To the Stockholders of Caladrius Biosciences, Inc. and Cend Therapeutics, Inc.:

Caladrius Biosciences, Inc. (“Caladrius”) and Cend Therapeutics, Inc. (“Cend”) have entered into an Agreement and Plan of Merger and Reorganization (the “Merger Agreement”) pursuant to which a wholly owned subsidiary of Caladrius will merge with and into Cend, with Cend surviving as a wholly owned subsidiary of Caladrius (the “Merger”).

At the effective time of the Merger (the “Effective Time”), each share of Cend’s common stock, par value $0.00001 per share (“Cend Common Stock”), and each share of Cend’s preferred stock, par value $0.00001 per share (“Cend Preferred Stock,” together with the Cend Common Stock, the “Cend Capital Stock”), outstanding immediately prior to the Effective Time will be converted into the right to receive approximately 8.5623 shares of Caladrius’ common stock, par value $0.001 per share (“Caladrius Common Stock”), subject to adjustment to account for the effect of a reverse stock split of Caladrius Common Stock, at a ratio mutually agreed to by Caladrius and Cend in the range of one new share for every five to fifteen shares outstanding (or any number in between) (the “Reverse Stock Split”), to be implemented prior to the consummation of the Merger as discussed in this proxy statement/prospectus/information statement, and further adjusted based on Caladrius’ net cash and Cend’s unpaid transaction costs immediately prior to the closing of the Merger (the “Exchange Ratio”). Because Caladrius’ net cash balance and Cend’s unpaid transaction costs will not be determined until immediately prior to the closing of the Merger, and because the number of shares of Caladrius Common Stock issuable to Cend is determined based on Caladrius’ net cash balance and Cend’s unpaid transaction costs immediately prior to the closing of the Merger, Caladrius’ stockholders cannot be certain of the exact number of shares of Caladrius Common Stock that will be issued to Cend stockholders when Caladrius’ stockholders vote on the proposals at the Annual Meeting of Caladrius stockholders. Caladrius will assume outstanding and unexercised options to purchase shares of Cend Common Stock granted under Cend’s 2016 Equity Incentive Plan, and each such option will be converted into an option to purchase shares of Caladrius Common Stock, with the number of shares of Caladrius Common Stock subject to such option and the exercise price being appropriately adjusted to reflect the Exchange Ratio. Caladrius stockholders will continue to own and hold their existing shares of Caladrius Common Stock. At the Effective Time, each (i) option or other right to purchase shares of Caladrius Common Stock issued by Caladrius (a “Caladrius Option”), (ii) restricted stock unit covering shares of Caladrius Common Stock issued or granted by Caladrius, which for the avoidance of doubt, shall include a performance stock unit covering shares of Caladrius Common Stock issued or granted by Caladrius and (iii) award of shares of Caladrius Common Stock subject to forfeiture and certain vesting criteria, in each case, that is outstanding and unexercised immediately prior to the Effective Time, whether or not vested, shall survive the closing of the Merger and remain outstanding in accordance with its terms.

Immediately following the consummation of the Merger, Cend’s stockholders are expected to own approximately 50% of the outstanding shares of Caladrius Common Stock, and Caladrius’ stockholders are expected to own approximately 50% of the outstanding shares of Caladrius Common Stock, subject to adjustment of the Exchange Ratio as set forth in the Merger Agreement.

Shares of Caladrius Common Stock are currently listed on The Nasdaq Capital Market under the symbol “CLBS.” Prior to consummation of the Merger, Caladrius intends to file a notification form for the listing of additional shares with respect to the shares of Caladrius Common Stock to be issued to the holders of Cend Capital Stock in the Merger; provided, however, that in the event that Caladrius is so required pursuant to The Nasdaq Stock Market, LLC’s (“Nasdaq”) “reverse merger” rules, Caladrius will file an initial listing application with Nasdaq. After completion of the Merger, Caladrius will be renamed “Lisata Therapeutics, Inc.” and expects to trade on The Nasdaq Capital Market under the symbol “LSTA.” On June 14, 2022, the last trading day before the date of this proxy statement/prospectus/information statement, the closing sale price of Caladrius Common Stock was $0.50 per share.

Caladrius is holding an annual meeting of stockholders (the “Annual Meeting”) in order to obtain the stockholder approvals necessary to complete the Merger and related matters, hold an election of directors, hold a “say-on-pay” vote, and ratify the selection of an independent registered public accounting firm. At the Annual Meeting, which will be held at     , New York time, on     , 2022, via live webcast on the internet where you will be able to participate in the Annual Meeting, vote and submit your questions during the Annual Meeting by visiting www.virtualshareholdermeeting.com/CLBS2022SM, unless postponed or adjourned to a later date, Caladrius will ask Caladrius’ stockholders to, among other things, (i) adopt the Merger Agreement thereby approving the Merger and the issuance of Caladrius Common Stock pursuant to the Merger Agreement, (ii) approve an amendment to Caladrius’ amended and restated certificate of incorporation effecting the Reverse Stock Split, (iii) approve an amendment to Caladrius’ amended and restated certificate of incorporation changing Caladrius’ corporate name from “Caladrius Biosciences, Inc.” to “Lisata Therapeutics, Inc.,” (iv) elect three Class III directors to hold office until the 2025 annual meeting of Caladrius’ stockholders or until their successors are elected (provided, however, that if the Merger is completed, Caladrius’ board of directors will be reconstituted as provided in the Merger Agreement), (v) ratify the selection by the audit committee of the Caladrius board of directors of Grant Thornton LLP as the independent registered public accounting firm of Caladrius for its calendar year ending December 31, 2022, (vi) approve, on a non-binding advisory basis, the executive compensation of Caladrius’ named executive officers as disclosed in this proxy statement/prospectus/information statement and (vii) approve an amendment to the Caladrius Biosciences, Inc. 2018 Equity Incentive Compensation Plan (the “Plan”) that increases the number of shares of common stock that may be issued under the Plan by 5,000,000, each as described in this proxy statement/prospectus/information statement.

