included an evaluation of multiple alternatives, Seneca's Board ultimately concluded the Merger offers the most compelling opportunity for its stockholders. Seneca's board recommends voting in favor of the proposals (including the reverse stock split) for the following reasons:

• The post-Merger combined company (to be re-named Palisade Bio) will be well-positioned to pursue Leading Biosciences' pipeline of novel therapeutics

• LBS's lead candidate, LB1148, has demonstrated efficacy signals in three clinical trials
• LB1148 is aimed at multiple indications each with large addressable markets
• FDA fast track designation has already been granted to expedite regulatory review of LB1148 based on its potential to treat serious conditions and fill unmet medical needs
• LB1148 has a clear regulatory approval pathway, including Phase 3 clinical trials scheduled to commence in 2021 with multiple potentially value-creating clinical data readouts over the following 12 to 18 months
• Attractive co-development and licensing agreement with Newsoara provides potential for approvals for and access to the Chinese market
• LBS plans to build a pipeline of new candidates on its integrated protease assay platform to diversify the company's risk profile and create potential for multiple shots on goal

• Palisade Bio has capital support from a regional hospital system and Altium Capital and transaction has the endorsement of leading proxy advisory firm ISS

• After reviewing Seneca's proposed Merger with LBS, Institutional Shareholder Services ("ISS") has recommended stockholders vote FOR both the Merger and the reverse stock split
• LBS has raised in excess of $35 million from life sciences investors since inception, with a hospital system as its largest investor to date, helping to validate the market potential and benefits to hospitals
• Altium Capital has committed to investing $20.0 million in Palisade prior to the closing of the Merger
• Listing on Nasdaq will enable Palisade Bio to attract a broader range of stockholders, including institutional investors that are averse to companies not listed on a major exchange

• Accomplished and proven management team and Board of Directors

• Broad base of pharmaceutical expertise and successes
• Medical, clinical, and regulatory expertise leading to successes in clinical studies

• The Merger provides a compelling value proposition for Seneca's stockholders

• Following the Merger, Seneca stockholders will own ~26% of Palisade Bio
• Seneca has negotiated a Contingent Value Right ("CVR") that preserves the ability of its stockholders, and certain of its warrant holders, to potentially recognize additional value if Seneca's legacy assets are sold or licensed within 18 months of the merger closing. The CVR would entitle Seneca stockholders to 80% of the monetization of the company's assets. However, only upon completion of the merger will the CVR be issued to Seneca stockholders of record as of the record date. If the merger is not completed, the CVR will not be created and Seneca stockholders will not receive one. If the merger is completed, Seneca will announce the timing and protocol for receiving the CVR.

As indicated in the Company's proxy statement (link: https://www.sec.gov/Archives/edgar/data/0001357459/000117184321000977/f424b3_021121.htm), Seneca's Board recommends stockholders vote FOR all proposals at the Special Meeting. Proposals #1 and #2 are critical because the Merger cannot be consummated without their approval. We therefore urge all stockholders to vote FOR the merger for the reasons outlined above, including proposal #1, the reverse stock split, which is a pre-requisite to close the merger and enables Palisade Bio to meet Nasdaq's listing requirements.

Recent changes in how some brokerage firms cast votes on behalf of their clients has impacted voter turnout at Seneca and all public companies with a meaningful retail shareholder base. As a result, based on the higher vote requirement of a majority of all outstanding shares needed to approve the reverse stock split (compared to merely a majority of votes cast required for all other proposals), Seneca adjourned the Special Meeting until April 9, 2021 to enable additional time for stockholders to consider and vote on all proposals.

Seneca's Board, as well as LBS and Altium, remains fully supportive of the Merger. We urge all stockholders to support it as well by voting FOR all proposals at the Special Meeting. Regardless of the number of shares of our common stock that you own, even if you no longer hold Seneca shares, your vote is very important and will be greatly appreciated. Thank you for your continued support, interest, and investment in Seneca Biopharma, Inc.

Sincerely,

Seneca Biopharma

PLEASE VOTE

YOUR VOTE MAY IMPACT THE VALUE OF YOUR INVESTMENT AND THE FUTURE OF SENECA BIOPHARMA, INC.

According to our latest records, we may not have received your vote – PLEASE VOTE TODAY BY CALLING TOLL-FREE: 1-855-682-2019!

About Seneca Biopharma, Inc.

Seneca is a clinical-stage biopharmaceutical company developing novel treatments for diseases of high unmet medical need. On December 17, 2020, Seneca announced that it had entered into a definitive merger agreement with LBS, a privately held company focused on developing novel therapeutics to improve human health through therapeutic protection of the gastrointestinal mucosal barrier.

About Leading BioSciences, Inc.

LBS is developing novel therapeutics designed to improve human health through therapeutic protection of the gastrointestinal mucosal barrier. LBS' initial focus is combatting the interruption of GI function (ileus) following major surgery in order to reduce recovery times and shorten the duration of patient hospital stays. Additionally, LBS believes that its investigational therapies have the potential to prevent the formation of postoperative adhesions (reducing hospital re-admissions and additional surgeries), as well as to address the myriad health conditions and complications associated with chronic disruption of the gastrointestinal mucosal barrier.