As described in this proxy statement/prospectus/information statement, certain of Cend’s stockholders who in the aggregate own 100% of the outstanding shares of Cend Series A Preferred Stock, approximately 88.8% of the outstanding shares of Cend Series B Preferred Stock and approximately 77.5% of the outstanding shares of Cend Capital Stock on an as converted to common stock basis (excluding shares held by Caladrius), and certain Caladrius stockholders who in the aggregate own approximately 1.8% of the outstanding shares of Caladrius Common Stock, are parties to support agreements with Caladrius and Cend, respectively, whereby such stockholders have agreed to vote in favor of the adoption or approval of the Merger Agreement, as applicable, and the approval of the transactions contemplated therein, including the Merger and the issuance of Caladrius Common Stock in the Merger pursuant to the Merger Agreement, respectively, subject to the terms of the support agreements. In addition, following the registration statement on Form S-4, of which this proxy statement/prospectus/information statement is a part, being declared effective by the U.S. Securities and Exchange Commission and pursuant to the conditions of the Merger Agreement, Cend’s stockholders who are party to the support agreements will each execute an action by written consent of Cend’s stockholders, referred to herein as the written consent, adopting the Merger Agreement, thereby approving the Merger and related transactions. Therefore, holders of a sufficient number of shares of Cend Capital Stock required to adopt the Merger Agreement will adopt the Merger Agreement, and no meeting of Cend stockholders is required to adopt the Merger Agreement and approve the Merger and related transactions and no meeting of Cend’s stockholders will be held. Nevertheless, all of Cend’s stockholders will have the opportunity to elect to adopt the Merger Agreement, thereby approving the Merger and related transactions, by signing and returning to Cend a written consent.

After careful consideration, the respective boards of directors of Caladrius and Cend have (i) determined that the transactions contemplated by the Merger Agreement are fair to, advisable and in the best interests of Caladrius or Cend, as applicable, and their respective stockholders, (ii) approved and declared advisable the Merger Agreement and the transactions contemplated thereby and (iii) determined to recommend, upon the terms and subject to the conditions set forth in the Merger Agreement, that its stockholders vote to adopt or approve, as applicable, the Merger Agreement and, therefore, approve the transactions contemplated therein. Caladrius’ board of directors recommends that its stockholders vote “FOR” the proposals described in this proxy statement/prospectus/information statement, and Cend’s board of directors recommends that its stockholders sign and return to Cend the written consent indicating their approval of the Merger and adoption of the Merger Agreement and related transactions.

More information about Caladrius, Cend and the proposed transaction is contained in this proxy statement/prospectus/information statement. Caladrius and Cend urge you to read this proxy statement/prospectus/information statement carefully and in its entirety. IN PARTICULAR, YOU SHOULD CAREFULLY CONSIDER THE MATTERS DISCUSSED UNDER THE SECTION ENTITLED “RISK FACTORS” IN THIS PROXY STATEMENT/PROSPECTUS/INFORMATION STATEMENT.

Caladrius and Cend are excited about the opportunities the Merger brings to both Caladrius’ and Cend’s respective stockholders, and thank you for your consideration and continued support.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this proxy statement/prospectus/information statement. Any representation to the contrary is a criminal offense.

This proxy statement/prospectus/information statement is dated     , 2022, and is first being mailed to Caladrius’ and Cend’s respective stockholders on or about     , 2022.

 

Dear Stockholders of Caladrius:

On behalf of the board of directors of Caladrius Biosciences, Inc., a Delaware corporation (“Caladrius”), we are pleased to deliver this proxy statement/prospectus/information statement for the proposed merger between Caladrius and Cend Therapeutics, Inc., a Delaware corporation (“Cend”), pursuant to which CS Cedar Merger Sub, Inc., a Delaware corporation and a wholly owned subsidiary of Caladrius, will merge with and into Cend, with Cend surviving as a wholly owned subsidiary of Caladrius (the “Merger”). The annual meeting of stockholders of Caladrius (the “Annual Meeting”) will be held on    , 2022, at    , New York time. The Annual Meeting will be held via live webcast on the internet. You will be able to participate in the Annual Meeting, vote and submit your questions during the Annual Meeting by visiting www.virtualshareholdermeeting.com/CLBS2022SM. You will not be able to attend the Annual Meeting in person. The Annual Meeting is being held for the following purposes:

Caladrius’ board of directors has fixed     , 2022, as the record date (the “Record Date”) for the determination of stockholders entitled to notice of, and to vote at, the Annual Meeting and any adjournment or postponement thereof. Only holders of record of shares of Caladrius’ common stock at the close of business on the Record Date are entitled to notice of, and to vote at, the Annual Meeting. At the close of business on the Record Date, there were      shares of Caladrius’ common stock outstanding and entitled to vote.

Your vote is important. The affirmative vote of the holders of a majority of the shares of Caladrius’ common stock having voting power present in person or represented by proxy at the Annual Meeting is required for approval of Proposal Nos. 1, 5, 6, 7 and 8. The affirmative vote of the holders of a majority of shares of Caladrius’ common stock having voting power outstanding on the Record Date for the Annual Meeting is required for approval of Proposal Nos. 2 and 3. With respect to Proposal No. 4, the three nominees receiving the most “FOR” votes (from the votes of shares present in person or represented by proxy and entitled to vote on the election of directors) will be elected. The approval of Proposal No. 1 is a condition to the completion of the Merger. Therefore, the Merger cannot be consummated without the approval of Proposal No. 1.

All Caladrius stockholders are cordially invited to participate in the online, live Annual Meeting. However, even if you plan to participate in the webcast Annual Meeting, we request that you vote by following the instructions in the Notice of Internet Availability of Proxy Materials that you previously received and submit your proxy by telephone or through the Internet or by mail as promptly as possible prior to the Annual Meeting to ensure that your shares of Caladrius stock will be represented at the Annual Meeting. Please note, however, that if your shares are held of record by a broker, bank or other nominee and you wish to vote at the Annual Meeting, you must obtain a proxy issued in your name from the record holder.

By Order of Caladrius’ board of directors,

David J. Mazzo, Ph.D.

Caladrius Biosciences, Inc.

Basking Ridge, New Jersey

    , 2022

CALADRIUS’ BOARD OF DIRECTORS HAS DETERMINED AND BELIEVES THAT EACH OF THE PROPOSALS OUTLINED ABOVE IS ADVISABLE TO, AND IN THE BEST INTERESTS OF, CALADRIUS AND ITS STOCKHOLDERS AND HAS APPROVED EACH SUCH PROPOSAL. CALADRIUS’ BOARD OF DIRECTORS RECOMMENDS THAT CALADRIUS STOCKHOLDERS VOTE “FOR” EACH SUCH PROPOSAL.

This proxy statement/prospectus/information statement incorporates important business and financial information about Caladrius that is not included in or delivered with this document. You may obtain this information without charge through the Securities and Exchange Commission (“SEC”) website (www.sec.gov) or upon your written or oral request by contacting Caladrius’ Corporate Secretary at Caladrius Biosciences, Inc., 110 Allen Road, 2^nd Floor, Basking Ridge, New Jersey 07920 or by calling (908) 842-0100.

To ensure timely delivery of these documents, any request should be made no later than     , 2022, to receive them before the Annual Meeting.

For additional details about where you can find information about Caladrius, please see the section entitled “Where You Can Find More Information” in this proxy statement/prospectus/information statement.

Except where specifically noted, the following information and all other information contained in this proxy statement/prospectus/information statement does not give effect to the proposed reverse stock split described in Proposal No. 2, beginning on page 189 in this proxy statement/prospectus/information statement (the “Reverse Stock Split”).

The following section provides answers to frequently asked questions about the Merger (as defined below). This section, however, provides only summary information. For a more complete response to these questions and for additional information, please refer to the cross-referenced sections.

At the effective time of the Merger (the “Effective Time”), each share of Cend’s common stock, par value $0.00001 per share (“Cend Common Stock”), and each share of Cend’s preferred stock, par value $0.00001 per share (“Cend Preferred Stock,” and together with Cend Common Stock, “Cend Capital Stock”) outstanding immediately prior to the Effective Time (excluding certain shares to be canceled pursuant to the Merger Agreement, and shares held by stockholders who have exercised and perfected appraisal rights or dissenters’ rights as more fully described in the section of this proxy statement/prospectus/information statement entitled “The Merger—Appraisal Rights and Dissenters’ Rights”) will be converted into the right to receive approximately 8.5623 shares of Caladrius’ common stock, par value $0.001 per share (“Caladrius Common Stock”), subject to adjustment to account for the Reverse Stock Split, and further adjusted based on Caladrius’ net cash and Cend’s unpaid transaction costs immediately prior to the closing (the “Closing”) of the Merger (the “Exchange Ratio”). Because Caladrius’ net cash balance and Cend’s unpaid transaction costs will not be determined until the Closing, and because the number of shares of Caladrius Common Stock issuable to Cend is determined based on Caladrius’ net cash balance and Cend’s unpaid transaction costs at Closing, Caladrius Stockholders (as defined below) cannot be certain of the exact number of shares that will be issued to Cend’s stockholders when Caladrius’ stockholders vote on the proposals at the annual meeting of stockholders of Caladrius Stockholders (the “Annual Meeting”). The Exchange Ratio is an estimate only and the final Exchange Ratio will be determined pursuant to a formula described in more detail in the Merger Agreement and in the attached proxy statement/prospectus/information statement. As a result of the Merger, current holders of shares of Cend Capital Stock (each holder of Cend Capital Stock, a “Cend Stockholder”) are expected to own, or hold rights to acquire, in the aggregate approximately 50% of the outstanding shares of Caladrius Common Stock and current stockholders of Caladrius (“Caladrius Stockholders”) are expected to own in the aggregate approximately 50% of the outstanding shares of Caladrius Common Stock and, in each case, following the Effective Time and subject to adjustment of the Exchange Ratio. After the consummation of the Merger, and assuming Caladrius Stockholders approve Proposal No. 3, Caladrius will change its corporate name to “Lisata Therapeutics, Inc.” as required by the Merger Agreement (the “Caladrius Name Change”).

The approval of the Merger and the issuance of Caladrius Common Stock pursuant to the Merger Agreement by the Caladrius Stockholders requires the affirmative vote of the holders of a majority of the shares of Caladrius Common Stock having voting power present in person or represented by proxy at the Annual Meeting.

The adoption of the Merger Agreement and the approval of the Merger and related transactions by the Cend Stockholders requires the affirmative vote (or written consent) of the holders of a majority of (a) the outstanding shares of Cend Common Stock and Cend Preferred Stock, voting together as one class, (b) the holders of a majority of the outstanding shares of Cend Series A Preferred Stock, voting as a separate class, (c) the holders of a majority of the outstanding shares of Cend Series B Preferred Stock, voting as a separate class and (d) holders of a majority of the outstanding shares of Cend Series D Preferred Stock, voting as a separate class. In addition to the requirement of obtaining such stockholder approvals and appropriate regulatory approvals, each of the other closing conditions set forth in the Merger Agreement must be satisfied or waived.

The presence, in person or represented by proxy, at the Annual Meeting of the holders of a majority of the shares of Caladrius Common Stock outstanding and entitled to vote at the Annual Meeting is necessary to constitute a quorum at the meeting. Abstentions and broker non-votes will be counted toward a quorum. The affirmative vote of a majority of the votes cast in person or by proxy at the Annual Meeting, assuming a quorum is present, is required for approval of Proposal No. 1.

The approval of Proposal No. 1 is a condition to the completion of the Merger. Therefore, the Merger cannot be consummated without the approval of Proposal No. 1.

Votes will be counted by the inspector of election appointed for the meeting, who will separately count “FOR,” “AGAINST” and “WITHHOLD” votes, abstentions and broker non-votes. Abstentions and broker non-votes will be treated as shares present for the purpose of determining the presence of a quorum for the transaction of business at the Annual Meeting. Abstentions and broker non-votes will not, however, be considered votes cast at the Annual Meeting and will therefore not have any effect with respect to Proposal No. 1.

As of June 13, 2022, certain Cend Stockholders who in the aggregate own 100% of the outstanding shares of Cend Series A Preferred Stock, approximately 88.8% of the outstanding shares of Cend Series B

Preferred Stock and approximately 77.5% of the outstanding shares of Cend Capital Stock on an as converted to common stock basis (excluding shares held by Caladrius), and certain Caladrius Stockholders who in the aggregate own approximately 1.8% of the outstanding shares of Caladrius Common Stock, are parties to support agreements with Caladrius and Cend, respectively, whereby such stockholders have agreed to vote their shares in favor of the adoption or approval, as applicable, of the Merger Agreement and the transactions contemplated therein, including the Merger and the issuance of Caladrius Common Stock to Cend Stockholders pursuant to the Merger Agreement, subject to the terms of the support agreements. In addition, following the registration statement on Form S-4, of which this proxy statement/prospectus/information statement is a part, being declared effective by the U.S. Securities and Exchange Commission (the “SEC”) and pursuant to the conditions of the Merger Agreement, Cend Stockholders who are party to the support agreements will each execute written consents approving the Merger and related transactions.

Therefore, holders of a sufficient number of shares of Cend Capital Stock required to adopt the Merger Agreement, thereby approving the Merger, have agreed to adopt the Merger Agreement via written consent. Cend Stockholders, including those who are parties to support agreements, are being requested to execute written consents providing such approvals.

For a more complete description of the closing conditions under the Merger Agreement, Caladrius urges you to read the section entitled “The Merger Agreement—Conditions to the Completion of the Merger” in this proxy statement/prospectus/information statement.

The approval of Proposal Nos. 2, 3, 4, 5, 6, 7 and 8 are not conditions to the Merger. Such proposals, together with Proposal No. 1, are referred to collectively in this proxy statement/prospectus/information statement as the proposals.

The approval of the Reverse Stock Split (Proposal No. 2) is required in order to avoid a potential delisting of Caladrius Common Stock from The Nasdaq Capital Market. However, the approval of the Reverse Stock Split (Proposal No. 2) is not a condition to closing the Merger and is also not conditioned upon the consummation of the Merger, and as such the Reverse Stock Split may be implemented by the Caladrius Board of Directors even if the Merger does not take place.

Caladrius Stockholders should understand, however, that if the Merger is completed, the effect of the approval of Proposal No. 4 will be limited since the composition of the Caladrius Board of Directors will be changed upon completion of the Merger in accordance with the Merger Agreement.

The election of Class III directors to the Caladrius Board of Directors requires a plurality of the votes cast at the Annual Meeting. The approval of the proposal to ratify the selection of an independent registered public accounting firm for the calendar year ending December 31, 2022 requires the affirmative vote of a majority of the votes cast in person or by proxy (not counting “abstentions” or “broker non-votes” as votes cast), assuming a quorum is present, at the Annual Meeting.

The presence, in person or represented by proxy, at the Annual Meeting of the holders of a majority of the shares of Caladrius Common Stock outstanding and entitled to vote at the Annual Meeting is necessary to constitute a quorum at the meeting. Abstentions and broker non-votes will be counted toward a quorum. The affirmative vote of a majority of the votes cast in person or by proxy at the Annual Meeting, assuming a quorum is present, is required for approval of Proposal Nos. 5, 6, 7 and 8. The affirmative vote of the holders of a majority of shares of Caladrius Common Stock having voting power outstanding on    , 2022 (the “Record Date”) is required for approval of Proposal Nos. 2 and 3. Broker non-votes will not be counted towards the vote total for Proposal Nos. 5, 6, 7 and 8. Abstentions and broker non-votes will have the same effect as a vote “AGAINST” Proposal Nos. 2 and 3. With respect to Proposal No. 4, the three nominees receiving the most “FOR” votes (from the votes of shares present in person or represented by proxy and entitled to vote on the election of directors) will be elected. Broker non-votes will not be counted towards the vote total for Proposal No. 4.

Votes will be counted by the inspector of election appointed for the Annual Meeting, who will separately count “FOR,” “AGAINST” and “WITHHOLD” votes, abstentions and broker non-votes. “WITHHOLD” votes with respect to the election of one or more nominees for director pursuant to Proposal No. 4 will not be voted with respect to the director or directors indicated, although they will be counted for purposes of determining the presence of a quorum for the transaction of business at the Annual Meeting. Abstentions and broker non-votes will also be treated as shares present for the purpose of determining the presence of a quorum for the transaction of business at the Annual Meeting. Abstentions and broker non-votes will not, however, be considered votes cast at the Annual Meeting and will therefore not have any effect with respect to Proposal Nos. 5, 6, 7 and 8. Abstentions and broker non-votes will have the same effect as “AGAINST” votes for Proposal Nos. 2 and 3.

As of June 13, 2022, the directors and executive officers of Caladrius beneficially owned approximately 1.8% of the outstanding shares of Caladrius Common Stock entitled to vote at the Annual Meeting. As of June 13, 2022, Caladrius is not aware of any affiliate of Cend owning any shares of Caladrius Common Stock entitled to vote at the Annual Meeting.

For a more complete description of what Cend Stockholders and holders of Cend Options will receive in the Merger, please see the section entitled “The Merger—Merger Consideration and Adjustment” in this proxy statement/prospectus/information statement.

If the Merger is not treated as a reorganization under Section 368(a) of the Code, then, subject to the limitations and qualifications described in the section entitled “The Merger—Material U.S. Federal Income Tax Consequences of the Merger” in this proxy statement/prospectus/information statement, each Cend Stockholder will generally recognize gain or loss, for U.S. federal income tax purposes, on the receipt of shares of Caladrius Common Stock issued to such Cend Stockholder and on any cash received in lieu of fractional shares in connection with the Merger. The tax consequences to each Cend Stockholder will depend on that stockholder’s particular circumstances. Each Cend Stockholder should consult with his, her or its tax advisor for a full understanding of the tax consequences of the Merger to that stockholder.

If, at the close of business on the Record Date, your shares of Caladrius Common Stock were registered directly in your name with Caladrius’ transfer agent, Continental Stock Transfer & Trust Company, then you are a Caladrius Stockholder of record. As a Caladrius Stockholder of record, you may vote virtually at the Annual Meeting or vote by proxy. Whether or not you plan to attend the Annual Meeting, please vote as soon as possible by completing and returning the enclosed proxy card or vote by proxy over the telephone or on the internet as instructed below to ensure your vote is counted.

If, at the close of business on the Record Date, your shares of Caladrius Common Stock were not held in your name, but rather in an account at a brokerage firm, bank, dealer or other similar organization, then you are the beneficial owner of shares held in “street name” and these proxy materials are being forwarded to you by that organization. The organization holding your account is considered to be the stockholder of record for purposes of voting at the Annual Meeting. As a beneficial owner, you have the right to direct your broker or other agent how to vote the shares in your account. You are also invited to attend the Annual Meeting. However, because you are not the stockholder of record, you may not vote your shares in person at the Annual Meeting unless you request and obtain a valid proxy from your broker or other agent.

Abstentions and broker non-votes (as described below) will be counted towards the quorum requirement. If there is no quorum, the holders of a majority of shares present and entitled to vote at the meeting in person or represented by proxy may adjourn the Annual Meeting to another date.

anticipated to be “non-routine” matters, but Proposal No. 2 regarding the Reverse Stock Split and Proposal No. 5 regarding the ratification of the selection of the independent registered public accounting firm are anticipated to be “routine” matters. Broker non-votes will not be counted toward the vote total for any proposal at the Annual Meeting.

If you wish to submit a proposal before the stockholders or nominate a director at the 2023 annual meeting of Caladrius Stockholders, but you are not requesting that your proposal or nomination be included in the proxy materials for that meeting, then you must follow the procedures set forth in Caladrius’ bylaws and, among other things, notify Caladrius’ Corporate Secretary in writing between    , 2023 and    , 2023. However, if the date of the 2023 annual meeting of Caladrius Stockholders is more than 30 days before or more than 60 days after    , 2023, then you must give notice no later than the 90th day prior to that meeting or, if later, the 10th day following the day on which public disclosure of that annual meeting date is first made. You are also advised to review Caladrius’ bylaws, which contain additional requirements regarding advance notice of stockholder proposals and director nominations.

If you are a Caladrius Stockholder of record, you may provide your proxy instructions in one of two different ways. First, you can mail your signed proxy card in the enclosed return envelope. You may also provide your proxy instructions via telephone or via the Internet by following the instructions on your proxy card or voting instruction form. Please provide your proxy instructions only once, unless you are revoking a previously delivered proxy instruction, and as soon as possible so that your shares can be voted at the Annual Meeting.

If you are a Cend Stockholder, you may execute and return your written consent to Cend in accordance with the instructions provided.

If your shares of Caladrius stock are registered directly in your name with our transfer agent, you are considered, with respect to those shares, to be the “stockholder of record,” and the proxy materials and proxy card are being sent directly to you by Caladrius. There are four methods by which you may vote your shares at the Annual Meeting:

The Annual Meeting will be a virtual meeting of stockholders conducted via a live webcast that provides stockholders the same rights and opportunities to participate as they would have at an in-person meeting. We believe that a virtual meeting will provide expanded stockholder access and participation and improved communications. You will be able to vote your shares electronically at the virtual meeting. To attend and submit your questions during the virtual meeting, please visit www.virtualshareholdermeeting.com/CLBS2022SM. To participate and vote during the Annual Meeting, you will need the 16-digit control number included on your Internet Notice or on your proxy card. Beneficial shareholders who do not have a control number may gain access to and vote at the meeting by logging in to their broker, brokerage firm, bank or other nominee’s website and selecting the stockholder communications mailbox to access the meeting; instructions should also be provided on the voting instruction card provided by your broker, bank, or other nominee. If you encounter any difficulties accessing the virtual meeting during check-in or the meeting, please call the technical support number that will be posted on the virtual shareholder meeting log-in page.

Caladrius Biosciences, Inc.

110 Allen Road, 2^nd Floor

Basking Ridge, New Jersey 07920

Tel: (908) 842-0100

Attn: David J. Mazzo, Ph.D., President and Chief Executive Officer

If you are a Cend Stockholder, and would like additional copies, without charge, of this proxy statement/prospectus/information statement or if you have questions about the Merger, including the procedures for voting your shares, you should contact:

Cend Therapeutics, Inc.

12544 High Bluff Drive, Suite 400

San Diego, California 92130

Tel: (858) 795-5123

Attn: David Slack, President and Chief Executive Officer

The combined organization will be faced with a market environment that cannot be predicted and that involves significant risks, many of which will be beyond its control. In addition to the other information contained in this proxy statement/prospectus/information statement, you should carefully consider the material risks described below before deciding how to vote your shares of stock. In addition, you should read and consider the risks associated with the business of Caladrius because these risks may also affect the combined organization—these risks can be found in Caladrius’ Annual Report on Form 10-K, as updated by subsequent Quarterly Reports on Form 10-Q, all of which are filed with the SEC and incorporated by reference into this proxy statement/prospectus/information statement. You should also read and consider the other information in this proxy statement/prospectus/information statement and the other documents incorporated by reference into this proxy statement/prospectus/information statement. Please see the section entitled “Where You Can Find More Information” in this proxy statement/prospectus/information statement.

The Merger Agreement has set the Exchange Ratio formula for Cend Capital Stock, and the Exchange Ratio is adjustable upward or downward based on Caladrius’ net cash and Cend’s unpaid transaction costs at the closing of the Merger and changes in the outstanding Cend Capital Stock or the outstanding Caladrius Common Stock, including in connection with the proposed Reverse Stock Split prior to completion of the Merger as described in the section entitled “The Merger—Merger Consideration and Adjustment” in this proxy statement/prospectus/information statement. Any changes in the market price of Caladrius Common Stock before the completion of the Merger will not affect the number of shares Cend Stockholders will be entitled to receive pursuant to the Merger Agreement. Therefore, if before the completion of the Merger, the market price of Caladrius Common Stock declines from the market price on the date of the Merger Agreement, then Cend Stockholders could receive merger consideration with substantially lower value. Similarly, if before the completion of the Merger, the market price of Caladrius Common Stock increases from the market price on the date of the Merger Agreement, then Cend Stockholders could receive merger consideration with substantially more value for their shares of Cend Capital Stock than the parties had negotiated in the establishment of the Exchange Ratio. The Merger Agreement does not include a price-based termination right. Because the Exchange Ratio does not adjust as a result of changes in the value of Caladrius Common Stock, for each one percentage point that the market value of Caladrius Common Stock rises or declines, there is a corresponding one percentage point rise or decline, respectively, in the value of the total merger consideration issued to Cend Stockholders.

For purposes of the Merger Agreement, cash is subject to certain reductions, including, without limitation, accounts payable, accrued expenses (except those related to the Merger), current liabilities payable in cash, unpaid expenses related to the Merger and certain other unpaid obligations, including declared but unpaid dividends. In the event the amount of Caladrius’ cash is smaller or such reductions are greater than anticipated, Caladrius Stockholders could hold a significantly smaller portion of the combined organization. Additionally, the Merger Agreement includes a closing condition based upon a minimum net cash balance depending on when the closing of the Merger occurs. In the event that Caladrius’ net cash falls below this threshold, Cend would not be obligated to consummate the Merger.

In the event the amount of Cend’s unpaid transaction costs exceed $250,000, Cend Stockholders could hold a significantly smaller portion of the combined organization. In addition, the provisions of the Merger Agreement

providing for a reduction in the ownership of Caladrius Stockholders for cash shortfalls also provide for an increase in the ownership of Caladrius Stockholders in the even the amount of Caladrius’ cash is greater than certain other thresholds. These factors could combine to materially reduce the Cend Stockholders’ ownership of the combined organization.

If the Merger is not completed, Caladrius and Cend are subject to the following risks:

In addition, if the Merger Agreement is terminated and the Caladrius Board of Directors or the Cend Board of Directors determines to seek another business combination, there can be no assurance that either Caladrius or Cend will be able to find a partner willing to provide equivalent or more attractive consideration than the consideration to be provided by each party in the Merger.

In general, either Caladrius or Cend can refuse to complete the Merger if there is a material adverse change affecting the other party between the date of the Merger Agreement, and the Closing. However, certain types of changes do not permit either party to refuse to complete the Merger, even if such change could be said to have a material adverse effect on Caladrius or Cend, including:

If adverse changes occur and Caladrius and Cend still complete the Merger, the price of Caladrius Common Stock may suffer. This in turn may reduce the value of the Merger to the Caladrius Stockholders, the Cend Stockholders or both.

Certain officers and directors of Caladrius and Cend participate in arrangements that provide them with interests in the Merger that are different from yours, including, among others, the continued service as an officer or director of the combined organization, severance benefits, continued indemnification and the potential ability to sell an increased number of shares of common stock of the combined organization in accordance with Rule 144 under the Securities Act of 1933, as amended (the “Securities Act”). For example, Caladrius has entered into certain employment and severance benefits agreements with each of its current executive officers that may result in the receipt by such executive officers of cash severance payments and other benefits with a total value of approximately $3.0 million (collectively, not individually), based on data available as of June 13, 2022 and assuming a covered termination of employment of each executive officer’s employment as of such date. For more information concerning the treatment of Caladrius options in connection with the Merger, see the section entitled “The Merger Agreement—Treatment of Caladrius Options” in this proxy statement/prospectus/information statement. In addition, and for example, certain of Cend’s directors and executive officers have options, subject to vesting (with acceleration of vesting triggered by the Merger in some instances), to purchase shares of Cend Common Stock which, at the Closing, shall be converted into and become options to purchase shares of Caladrius Common Stock; certain of Cend’s directors and executive officers are expected to become directors and executive officers of Caladrius upon the Closing; and all of Cend’s directors and executive officers are entitled to certain indemnification and liability insurance coverage pursuant to the terms of the Merger Agreement. For more information concerning the interests of Caladrius and Cend executive officers and directors, see the sections entitled “The Merger—Interests of the Caladrius Directors and Executive Officers in the Merger” and “The Merger—Interests of the Cend Directors and Executive Officers in the Merger” in this proxy statement/prospectus/information statement.

The market price of Caladrius Common Stock may decline as a result of the Merger for a number of reasons if:

If the combined organization is unable to realize the full strategic and financial benefits currently anticipated from the Merger, Caladrius Stockholders will have experienced substantial dilution of their ownership interests without receiving any commensurate benefit, or only receiving part of the commensurate benefit, and likewise the value of the shares in the combined organization received by Cend Stockholders may be of significantly less value than anticipated, to the extent the combined organization is able to realize only part of the strategic and financial benefits currently anticipated from the Merger.

After the completion of the Merger, the current Caladrius Stockholders and Cend Stockholders will own a smaller percentage of the combined organization than their ownership of their respective companies prior to the Merger. Immediately after the Merger, Caladrius Stockholders, whose shares of Caladrius Common Stock will remain outstanding after the Merger, will own approximately 50% of the outstanding Caladrius Common Stock and Cend Stockholders will own approximately 50% of the outstanding Caladrius Common Stock, in each case, excluding securities convertible or exercisable into shares of Caladrius Common Stock. These estimates are based on the anticipated Exchange Ratio and are subject to adjustment.

Covenants in the Merger Agreement impede the ability of Caladrius and Cend to make acquisitions, subject to certain exceptions relating to fiduciary duties, as set forth below, or to complete other transactions that are not in the ordinary course of business pending completion of the Merger. As a result, if the Merger is not completed, the parties may be at a disadvantage to their competitors during such period. In addition, while the Merger Agreement is in effect, each party is generally prohibited from soliciting, initiating, encouraging or entering into certain extraordinary transactions, such as merger, sale of assets or other business combination outside the ordinary course of business with any third party, subject to certain exceptions relating to fiduciary duties, as set forth below. Any such transactions could be favorable to such party’s stockholders.

The terms of the Merger Agreement prohibit each of Caladrius and Cend from soliciting alternative takeover proposals or cooperating with persons making unsolicited takeover proposals, except in limited circumstances when such party’s board of directors determines in good faith that an unsolicited alternative takeover proposal is or is reasonably likely to be inconsistent with the board’s fiduciary duties. Moreover, even if a party receives what the party’s board of directors determine is a superior proposal, the Merger Agreement does not permit either party to terminate the Merger Agreement to enter into a superior proposal.

The outstanding Cend Capital Stock is privately held and is not traded in any public market. The lack of a public market makes it extremely difficult to determine the fair market value of Cend Capital Stock. Because the percentage of Caladrius equity to be issued to Cend Stockholders was determined based on negotiations between the parties, it is possible that the value of the Caladrius Common Stock to be received by Cend Stockholders will be less than the fair market value of Cend Capital Stock, or Caladrius may pay more than the aggregate fair market value of Cend Capital Stock.

Even if the Merger is approved by Caladrius Stockholders and Cend Stockholders, specified conditions must be satisfied or waived to complete the Merger. These conditions are set forth in the Merger Agreement and described in the section entitled “The Merger Agreement—Conditions to the Completion of the Merger” in this proxy statement/prospectus/information statement. Caladrius and Cend cannot assure you that all of the conditions will be satisfied or waived. If the conditions are not satisfied or waived, the Merger will not occur or will be delayed, and Caladrius and Cend each may lose some or all of the intended benefits of the Merger.

Caladrius and Cend intend for the Merger to qualify as a reorganization within the meaning of Section 368(a) of the Code, as described in the section entitled “The Merger—Material U.S. Federal Income Tax Consequences of the Merger” in this proxy statement/prospectus/information statement. In the event that the Merger does not

qualify as a reorganization, the Merger would result in taxable gain or loss for each Cend Stockholder, with the amount of such gain or loss determined by the amount that each Cend Stockholder’s adjusted tax basis in the Cend Capital Stock surrendered is less or more than the fair market value of the Caladrius Common Stock and any cash in lieu of a fractional share received in exchange therefor. Each holder of Cend Capital Stock is urged to consult with his, her or its own tax advisor with respect to the tax consequences of the Merger.

The principal purpose of the proposed Reverse Stock Split is to increase the per-share market price of Caladrius Common Stock. It cannot be assured, however, that the proposed Reverse Stock Split will accomplish this objective for any meaningful period of time. While it is expected that the reduction in the number of outstanding shares of Caladrius Common Stock will proportionally increase the market price of Caladrius Common Stock, it cannot be assured that the proposed Reverse Stock Split will increase the market price of Caladrius Common Stock by a multiple of the proposed Reverse Stock Split ratio, or result in any permanent or sustained increase in the market price of Caladrius Common Stock, which is dependent upon many factors, including the combined organization’s business and financial performance, general market conditions and prospects for future success. Thus, while the stock price of the combined organization might meet the continued listing requirements for The Nasdaq Capital Market initially, it cannot be assured that it will continue to do so.

Although the Caladrius Board of Directors believes that the anticipated increase in the market price of the combined organization’s common stock could encourage interest in its common stock and possibly promote greater liquidity for its stockholders, such liquidity could also be adversely affected by the reduced number of shares outstanding after the proposed Reverse Stock Split. The reduction in the number of outstanding shares may lead to reduced trading and a smaller number of market makers for Caladrius Common Stock.

Should the market price of the combined organization’s common stock decline after the proposed Reverse Stock Split, the percentage decline may be greater, due to the smaller number of shares outstanding, than it would have been prior to the proposed Reverse Stock Split. A reverse stock split may be viewed negatively by the market and, consequently, can lead to a decrease in the combined organization’s overall market capitalization. If the per share market price does not increase in proportion to the proposed Reverse Stock Split ratio, then the value of the combined organization, as measured by its stock capitalization, will be reduced. In some cases, the per-share stock price of companies that have effected reverse stock splits subsequently declined back to pre-reverse split levels, and accordingly, it cannot be assured that the total market value of Caladrius Common Stock will remain the same after the proposed Reverse Stock Split is effected, or that the proposed Reverse Stock Split will not have an adverse effect on the stock price of Caladrius Common Stock due to the reduced number of shares outstanding after the proposed Reverse Stock Split.

Caladrius has a limited operating history, limited capital, and limited sources of revenue. Since Caladrius’ inception in 1980 through December 31, 2021, Caladrius has incurred aggregate net losses of approximately $453.0 million. Caladrius’ net losses from continuing operations attributable to common stockholders for the years ended December 31, 2021 and December 31, 2020 were approximately $27.5 million and $8.2 million, respectively. As of December 31, 2021, Caladrius’ cash and cash equivalents and marketable securities were $95.0 million. Caladrius’ current business has not generated revenues in the past and for the foreseeable future it does not expect it to generate revenue to be sufficient to cover costs attributable to that business or to Caladrius’

operations as a whole, including Caladrius’ development activities associated with our product candidates. Ultimately, Caladrius may never generate sufficient revenue from its business to reach profitability, generate positive cash flow or sustain, on an ongoing basis, its current or projected levels of product development and other operations.

Caladrius’ current operating plan will require significant levels of additional capital to fund the continued development of its cell therapy product candidates and its clinical development activities.

Caladrius’ clinical activities are expected to continue to grow as its programs are advanced and they will require significant investment over a period of several years before they could potentially be approved by the U.S. Food and Drug Administration (“FDA”) and commercialized by it or a partner, if ever. Even if data from Caladrius’ current clinical trials for its product candidates were deemed positive, it may be required to conduct additional clinical trials of the product candidates, including larger and more expensive pivotal Phase 3 trials, to pursue commercialization of the candidates. To do so, Caladrius will need to raise additional capital, enter into collaboration agreements with third parties or undertake any combination thereof. If Caladrius is unsuccessful in its efforts to raise capital or find collaborative partners, it will likely need to otherwise delay or abandon the trials.

The amount and timing of Caladrius’ future capital requirements also will likely depend on many other factors, including:

To both fund our clinical trials and support Caladrius’ future operations, it would likely seek to raise capital through a variety of different public and/or private financings vehicles. This could include, but not be limited to, utilization of Caladrius’ at-the-market (“ATM”) offering agreement with H.C. Wainwright & Co., LLC (“HCW”) potential issuances of other debt or equity securities in public or private financings and/or sale or licensing of assets. If Caladrius raises capital through the sale of equity, or securities convertible into equity, it will result in dilution to our then-existing stockholders. Servicing the interest and principal repayment obligations under debt Caladrius incurs, or whether any such debt is called, would divert funds that might otherwise be available to support research and development, clinical or commercialization activities. In addition, debt financing involves covenants that restrict Caladrius’ ability to operate its business. In certain cases, Caladrius also may seek funding through collaborative arrangements that would likely require it to relinquish certain rights to its technology or product candidates and diminish its share in the future revenues associated with the partnered product.

Ultimately, Caladrius may be unable to raise capital or enter into collaborative relationships on terms that are acceptable to it, if at all. Caladrius’ inability to obtain necessary capital or financing to fund our future operating needs could adversely affect its business, results of operations and financial condition.

Caladrius has no products approved for commercial sale, has not generated any revenue from product sales, and does not anticipate generating any revenue from product sales until sometime after it has received regulatory approval for the commercial sale of a product candidate, which may never occur. Caladrius’ ability to generate revenue from product sales and achieve profitability depends significantly on its success in many factors, including:

Even if one or more of the product candidates that Caladrius develops is approved for commercial sale, it anticipates incurring significant costs associated with commercializing any approved product candidate. Caladrius’ expenses could increase beyond expectations if we are required by the FDA, or other regulatory agencies, domestic or foreign, to change its manufacturing processes or assays, or to perform clinical, nonclinical, or other types of studies in addition to those that it currently anticipates. If Caladrius is successful in obtaining regulatory approvals to market one or more of its product candidates, its revenue will depend, in part, upon the size of the markets in the territories for which it obtains regulatory approval, the accepted price for the product, the ability to receive reimbursement at any price, and whether it owns the commercial rights for that territory. If the number of Caladrius’ addressable disease patients is not as significant as it estimates, the indication approved by regulatory authorities is narrower than it expects, or the reasonably accepted population for treatment is narrowed by competition, physician choice or treatment guidelines, it may not generate significant revenue from sales of such products, even if approved. If Caladrius is not able to generate revenue from the sale of any approved products, it may never become profitable.

Section 404(b) of the Sarbanes-Oxley Act of 2002 requires an independent registered public accounting firm to test the internal control over financial reporting of public companies, and to report on the effectiveness of such controls, for each fiscal year ending after June 15, 2010. Under the Dodd Frank Wall Street Reform and

Consumer Protection Act of 2010 (the “Dodd Frank Act”), Caladrius is exempt from Section 404(b) as long as it remains a smaller reporting company or a non-accelerated filer. If Caladrius’ status as a smaller reporting company changes, it may be required to comply with this auditor attestation requirement.

In addition, Caladrius may in the future discover areas of its internal controls that need improvement, particularly with respect to businesses that it may acquire. If so, we cannot be certain that any remedial measure Caladrius takes will ensure that it have adequate internal controls over its financial processes and reporting in the future. Any failure to implement required new or improved controls, or difficulties encountered in their implementation could harm Caladrius’ operating results or cause it to fail to meet its reporting obligations. If Caladrius is unable to conclude that it has effective internal controls over financial reporting, or if it becomes necessary for its independent registered public accounting firm to provide it with an unqualified report regarding the effectiveness of our internal control over financial reporting and it is unable to do so, investors could lose confidence in the reliability of its financial statements. This could result in a decrease in the value of Caladrius Common Stock.

Caladrius is dependent upon the successful development, approval and commercialization of its product candidates. Before Caladrius is able to seek regulatory approval of its product candidates, it must conduct and complete extensive clinical trials to demonstrate their safety and efficacy in humans. Caladrius has never taken a product through the regulatory approval process or successfully to U.S. or international commercialization.

In early 2018, Caladrius treated the first patient in a clinical trial in Japan for HONEDRA® for use in CLI taking advantage of the paradigm of potential conditional approval for regenerative medicine products established by new regulations in Japan for products that show sufficient safety evidence and some evidence of efficacy. Because of difficulty enrolling the remaining patients in the trial and the costs of continued delays in such, Caladrius suspended enrollment of the trial at the end of 2021 and commenced talks with development partners as well as with Japan’s Pharmaceuticals and Medical Devices Agency (“PMDA”) to consider paths forward. There can be no assurance that Caladrius will find a partner or that PMDA will consider the drug for approval without completing enrollment of the trial, such that HONEDRA® may be delayed indefinitely or never commercialized.

In late 2020 Caladrius began enrolling patients in the FREEDOM Trial using CD34+ cells to treat CMD (CLBS16). That trial also has been delayed significantly by COVID-19-related challenges to enrollment and supply chain issues. Additionally, Caladrius currently has an open investigational new drug application (“IND”) for CLBS201 in a pilot study examining the effectiveness of CD34+ cells to treat diabetic kidney disease.

Clinical testing is expensive, difficult to design and implement, and can take many years to complete. Importantly, a failure of one or more of these or any other clinical trials can occur at any stage of testing. Caladrius may experience numerous unforeseen events during, or as a result of clinical trials that could delay or prevent its ability to complete its clinical trials, receive regulatory approval or commercialize its cell therapy product candidates, including the following: