As filed with the U.S. Securities and Exchange Commission on March 16, 2020

Registration No. 333-234627

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Amendment No. 1

to

FORM S-4

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

Lantheus Holdings, Inc.

(Exact name of registrant as specified in its charter)

331 Treble Cove Road, North Billerica, Massachusetts 01862

(978) 671-8001

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Michael P. Duffy

Senior Vice President and General Counsel

331 Treble Cove Road, Building 600-2

North Billerica, Massachusetts 01862

(978) 671-8408

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies of all communications, including communications sent to agent for service, should be sent to:

Approximate date of commencement of proposed sale to the public: As soon as practicable after the effective date of this registration statement and upon completion of the merger described in the enclosed joint proxy statement/prospectus.

If the securities being registered on this form are being offered in connection with the formation of a holding company and there is compliance with General Instruction G, check the following box.  ☐

If this form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act of 1933, as amended (the “Securities Act”), check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

If this form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering.  ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”).

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act.  ☐

If applicable, place an X in the box to designate the appropriate rule provision relied upon in conducting this transaction:

Exchange Act Rule 13e-4(i) (Cross-Border Issuer Tender Offer)  ☐

Exchange Act Rule 14d-l(d) (Cross-Border Third-Party Tender Offer)  ☐

CALCULATION OF REGISTRATION FEE

The Registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the registration statement shall become effective on such date as the Securities and Exchange Commission, acting pursuant to Section 8(a), may determine.

Information contained herein is subject to completion or amendment. A registration statement relating to these securities has been filed with the U.S. Securities and Exchange Commission. These securities may not be sold nor may offers to buy be accepted prior to the time the registration statement becomes effective. This joint proxy statement/prospectus shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any jurisdiction in which such offer, solicitation or sale is not permissible.

PRELIMINARY—SUBJECT TO COMPLETION—DATED MARCH 16, 2020

MERGER PROPOSAL—YOUR VOTE IS VERY IMPORTANT

March 16, 2020

Dear Stockholders:

On behalf of the boards of directors of Lantheus Holdings, Inc. (“Lantheus Holdings”) and Progenics Pharmaceuticals, Inc. (“Progenics”), we are pleased to enclose the joint proxy statement/prospectus relating to the merger of Progenics with a wholly-owned subsidiary of Lantheus Holdings (the “merger”) pursuant to the terms of an amended and restated merger agreement entered into by Lantheus Holdings and Progenics on February 20, 2020, (as it may be further amended from time to time, the “merger agreement”).

If the merger is completed, Progenics stockholders immediately prior to the completion of the merger will be entitled to receive for each share of Progenics common stock held by them (i) 0.31 of a share of Lantheus Holdings common stock and (ii) one contingent value right representing the right to receive such stockholder’s pro rata share of aggregate cash payments equal to 40% of U.S. net sales generated by PyL^TM (¹⁸F-DCFPyL), Progenics’ prostate-specific membrane antigen targeted imaging agent designed to visualize prostate cancer currently in late stage clinical development, in calendar years 2022 and 2023 in excess of $100 million and $150 million, respectively, subject to and in accordance with the terms of the Contingent Value Rights Agreement, including the aggregate payment cap specified therein, as described in more detail in the accompanying joint proxy statement/prospectus under the heading “The Merger Agreement—Merger Consideration.” The exchange ratio is fixed and will not be adjusted to reflect stock price changes prior to the completion of the merger. Based on the closing price of shares of Lantheus Holdings common stock on March 13, 2020, the most recent trading day prior to the date of the accompanying joint proxy statement/prospectus for which this information was available, the stock consideration represented approximately $4.01 in value per share of Progenics common stock. The value of the stock consideration to be received by Progenics stockholders will fluctuate with changes in the price of the shares of Lantheus Holdings common stock. We urge you to obtain current market quotations for shares of Lantheus Holdings common stock and shares of Progenics common stock. Shares of Lantheus Holdings common stock are traded on the Nasdaq Global Market under the symbol “LNTH” and shares of Progenics common stock are traded on the Nasdaq Stock Market under the symbol “PGNX.”

Each of Lantheus Holdings and Progenics will hold a special meeting of its stockholders in connection with the merger agreement.

The Lantheus Holdings special meeting of stockholders will be held at [●], on [●], at [●], Eastern Time. At the Lantheus Holdings special meeting, Lantheus Holdings stockholders will be asked to vote on (i) a proposal to approve the issuance of shares of Lantheus Holdings common stock in the merger and (ii) a proposal to approve the adjournment from time to time of the Lantheus Holdings special meeting if necessary to solicit additional proxies if there are not sufficient votes at the time of the Lantheus Holdings special meeting, or any adjournment or postponement thereof, to approve the issuance of shares of Lantheus Holdings common stock in the merger. Lantheus Holdings’ board of directors determined that the merger agreement and the transactions contemplated by the merger agreement, including the merger and the issuance of shares of Lantheus Holdings common stock in the merger, are advisable, fair to and in the best interests of Lantheus Holdings and its stockholders and unanimously recommends that Lantheus Holdings stockholders vote “FOR” each proposal.

The Progenics special meeting of stockholders will be held at [●], on [●], at [●], Eastern Time. At the Progenics special meeting, Progenics stockholders will be asked to vote on (i) a proposal to adopt the merger agreement, (ii) a proposal to approve the adjournment from time to time of the Progenics special meeting if necessary to solicit additional proxies if there are not sufficient votes to adopt the merger agreement at the time of the

Progenics special meeting, or any adjournment or postponement thereof, and (iii) a proposal to approve, on an advisory (non-binding) basis, the compensation that will or may be paid or provided by Progenics to its named executive officers in connection with the merger. The Progenics board of directors unanimously determined that the merger agreement and the transactions contemplated by the merger agreement, including the merger, are advisable, fair to and in the best interests of Progenics and its stockholders and unanimously recommends that Progenics stockholders vote “FOR” each proposal.

Lantheus Holdings expects to issue up to approximately 26,844,956 shares of its common stock to Progenics stockholders in the merger. In addition, shares of Lantheus Holdings common stock may be issued from time to time following the effective time of the merger to holders of options to purchase Progenics common stock on the terms set forth in the merger agreement. See “The Merger Agreement—Treatment of Progenics Stock Options” beginning on page 183 of the accompanying joint proxy statement/prospectus for a more detailed explanation. Based on the number of fully diluted shares of Lantheus Holdings common stock and Progenics common stock outstanding as of March 13, 2020, Lantheus Holdings and Progenics estimate that, immediately after the completion of the merger, Lantheus Holdings stockholders will own approximately 60% of the outstanding shares of common stock of the combined company (based on fully diluted shares outstanding) and former Progenics stockholders will own approximately 40% of the outstanding shares of common stock of the combined company (based on fully diluted shares outstanding).

The accompanying joint proxy statement/prospectus provides important information regarding the Lantheus Holdings and Progenics special meetings and a detailed description of the merger agreement, the merger, the issuance of shares of Lantheus Holdings common stock in the merger, the adjournment proposals and the proposal to approve, on an advisory (non-binding) basis, the compensation that will or may be paid or provided by Progenics to its named executive officers in connection with the merger. We urge you to read carefully and in its entirety the accompanying joint proxy statement/prospectus (including the annexes and any documents incorporated by reference into the accompanying joint proxy statement/prospectus). Please pay particular attention to the section entitled “Risk Factors” beginning on page 41 of the accompanying joint proxy statement/prospectus. You can also obtain information about Lantheus Holdings and Progenics from documents that Lantheus Holdings and Progenics previously have filed with the U.S. Securities and Exchange Commission.

For a discussion of the material U.S. federal income tax consequences of the merger, see “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Material U.S. Federal Income Tax Consequences” beginning on page 170 of the accompanying joint proxy statement/prospectus.

We hope to see you at the applicable special meeting and look forward to the successful completion of the merger.

Your vote is very important, regardless of the number of shares you own. We cannot complete the merger and the merger consideration will not be paid unless (i) Lantheus Holdings stockholders approve the issuance of shares of Lantheus Holdings common stock in the merger and (ii) Progenics stockholders adopt the merger agreement. Whether or not you plan to attend your company’s special meeting of stockholders, please submit your proxy as soon as possible to make sure your shares are represented at that meeting.

Neither the U.S. Securities and Exchange Commission nor any state securities commission has approved or disapproved of the securities to be issued under the accompanying joint proxy statement/prospectus or determined that the accompanying joint proxy statement/prospectus is accurate or complete. Any representation to the contrary is a criminal offense.

The accompanying joint proxy statement/prospectus is dated March [●], 2020 and is first being mailed to Lantheus Holdings stockholders on or about March [●], 2020 and Progenics stockholders on or about March [●], 2020.

Lantheus Holdings, Inc.

331 Treble Cove Road

North Billerica, Massachusetts 01862

(978) 671-8001

NOTICE OF SPECIAL MEETING OF STOCKHOLDERS

OF LANTHEUS HOLDINGS, INC.

TO BE HELD ON [●]

[●], EASTERN TIME

To the Stockholders of Lantheus Holdings, Inc.:

NOTICE IS HEREBY GIVEN that a special meeting of stockholders of Lantheus Holdings, Inc., a Delaware corporation, which is referred to in this notice as Lantheus Holdings, will be held at [●], on [●], at [●], Eastern Time, for the following purposes:

The Lantheus Holdings board of directors has fixed the close of business on [●] as the record date for the determination of the stockholders entitled to vote at the Lantheus Holdings special meeting or any adjournment or postponement thereof. Only stockholders of record at the record date are entitled to notice of, and to vote at, the Lantheus Holdings special meeting or any adjournment or postponement thereof.

Your vote is very important, regardless of the number of shares of Lantheus Holdings common stock that you own. Approval of the stock issuance proposal requires the affirmative vote of at least a majority of the votes cast by holders of outstanding shares of Lantheus Holdings common stock at a duly called and held meeting of Lantheus Holdings stockholders at which a quorum is present. Approval of the Lantheus Holdings adjournment proposal requires the affirmative vote of holders of a majority of the shares of Lantheus Holdings common stock present in person or represented by proxy at the Lantheus Holdings special meeting and entitled to vote thereat (assuming a quorum is present). In the absence of a quorum, the Lantheus Holdings special meeting may be adjourned by the Chairperson of the meeting.

As part of our precautions regarding the coronavirus (COVID-19), we are sensitive to the public health and travel concerns that our stockholders may have, as well as any protocols that federal, state and local governments may

impose. In the event we determine it is necessary or appropriate to take additional steps regarding how we conduct our meeting, including by holding the meeting virtually over the Internet, we will announce this decision in advance, and details will be posted on our website and filed with the SEC.

Lantheus Holdings’ board of directors determined that the merger agreement and the transactions contemplated by the merger agreement, including the merger and the issuance of shares of Lantheus Holdings common stock in the merger, are advisable, fair to and in the best interests of Lantheus Holdings and its stockholders and unanimously recommends that Lantheus Holdings stockholders vote (i) “FOR” the approval of the issuance of shares of Lantheus Holdings common stock in the merger and (ii) “FOR” the approval of the adjournment from time to time of the Lantheus Holdings special meeting if necessary to solicit additional proxies if there are not sufficient votes at the time of the Lantheus Holdings special meeting, or any adjournment or postponement thereof, to approve the issuance of shares of Lantheus Holdings common stock in the merger.

By order of the Board of Directors,

BRIAN MARKISON

Chairman of the Board of Directors

North Billerica, Massachusetts

[●], 2020

YOUR VOTE IS IMPORTANT!

WHETHER OR NOT YOU EXPECT TO ATTEND THE LANTHEUS HOLDINGS SPECIAL MEETING IN PERSON, WE URGE YOU TO SUBMIT YOUR PROXY AS PROMPTLY AS POSSIBLE (1) VIA THE INTERNET, (2) BY TELEPHONE OR (3) BY COMPLETING, SIGNING AND DATING THE ENCLOSED LANTHEUS HOLDINGS PROXY CARD AND RETURNING IT IN THE POSTAGE-PAID ENVELOPE PROVIDED.

IMPORTANT INFORMATION IF YOU PLAN TO ATTEND THE LANTHEUS HOLDINGS SPECIAL MEETING IN PERSON:

A form of photo identification will be required to enter the meeting.

You will need to provide evidence that you are a stockholder as of the close of business on the record date. This can be a copy of your proxy card or a brokerage statement showing your shares as of the close of business on the record date.

If you hold your shares of Lantheus Holdings common stock in “street name” through a broker, bank or other nominee, you will need to contact the broker, bank or other nominee that holds your shares in order to obtain a legal proxy from that broker, bank or other nominee.

You may revoke your proxy or change your vote for shares of Lantheus Holdings common stock you hold directly in your name by (i) signing another proxy card with a later date and delivering it to 331 Treble Cove Road, North Billerica, MA 01862, Attention: Investor Relations, before the date of the Lantheus Holdings special meeting (we recommend you mail your proxy by [●] to ensure timely receipt of your proxy), (ii) submitting revised votes over the Internet or by telephone before 11:59 p.m., Eastern Time, on the calendar day immediately preceding the Lantheus Holdings special meeting, or (iii) attending the Lantheus Holdings special meeting in person and voting your shares of Lantheus Holdings common stock at the Lantheus Holdings special meeting. If your shares of Lantheus Holdings common stock are held in the name of a bank, broker or other nominee, please follow the instructions on the voting instruction form furnished to you by such bank, broker or other nominee.

The accompanying joint proxy statement/prospectus contains a detailed description of the merger, the merger agreement and the other matters to be considered at the meeting. We urge you to read carefully the accompanying joint proxy statement/prospectus, including all documents incorporated by reference into the accompanying joint proxy statement/prospectus, and its annexes, in their entirety. If you have any questions concerning the merger agreement, the merger, the issuance of shares of Lantheus Holdings common stock in the merger, the Lantheus Holdings adjournment proposal, the Lantheus Holdings special meeting or the accompanying joint proxy statement/prospectus (or any other information contained therein), would like additional copies of the accompanying joint proxy statement/prospectus or need help voting your shares of Lantheus Holdings common stock, please contact:

Innisfree M&A Incorporated

501 Madison Avenue, 20^th Floor

New York, New York 10022

Telephone (Toll-Free): (877) 750-9497

International Callers: (412) 232-3651

Banks and brokers may call collect: (212) 750-5833

Progenics Pharmaceuticals, Inc.

One World Trade Center, 47^th Floor, Suite J

New York, New York 10007

(646) 975-2500

NOTICE OF SPECIAL MEETING OF STOCKHOLDERS OF

PROGENICS PHARMACEUTICALS, INC.

TO BE HELD ON [●]

AT [●], EASTERN TIME

To the Stockholders of Progenics Pharmaceuticals, Inc.:

NOTICE IS HEREBY GIVEN that a special meeting of stockholders of Progenics Pharmaceuticals, Inc., a Delaware corporation, which is referred to in this notice as Progenics, will be held at [●], on [●], at [●], Eastern Time, for the following purposes:

The holders of record of shares of Progenics common stock, par value $0.0013 per share, which are referred to in this notice as shares of Progenics common stock, at the close of business on [●] are entitled to notice of and to vote at the Progenics special meeting or any adjournment or postponement thereof. Progenics anticipates commencing its solicitation of proxies on or about [●].

Only stockholders or their proxy holders may attend the Progenics special meeting. If you are attending the Progenics special meeting in person, you will be required to register as a stockholder or proxy holder and to show valid, government-issued identification before entering Progenics special meeting.

As part of our precautions regarding the coronavirus (COVID-19), we are sensitive to the public health and travel concerns that our stockholders may have, as well as any protocols that federal, state and local governments may impose. In the event we determine it is necessary or appropriate to take additional steps regarding how we conduct our meeting, including by holding the meeting virtually over the Internet, we will announce this decision in advance, and details will be posted on our website and filed with the SEC.

Adoption of the merger agreement requires the affirmative vote, in person or by proxy, of the holders of a majority of the shares of Progenics common stock outstanding and entitled to vote thereon. If a quorum, as

defined under Progenics’ by-laws, is not present at the Progenics’ special meeting, approval of the adjournment proposal requires the affirmative vote of holders of a majority of the shares of Progenics common stock present in person or represented by proxy at the Progenics special meeting. If a quorum, as defined under Progenics’ by-laws, is present at the Progenics special meeting, approval of the Progenics adjournment proposal requires the affirmative vote of a majority of the votes cast in person or by proxy at the Progenics special meeting by holders of Progenics common stock. Approval of the proposal to approve, on an advisory (non-binding) basis, the compensation that will or may be paid or provided by Progenics to its named executive officers in connection with the merger requires the affirmative vote of a majority of the votes cast in person or by proxy at the Progenics special meeting by holders of shares of Progenics common stock (assuming a quorum, as defined under Progenics’ by-laws, is present).

Progenics’ board of directors unanimously determined that the merger agreement and the transactions contemplated by the merger agreement (including the merger) are fair to and in the best interests of Progenics and its stockholders and unanimously recommends that Progenics stockholders vote (i) “FOR” the proposal to adopt the merger agreement, (ii) “FOR” the proposal to approve the adjournment from time to time of the Progenics special meeting if necessary to solicit additional proxies if there are not sufficient votes to adopt the merger agreement at the time of the Progenics special meeting or any adjournment or postponement thereof and (iii) “FOR” the proposal to approve, on an advisory (non-binding) basis, the compensation that will or may be paid or provided by Progenics to its named executive officers in connection with the merger.

By order of the Board of Directors,

ANN MACDOUGALL

Interim Chair of the Board of Directors of Progenics New York, New York

[●], 2020

YOUR VOTE IS IMPORTANT!

WHETHER OR NOT YOU EXPECT TO ATTEND THE PROGENICS SPECIAL MEETING IN PERSON, WE URGE YOU TO SUBMIT YOUR PROXY AS PROMPTLY AS POSSIBLE (1) VIA THE INTERNET, (2) BY TELEPHONE OR (3) BY COMPLETING, SIGNING AND DATING THE ENCLOSED PROGENICS PROXY CARD AND RETURNING IT IN THE POSTAGE-PAID ENVELOPE PROVIDED. IF YOU ATTEND THE PROGENICS SPECIAL MEETING IN PERSON AND WISH TO VOTE YOUR SHARES AT THE PROGENICS SPECIAL MEETING, YOU MAY DO SO AT ANY TIME PRIOR TO THE CLOSING OF THE POLLS AT THE PROGENICS SPECIAL MEETING. You may revoke your proxy or change your vote for shares of Progenics common stock you hold directly in your name by (i) signing another proxy card with a later date and delivering it to MacKenzie Partners, Inc., 1407 Broadway, 27th Floor, New York, New York 10018 or Progenics Pharmaceuticals, Inc., One World Trade Center, 47th Floor, Suite J, New York, New York 10007, before the date of the Progenics special meeting (we recommend you mail your proxy by [●] to ensure timely receipt of your proxy), (ii) submitting revised votes over the Internet or by telephone before 11:59 p.m., Eastern Time, on the calendar day immediately preceding the Progenics special meeting, or (iii) attending the Progenics special meeting in person and voting your shares of Progenics common stock at the Progenics special meeting. If your shares of Progenics common stock are held in the name of a bank, broker or other nominee, please follow the instructions on the voting instruction form furnished to you by bank, broker or other nominee.

Progenics cannot complete the merger and the merger consideration will not be paid unless its stockholders adopt the merger agreement and the other closing conditions specified in the merger agreement are met. Because adoption of the merger agreement requires the affirmative vote of the holders of at least a majority of the shares of Progenics common stock outstanding and entitled to vote thereon, a Progenics stockholder’s abstention from voting, the failure of a Progenics stockholder who holds his or her shares in “street name” through a broker, bank or other nominee to give voting instructions to that broker, bank or other nominee or any other failure of a Progenics stockholder to vote will have the same effect as a vote “AGAINST” the proposal to adopt the merger agreement.

We urge you to read carefully the accompanying joint proxy statement/prospectus, including all documents incorporated by reference into the accompanying joint proxy statement/prospectus, and its annexes, in their entirety. If you have any questions concerning the merger agreement, the merger, the vote on the merger agreement, the adjournment proposal, the advisory (non-binding) proposal to approve the compensation that will or may be paid or provided by Progenics to its named executive officers in connection with the merger, the Progenics special meeting or the accompanying joint proxy statement/prospectus (or any other information contained therein), would like additional copies of the accompanying joint proxy statement/prospectus or need help voting your shares of Progenics common stock, please contact:

MacKenzie Partners, Inc.

1407 Broadway, 27^th Floor

New York, New York 10018

(212) 929-5500 or (800) 322-2885

Email: pgnx@mackenziepartners.com

REFERENCES TO ADDITIONAL INFORMATION

The accompanying document is the proxy statement of Lantheus Holdings for its special meeting of stockholders, the proxy statement of Progenics for its special meeting of stockholders and the prospectus of Lantheus Holdings for the shares of its common stock to be issued in the merger. The accompanying joint proxy statement/prospectus incorporates by reference important business and financial information about Lantheus Holdings and Progenics from documents that are not included in or delivered with the accompanying joint proxy statement/prospectus. You can obtain the documents that are incorporated by reference into the accompanying joint proxy statement/prospectus (other than certain exhibits or schedules to those documents), without charge, by requesting them in writing or by telephone from Lantheus Holdings or Progenics, respectively, at the following addresses and telephone numbers, or through the U.S. Securities and Exchange Commission website at www.sec.gov:

In addition, if you have questions about the merger or the accompanying joint proxy statement/prospectus, would like additional copies of the accompanying joint proxy statement/prospectus, or need to obtain proxy cards or other information related to the proxy solicitation, please contact Innisfree M&A Incorporated, the proxy solicitor for Lantheus Holdings, toll-free at (877) 750-9497 or (412) 232-3651 for international callers, if you are a Lantheus Holdings stockholder, or MacKenzie Partners, Inc., the proxy solicitor for Progenics, toll-free at (800) 322-2885, collect at (212) 929-5500 or pgnx@mackenziepartners.com, if you are a Progenics stockholder. You will not be charged for any of these documents that you request.

To obtain timely delivery of the documents, you must request them no later than the dates specified in this joint proxy statement/prospectus. If you are a Lantheus Holdings stockholder and would like to request documents from Lantheus Holdings, please contact Innisfree M&A Incorporated by [●] in order to receive them before the Lantheus Holdings special meeting. If you are a Progenics stockholder and would like to request documents from Progenics, please contact MacKenzie Partners, Inc. by [●] in order to receive them before the Progenics special meeting.

See “Where You Can Find More Information” beginning on page 260 of the accompanying joint proxy statement/prospectus for further information.

TABLE OF CONTENTS

(i)

(ii)

(iii)

(iv)

QUESTIONS AND ANSWERS ABOUT THE MERGER AND THE SPECIAL MEETINGS

The following are some questions that you, as a stockholder of Lantheus Holdings, Inc., which is referred to in this joint proxy statement/prospectus as Lantheus Holdings, or a stockholder of Progenics Pharmaceuticals, Inc., which is referred to in this joint proxy statement/prospectus as Progenics, may have regarding the merger agreement, the merger, the stock issuance, the Lantheus Holdings adjournment proposal, the Progenics adjournment proposal, the Progenics compensation advisory proposal and the special meetings as well as brief answers to those questions. You are urged to read carefully this joint proxy statement/prospectus, including all documents incorporated by reference into this joint proxy statement/prospectus, and its annexes, in their entirety because this section may not provide all of the information that is important to you with respect to the merger agreement, the merger, the stock issuance, the Lantheus Holdings adjournment proposal, the Progenics adjournment proposal, the Progenics compensation advisory proposal and the special meetings. Additional important information is contained in the annexes to, and the documents incorporated by reference into, this joint proxy statement/prospectus. See “Where You Can Find More Information” beginning on page 260 of this joint proxy statement/prospectus.

About the Merger Agreement and the Merger

Lantheus Holdings is holding a special meeting of stockholders, which is referred to in this joint proxy statement/prospectus as the Lantheus Holdings special meeting, in order to obtain the stockholder approval necessary to approve the stock issuance, which is referred to in this joint proxy statement/prospectus as the stock issuance proposal. Approval of the stock issuance proposal requires the affirmative vote of at least a majority of the votes cast by holders of outstanding shares of Lantheus Holdings common stock, at a duly called and held meeting of Lantheus Holdings stockholders at which a quorum is present. A majority of the votes cast means that the number of votes cast “FOR” the stock issuance proposal must exceed the number of votes cast “AGAINST.” Lantheus Holdings stockholders will also be asked to approve the adjournment from time to time of the Lantheus Holdings special meeting if necessary to solicit additional proxies if there are not sufficient votes at the time of the Lantheus Holdings special meeting, or any adjournment or postponement thereof, to approve the stock issuance, which is referred to in this joint proxy statement/prospectus as the Lantheus Holdings adjournment proposal. Approval of the Lantheus Holdings adjournment proposal requires the affirmative vote of the holders of a majority of the shares present in person or represented by proxy at the Lantheus Holdings special meeting and entitled to vote thereat (assuming a quorum is present). In the absence of a quorum, the Lantheus Holdings special meeting may be adjourned by the Chairperson of the meeting. For purposes of this

1

proposal, “shares of Lantheus Holdings common stock present or represented by proxy” consist of shares voted “FOR” or “AGAINST” as well as elections to abstain from voting on the proposal. It is important that Lantheus Holdings stockholders vote their shares of Lantheus Holdings common stock on each of these matters, regardless of the number of shares owned.

Progenics is holding a special meeting of stockholders, which is referred to in this joint proxy statement/prospectus as the Progenics special meeting, in order to obtain the stockholder approval necessary to adopt the merger agreement. Adoption of the merger agreement requires the affirmative vote of the holders of a majority of the outstanding shares of Progenics common stock entitled to vote thereon. A Progenics stockholder’s abstention from voting or failure to vote will have the same effect as a vote “AGAINST” the proposal. Progenics stockholders will also be asked to approve the adjournment from time to time of the Progenics special meeting if necessary to solicit additional proxies if there are not sufficient votes to adopt the merger agreement at the time of the Progenics special meeting, or any adjournment or postponement thereof, which is referred to in this joint proxy statement/prospectus as the Progenics adjournment proposal, and to approve, on an advisory (non-binding) basis, the compensation that will or may be paid or provided by Progenics to its named executive officers, whom are referred to in this joint proxy statement/prospectus as the named executive officers, in connection with the merger, which proposal is referred to in this joint proxy statement/prospectus as the Progenics compensation advisory proposal. The vote required to approve the Progenics adjournment proposal depends on whether or not a quorum is present at the Progenics special meeting. If a quorum is not present at the Progenics special meeting, approval of the Progenics adjournment proposal requires the affirmative vote of holders of a majority of the shares of Progenics common stock present in person or represented by proxy at the Progenics special meeting. For purposes of this proposal, if a quorum is not present, “shares of Progenics common stock present in person or represented by proxy” consist of votes “FOR” or “AGAINST” as well as elections to abstain from voting on the proposal. If a quorum is present at the Progenics special meeting, approval of the Progenics adjournment proposal requires the affirmative vote of the holders of a majority of the votes cast in person or by proxy at the Progenics special meeting. For purposes of this proposal, if a quorum is present, a “majority of the votes cast” means the number of votes cast “FOR” the proposal must exceed the number of votes cast “AGAINST” the proposal. Approval of the Progenics compensation advisory proposal requires the affirmative vote of the holders of a majority of the votes cast in person or by proxy at the Progenics special meeting. For purposes of this proposal, a majority of the votes cast means that the number of votes cast “FOR” the proposal must exceed the number of votes cast “AGAINST.” It is important that Progenics stockholders vote their shares of Progenics common stock on each of these matters, regardless of the number of shares owned.

This document is being delivered to you as both a joint proxy statement of Lantheus Holdings and Progenics and a prospectus of Lantheus Holdings in connection with the merger and the stock issuance. This document is the proxy statement by which the Lantheus Holdings board of directors, which is referred to in this joint proxy statement/prospectus as the Lantheus Holdings Board, is soliciting proxies from Lantheus Holdings stockholders to vote at the Lantheus Holdings special meeting, or at any adjournment or postponement thereof, on the approval of the stock issuance proposal and the approval of the Lantheus Holdings adjournment proposal. In addition, this document is the prospectus of Lantheus Holdings pursuant to which Lantheus Holdings will issue shares of Lantheus Holdings common stock to Progenics stockholders as part of the merger consideration, as described under “The Merger Agreement—Merger Consideration” beginning on page 180 of this joint proxy statement/prospectus. This document is also the proxy statement by which the Progenics board of directors, which is referred to in this joint proxy statement/prospectus as the Progenics Board, is soliciting proxies from Progenics stockholders to vote at the Progenics special meeting, or at any adjournment or postponement thereof, on the merger agreement proposal, the Progenics adjournment proposal and the Progenics compensation advisory proposal.

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Based on the closing price of shares of Lantheus Holdings common stock on the Nasdaq Global Market on February 19, 2020, the last trading day prior to announcement of the amended transaction between Lantheus Holdings and Progenics, the stock consideration represented approximately $5.12 in value for each share of Progenics common stock. Based on the closing price of shares of Lantheus Holdings common stock on the

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Nasdaq Global Market on March 13, 2020, the most recent trading day prior to the date of this joint proxy statement/prospectus for which this information was available, the stock consideration represented approximately $4.01 in value for each share of Progenics common stock.

Because Lantheus Holdings will issue 0.31 of a share of Lantheus Holdings common stock in exchange for each share of Progenics common stock, the value of the stock consideration will depend on the market price of shares of Lantheus Holdings common stock at the time the merger is completed. The market price of shares of Lantheus Holdings common stock when Progenics stockholders receive those shares after the merger is completed will not be known at the time of the special meetings and could be greater than, less than or the same as the market price of shares of Lantheus Holdings common stock on February 19, 2020, on the date of this joint proxy statement/prospectus or at the time of the special meetings or any adjournment or postponement thereof. Because the exchange ratio is fixed and the market price of shares of Lantheus Holdings common stock has fluctuated and will continue to fluctuate, Progenics stockholders cannot be sure of the value of the stock consideration they will receive in the merger. See “Risk Factors—Risks Related to the Merger.”

For a more detailed description of the CVRs, see the section entitled “Description of the CVRs” beginning on page 225 of this joint proxy statement/prospectus. Additionally, a form of the CVR agreement is attached as Annex B to this joint proxy statement/prospectus. Progenics stockholders are encouraged to read the entire form of CVR agreement carefully because it is the principal document governing the CVRs.

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In addition, payments under the CVRs are subject to an aggregate payment cap. The sum of (i) the aggregate amount of payments paid or payable pursuant to the CVR agreement (including any interest on such amounts paid or payable to the rights agent or any CVR holder) and (ii) the amount of any other cash or the fair market value of any property (other than Lantheus Holdings common stock or the CVRs) paid or payable to Progenics stockholders as consideration pursuant to the merger agreement will not (A) exceed 19.9% of the aggregate amount of consideration paid or payable to Progenics stockholders in the merger or (B) constitute an amount the payment of which, in the opinion of nationally recognized tax counsel, would more likely than not prevent the merger from satisfying the requirement of Section 368(a)(2)(E)(ii) of the U.S. Internal Revenue Code of 1986, as amended, which is referred to in this joint proxy statement/prospectus as the Code. Such amount is referred to in this joint proxy statement/prospectus as the CVR cap.

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For Lantheus Holdings Stockholders

The approval of the stock issuance proposal by Lantheus Holdings stockholders is a condition to the obligations of Progenics and Lantheus Holdings to complete the merger. The approval of the Lantheus Holdings adjournment proposal is not a condition to the obligations of Progenics or Lantheus Holdings to complete the merger.

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If you hold shares of Lantheus Holdings common stock directly in your name as a stockholder of record, you may vote via the Internet by accessing the website shown on your proxy card or by telephone by calling the toll-free number shown on your proxy card. In order to submit a proxy to vote via the Internet or by telephone, you will need the control number on your proxy card (which is unique to each Lantheus Holdings stockholder to ensure all voting instructions are genuine and to prevent duplicate voting). Votes may be submitted via the Internet or by telephone 24 hours a day, seven days a week, and must be received by 11:59 p.m., Eastern Time, on the calendar day immediately preceding the Lantheus Holdings special meeting. Please be aware that if you vote by telephone or over the Internet, you may incur costs such as telephone and Internet access charges for which you will be responsible.

If you hold shares of Lantheus Holdings common stock in “street name,” meaning through a broker, bank or other nominee, you may vote via the Internet or by telephone only if Internet or telephone voting is made available by your broker, bank or other nominee. Please follow the voting instructions provided by your broker, bank or other nominee with these materials.

You may vote via the Internet or by telephone until 11:59 p.m., Eastern Time, on the calendar day immediately preceding the Lantheus Holdings special meeting.

By Mail

If you hold shares of Lantheus Holdings common stock directly in your name as a stockholder of record, in order to vote by mail, you may submit a proxy card. You will need to complete, sign and date your proxy card and return it using the postage-paid return envelope provided.

If you hold shares of Lantheus Holdings common stock in “street name,” meaning through a broker, bank or other nominee, in order to provide voting instructions by mail you will need to complete, sign and date the voting instruction form provided by your broker, bank or other nominee with these materials and return it in the postage-paid return envelope provided. Your broker, bank or other nominee must receive your voting instruction form in sufficient time to vote your shares.

We recommend you mail your proxy timely to ensure receipt of your proxy before the date of the special meeting.

In Person

If you hold shares of Lantheus Holdings common stock directly in your name as a stockholder of record, you may vote in person at the Lantheus Holdings special meeting. Stockholders of record also may be represented by another person at the Lantheus Holdings special meeting by executing a proper proxy designating that person and having that proper proxy be presented to the inspector of election with the applicable ballot at the Lantheus Holdings special meeting.

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If you hold shares of Lantheus Holdings common stock in “street name,” meaning through a broker, bank or other nominee, you must obtain a written legal proxy from that broker, bank or other nominee and present it to the judge of election with your ballot to be able to vote in person at the Lantheus Holdings special meeting. To request a legal proxy, please contact your broker, bank or other nominee.

Please carefully consider the information contained in this joint proxy statement/prospectus. Whether or not you plan to attend the Lantheus Holdings special meeting, Lantheus Holdings encourages you to vote via the Internet, by telephone or by mail so that your shares will be voted in accordance with your wishes even if you later decide not to attend the Lantheus Holdings special meeting.

In general, in accordance with applicable stock exchange rules, if your shares of Lantheus Holdings common stock are held in “street name” and you do not instruct your broker how to vote your shares, your brokerage firm, in its discretion, may either leave your shares unvoted or vote your shares on routine matters. However, a broker is precluded from exercising its voting discretion with respect to non-routine or “significant” matters, such as the approval of the stock issuance proposal and the approval of the Lantheus Holdings adjournment proposal. None of the proposals at the Lantheus Holdings special meeting are routine matters. As a result, if you hold your shares in “street name” through a brokerage account, your broker will not be able to exercise its discretion to vote uninstructed shares on any of the proposals presented at the special meeting.

If a beneficial owner of shares of Lantheus Holdings common stock held in “street name” does not give voting instructions to its broker, bank or other nominee, then those shares will not be present in person or represented by proxy at the Lantheus Holdings special meeting. A beneficial owner’s failure to instruct its broker, bank or other nominee how to vote shares of Lantheus Holdings common stock will have no effect on either of the proposals to be considered at the Lantheus Holdings special meeting as described in this joint proxy statement/prospectus, except to the extent it results in there being insufficient shares present at the Lantheus Holdings special meeting to establish a quorum.

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If you are a stockholder of record at the record date for the Lantheus Holdings special meeting (the close of business on [●]), you can revoke your proxy or change your vote by:

If you hold your shares in “street name” through a broker, bank or other nominee, you must contact your broker, bank or other nominee to change your vote or obtain a written legal proxy to vote your shares if you wish to cast your vote in person at the Lantheus Holdings special meeting.

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Innisfree M&A Incorporated

501 Madison Avenue, 20^th Floor

New York, New York 10022

Telephone (Toll-Free): (877) 750-9497

International Callers: (412) 232-3651

Banks and brokers may call collect: (212) 750-5833

For Progenics Stockholders

The adoption of the merger agreement by Progenics stockholders is a condition to the obligations of Progenics and Lantheus Holdings to complete the merger. Neither the approval of the Progenics adjournment proposal nor the approval of the Progenics compensation advisory proposal is a condition to the obligations of Progenics or Lantheus Holdings to complete the merger.

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If you hold shares of Progenics common stock directly in your name as a stockholder of record, you may vote via the Internet or by telephone by calling by following the directions on the enclosed proxy. In order

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to submit a proxy to vote via the Internet or by telephone, you will need the control number on your proxy card (which is unique to each Progenics stockholder to ensure all voting instructions are genuine and to prevent duplicate voting). Votes may be submitted via the Internet or by telephone 24 hours a day, seven days a week, and must be received by 11:59 p.m., Eastern Time, on the calendar day immediately preceding the Progenics special meeting. Please be aware that if you vote by telephone or over the Internet, you may incur costs such as telephone and Internet access charges for which you will be responsible.

If you hold shares of Progenics common stock in “street name,” meaning through a broker, bank or other nominee, you may vote via the Internet or by telephone only if Internet or telephone voting is made available by your broker, bank or other nominee. Please follow the voting instructions provided by your broker, bank or other nominee with these materials.

You may vote via the Internet or by telephone until 11:59 p.m., Eastern Time, on the calendar day immediately preceding the Progenics special meeting.

By Mail

If you hold shares of Progenics common stock directly in your name as a stockholder of record, in order to vote by mail, you may submit a proxy card. You will need to complete, sign and date your proxy card and return it using the postage-paid return envelope provided.

If you hold shares of Progenics common stock in “street name,” meaning through a broker, bank or other nominee, in order to provide voting instructions by mail you will need to complete, sign and date the voting instruction form provided by your broker, bank or other nominee with these materials and return it in the postage-paid return envelope provided. Your broker, bank or other nominee must receive your voting instruction form in sufficient time to vote your shares.

We recommend you mail your proxy timely to ensure receipt of your proxy before the date of the special meeting.

In Person

If you hold shares of Progenics common stock directly in your name as a stockholder of record, you may vote in person at the Progenics special meeting. Stockholders of record also may be represented by another person at the Progenics special meeting by executing a proper proxy designating that person and having that proper proxy be presented to the inspector of election with the applicable ballot at the Progenics special meeting.

If you hold shares of Progenics common stock in “street name,” meaning through a broker, bank or other nominee, you must obtain a written legal proxy from that broker, bank or other nominee and present it to the inspector of election with your ballot to be able to vote in person at the Progenics special meeting. To request a legal proxy, please contact your broker, bank or other nominee.

Please carefully consider the information contained in this joint proxy statement/prospectus. Whether or not you plan to attend the Progenics special meeting, Progenics encourages you to vote via the Internet, by telephone or by mail so that your shares will be voted in accordance with your wishes even if you later decide not to attend the Progenics special meeting.

In general, in accordance with applicable stock exchange rules, if your shares of Progenics common stock are held in “street name” and you do not instruct your broker how to vote your shares, your brokerage firm,

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in its discretion, may either leave your shares unvoted or vote your shares on routine matters. However, a broker is precluded from exercising its voting discretion with respect to non-routine or “significant” matters, such as the adoption of the merger agreement, the approval of the Progenics adjournment proposal and the approval of the Progenics compensatory advisory proposal. None of the proposals at the Progenics special meeting are routine matters. As a result, if you hold your shares in “street name” through a brokerage account, your broker will not be able to exercise its discretion to vote uninstructed shares on any of the proposals presented at the special meeting.

If a beneficial owner of shares of Progenics common stock held in “street name” does not give voting instructions to its broker, bank or other nominee, then those shares will not be present in person or represented by proxy at the Progenics special meeting. A beneficial owner’s failure to instruct its broker, bank or other nominee how to vote shares of Progenics common stock held in “street name” will have (1) the same effect as a vote “AGAINST” the merger agreement proposal; (2) no effect on the proposal to approve the Progenics adjournment proposal; and (3) no effect on the Progenics compensation advisory proposal, except to the extent it results in there being insufficient shares present at the Progenics special meeting to establish a quorum.

If you are a stockholder of record at the record date for the Progenics special meeting (the close of business on [●]), you can revoke your proxy or change your vote by:

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If you hold your shares in “street name” through a broker, bank or other nominee, you must contact your broker, bank or other nominee to change your vote or obtain a written legal proxy to vote your shares if you wish to cast your vote in person at the Progenics special meeting.

Progenics stockholders considering seeking appraisal should be aware that the “fair value” of their shares of Progenics common stock as determined by the Delaware Court of Chancery under Section 262 could be greater than, the same as or less than the merger consideration.

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If such Progenics stock option is an in-the-money option, it will be assumed by Lantheus Holdings and converted into an option, which is referred to in this joint proxy statement/prospectus as a Lantheus Holdings stock option, to purchase (a) that number of shares of Lantheus Holdings common stock (rounded down to the nearest whole share) equal to the product obtained by multiplying (i) the total number of shares of Progenics common stock subject to such Progenics stock option immediately prior to the effective time of the merger by (ii) the exchange ratio, (b) at a per-share exercise price (rounded up to the nearest whole cent) equal to the quotient obtained by dividing (i) the exercise price per share of Progenics common stock at which such Progenics stock option was exercisable immediately prior to the effective time of the merger by (ii) the exchange ratio. Each such Lantheus Holdings stock option is referred to in this joint proxy statement/prospectus as an in-the-money assumed option. Each in-the-money assumed option will continue to have the same terms and conditions (including the applicable time-vesting and/or performance-vesting conditions and any provisions for accelerated vesting) as applied to the corresponding Progenics in-the-money option immediately prior to the effective time of the merger.

In addition to an in-the-money assumed option, each holder of a Progenics in-the-money option will also receive either (a) with respect to any Progenics in-the-money option that is vested immediately prior to the effective time of the merger, which is referred to in this joint proxy statement/prospectus as a vested in-the-money option, one fully vested CVR for each share of Progenics common stock subject to such vested in-the-money option that will be payable under the terms of the CVR agreement, which is referred to in this joint proxy statement/prospectus as a vested CVR, or (b) with respect to any Progenics in-the-money option that is not vested immediately prior to the effective time of the merger, which is referred to in this joint proxy statement/prospectus as an unvested in-the-money option, one unvested CVR for each share of Progenics common stock subject to such unvested in-the-money option that will be subject to vesting upon the same terms and conditions (including the applicable time-vesting and/or performance-vesting conditions and any provisions for accelerated vesting) that applied to the corresponding Progenics in-the-money option and payable under the terms of the CVR agreement, which is referred to in this joint proxy statement/prospectus as an unvested CVR. However, if the holder of such unvested CVR is employed or in the service of Lantheus Holdings, the surviving corporation or one of their subsidiaries, on the date a payment is due under the CVR agreement, then such unvested CVR will be deemed vested on such date with respect to such payment. In the event that the employment or other service with Lantheus Holdings, the surviving corporation or one of their subsidiaries, of a holder of an unvested CVR is terminated for any reason prior to the vesting of the unvested CVR for any reason that would trigger the forfeiture of the corresponding unvested in-the-money option, such unvested CVR will be forfeited without payment.

If such Progenics stock option is an out-of-the-money option, it will be assumed by Lantheus Holdings and converted into an option to purchase (a) that number of shares of Lantheus Holdings common stock (rounded down to the nearest whole share) equal to the product obtained by multiplying (i) the total number

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of shares of Progenics common stock that were subject to such out-of-the-money option immediately prior to the effective time of the merger by (ii) the quotient, rounded to the nearest one hundredth, of (x) the average of the volume weighted average price paid per share of Progenics common stock on the date that the stockholder approvals required under the merger agreement are obtained and each of the complete trading days immediately following such date, ending with (and including) the last complete trading day prior to the closing date, divided by (y) the average of the volume weighted average price paid per share of Lantheus Holdings common stock on the date that the stockholder approvals required under the merger agreement are obtained and each of the complete trading days immediately following such date, ending with (and including) the last complete trading day prior to the closing date with such quotient referred to in this joint proxy statement/prospectus as the out-of-the-money option exchange ratio, (b) at a per-share exercise price (rounded up to the nearest whole cent) equal to the quotient obtained by dividing (i) the exercise price per share of Progenics common stock at which such Progenics stock option was exercisable immediately prior to the effective time of the merger by (ii) the out-of-the-money option exchange ratio. No CVRs will be issued in respect of out-of-the-money options. See “The Merger Agreement—Treatment of Progenics Stock Options” beginning on page 183 of this joint proxy statement/prospectus for further information.

Subject to the qualifications, exceptions, assumptions and limitations contained in “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Material U.S. Federal Income Tax Consequences” beginning on page 170 of this joint proxy statement/prospectus, if the merger does not qualify as a “reorganization” under Section 368(a) of the Code, then, for U.S. federal income tax purposes, a U.S. holder of Progenics common stock would recognize gain or loss in an amount equal to the difference, if any, between (i) the sum of the fair market values of the Lantheus Holdings common stock and the CVRs, as determined for U.S. federal income tax purposes, and any cash received in lieu of fractional shares and (ii) such holder’s adjusted tax basis in the Progenics common stock surrendered.

Each Progenics stockholder is urged to read the discussion in the section entitled “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Material U.S. Federal Income Tax Consequences” beginning on page 170 of this joint proxy statement/prospectus and to consult its tax advisor to determine the particular U.S. federal, state or local or non-U.S. income or other tax consequences to it of the merger.

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MacKenzie Partners, Inc.

1407 Broadway, 27^th Floor

New York, New York 10018

Toll-Free: (800) 322-2885

or

(212) 929-5500

Email: pgnx@mackenziepartners.com

For Both Lantheus Holdings Stockholders and Progenics Stockholders

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If you hold shares in “street name” through a broker, bank or other nominee, please instruct your broker, bank or other nominee to vote your shares by following the instructions that the broker, bank or other nominee provides to you with these materials.

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RISK FACTORS

In addition to the other information contained or incorporated by reference into this joint proxy statement/prospectus, including the matters addressed in “Cautionary Statement Regarding Forward-Looking Statements” beginning on page 74 of this joint proxy statement/prospectus, you should carefully consider the following risk factors in determining whether to vote for the merger agreement proposal or the stock issuance proposal, as applicable. You also should read and consider the risk factors associated with each of the businesses of Lantheus Holdings and Progenics because these risk factors may affect the operations and financial results of the combined company. These risks may be found under Part I, Item 1A, “Risk Factors” in each company’s Annual Report on Form 10-K for the year ended December 31, 2019 and future filings with the SEC, each of which is on file or will be filed with the SEC and all of which are incorporated by reference into this joint proxy statement/prospectus.

Risks Related to the Merger

Because the exchange ratio is fixed and will not be adjusted in the event of any changes in either Lantheus Holdings’ or Progenics’ stock price, and because of the uncertainty of the fair market value of, and the ultimate realization on, the CVRs, Progenics stockholders cannot be sure of the value of the merger consideration they will receive in the merger.

Upon completion of the merger, each share of Progenics common stock outstanding immediately prior to the completion of the merger (other than excluded shares and dissenting shares) will be converted into the right to receive 0.31 of a share of Lantheus Holdings common stock without interest and one CVR representing the right to receive, subject to the CVR cap, such stockholder’s pro rata share of aggregate cash payments equal to 40% of U.S. net sales generated by PyL in calendar years 2022 and 2023 in excess of $100 million and $150 million, respectively, as set forth in the CVR agreement. The exchange ratio is fixed and will not be adjusted for changes in the market price of either Lantheus Holdings common stock or Progenics common stock between the date the merger agreement was signed and completion of the merger. As a result, changes in the price of Lantheus Holdings common stock prior to the completion of the merger will affect the value of the Lantheus Holdings common stock that Progenics stockholders will receive upon completion of the merger.

The market price of shares of Lantheus Holdings common stock has fluctuated since the date of the announcement of the merger agreement and may continue to change through the date of each of the Lantheus Holdings and the Progenics special meetings and the date the merger is completed. For example, based on the range of closing prices of Lantheus Holdings common stock during the period from February 19, 2020, the last full trading day before the public announcement of the merger, through March 13, 2020, the latest practicable trading date before the date of this joint proxy statement/prospectus, the exchange ratio resulted in an implied value of the stock consideration ranging from a high of approximately $5.45 to a low of approximately $3.56 for each share of Progenics common stock. The actual market value of the Lantheus Holdings common stock received by holders of Progenics common stock may result in an implied value of the stock consideration outside this range. There is also uncertainty regarding the fair market value of the CVRs and whether any payment will ultimately be realized on the CVRs.

Stock price changes may result from a variety of factors, including, among others, general market and economic conditions, changes in Lantheus Holdings’ and Progenics’ respective businesses, operations and prospects, risks inherent in their respective businesses, changes in market assessments of the likelihood that the merger will be completed and/or the value that may be generated by the merger, and changes with respect to expectations regarding the timing of the merger and regulatory considerations. At the time of the Progenics special meeting, Progenics stockholders will not know with certainty the value of the shares of Lantheus Holdings common stock that they will receive upon completion of the merger.

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The merger is subject to the expiration or termination of applicable waiting periods and the receipt of approvals, consents or clearances from regulatory authorities that may impose conditions that could have an adverse effect on Lantheus Holdings, Progenics or the combined company or, if not obtained, could prevent completion of the merger.

Before the merger may be completed, any approvals, consents or clearances required in connection with the merger must have been obtained, in each case, under applicable law. Completion of the merger is conditioned upon, among other things, the expiration or termination of the waiting period (and any extension thereof) applicable to the merger under the HSR Act, which, as noted above, has been obtained by grant of early termination of the HSR Act waiting period on October 25, 2019. Notwithstanding the grant of early termination, at any time before or after the merger is completed, the Antitrust Division, the FTC, or U.S. state attorneys general could take action under the antitrust laws in opposition to the merger, including seeking to enjoin completion of the merger, condition completion of the merger upon the divestiture of assets, or impose restrictions on post-merger operations. Any such requirements or restrictions may prevent or delay completion of the merger or may reduce the anticipated benefits of the merger.

The merger is subject to conditions, some or all of which may not be satisfied, or completed on a timely basis, if at all. Failure to complete the merger could have material adverse effects on Lantheus Holdings’ and Progenics’ businesses.

The completion of the merger is subject to a number of conditions in addition to the termination or expiration of any applicable waiting period (and any extension thereof) under the HSR Act, including, among other conditions: (i) approval of the merger agreement proposal by Progenics stockholders at the Progenics special meeting; (ii) approval of the stock issuance proposal by Lantheus Holdings stockholders at the Lantheus Holdings special meeting; (iii) approval for the listing on the Nasdaq Global Market of the shares of Lantheus Holdings common stock to be issued in the merger and such other shares to be reserved for issuance in connection with the merger; (iv) the absence of any law enacted or order issued by a governmental authority of competent jurisdiction having the effect of making the merger illegal or otherwise prohibiting completion of the merger; (v) the accuracy of the representations and warranties made in the merger agreement by the other party, subject to the applicable materiality standards set forth in the merger agreement; (vi) the absence of any fact, circumstance, condition, development, change, event, occurrence or effect that has had or would reasonably be expected to have, individually or in the aggregate with all other facts, circumstances, conditions, developments, changes, events, occurrences or effects, a material adverse effect on Progenics since the date of the original merger agreement; (vii) performance or compliance in all material respects by the other party with all the agreements and covenants required to be performed by such party under the merger agreement on or prior to the closing date; and (viii) the effectiveness of the registration statement on Form S-4 relating to the merger and no stop order suspending the effectiveness of the registration statement and no proceedings for such purpose initiated or threatened by the SEC.

In addition, the merger agreement contains certain termination rights for both Lantheus Holdings and Progenics, including, among other things, (i) if the merger has not been completed by July 1, 2020, (ii) if the required approval of Lantheus Holdings stockholders or the Progenics stockholders is not obtained, (iii) if the other party willfully breaches its non-solicitation obligations in the merger agreement, (v) if the other party materially breaches its representations, warranties or covenants which breach or failure to perform would result in a failure to satisfy any condition to completion of the merger related to the accuracy of its representations and warranties or the performance of its covenants and agreements, and fails to cure such breach, (vi) if any law or order prohibiting the merger or the stock issuance has become final and nonappealable, or (vii) if the board of directors of the other party changes its recommendation in connection with the merger. If the merger is not completed, the ongoing business of Lantheus Holdings and Progenics may be materially adversely affected and, without realizing any of the benefits that they could have realized had the merger been completed, they will be subject to a number of risks, including the following:

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In addition, if the merger is not completed, Lantheus Holdings and Progenics could be subject to litigation related to any failure to complete the merger or related to any enforcement proceeding commenced against either Lantheus Holdings or Progenics to perform its obligations under the merger agreement. If any such risk materializes, it could adversely impact either Lantheus Holdings’ or Progenics’ ongoing business. Similarly, delays in the completion of the merger could, among other things, result in additional transaction costs, loss of revenue or other negative effects associated with uncertainty about completion of the merger and cause them not to realize some or all of the benefits that they expect to achieve if the merger is successfully completed within its expected timeframe. We cannot assure you that the conditions to the closing of the merger will be satisfied or waived or that the merger will be completed.

In addition, Progenics anticipates it being necessary to obtain additional financing in order to meet its cash requirements if the merger is not consummated. However, there can be no assurances that Progenics will be able to obtain additional capital on acceptable terms and in the amounts necessary to fully fund Progenics’ current operating expenses or reduced operating expenses reflecting delays or reductions in the scope of Progenics’ product development programs beyond 2020. These and other circumstances raise substantial doubt about Progenics’ ability to continue as a going concern if the merger is not consummated. Progenics’ independent registered public accounting firm has issued an opinion on Progenics’ financial statements as of and for the period ended December 31, 2019 included in Progenics’ Annual Report on Form 10-K, and incorporated by reference in this joint proxy statement/prospectus, that states that there is substantial doubt about Progenics’ ability to continue as a going concern and that the financial statements do not include any adjustments relating to the recoverability and classification of liabilities that might be necessary should Progenics be unable to continue as a going concern.

On March 15, 2020, Progenics, as borrower, and Lantheus Medical Imaging, as lender, entered into a bridge loan agreement, pursuant to which Lantheus Medical Imaging agreed to provide for a secured short-term loan to Progenics on or after May 1, 2020 in an aggregate principal amount of up to $10 million. The bridge loan matures on the earlier to occur of (a) September 30, 2020 and (b) the date on which Progenics enters into a debt financing or similar

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arrangements or any amendment to, or replacement of, its existing debt provided by one or more third parties following the termination date of the merger agreement, in either case, having aggregate net cash proceeds that exceed the amount then required to repay all obligations under the bridge loan agreement in full in cash. If such bridge loan is made by Lantheus Medical Imaging, there is no assurance that such borrowings will be repaid in accordance with the terms of the bridge loan agreement, or at all. See “Bridge Loan Agreement” beginning on page 210 of this joint proxy statement/prospectus for a more detailed description of the bridge loan agreement.

Uncertainties associated with the merger may cause a loss of management personnel and other key employees, and Lantheus Holdings and Progenics may have difficulty attracting and motivating management personnel and other key employees, which could adversely affect the future business and operations of the combined company.

Lantheus Holdings and Progenics are each dependent on the experience and industry knowledge of their respective management personnel and other key employees to execute their business plans. The combined company’s success after the completion of the merger will depend in part upon the ability of each of Lantheus Holdings and Progenics to attract, motivate and retain key management personnel and other key employees. Prior to completion of the merger, current and prospective employees of each of Lantheus Holdings and Progenics may experience uncertainty about their roles within the combined company following the completion of the merger, which may have an adverse effect on the ability of each of Lantheus Holdings and Progenics to attract, motivate or retain management personnel and other key employees. In addition, no assurance can be given that the combined company will be able to attract, motivate or retain management personnel and other key employees of each of Lantheus Holdings and Progenics to the same extent that Lantheus Holdings and Progenics have previously been able to attract or retain their own employees.

On February 28, 2020, Mr. Fabbio provided notice to the Progenics Board of his intention to resign as Progenics’ Chief Financial Officer, effective March 27, 2020. Mr. Fabbio has agreed to continue providing services to Progenics as a consultant following the effective date of his resignation until the earlier of the effective time of the merger and May 15, 2020 unless terminated by either party as set forth therein, as further described in the section entitled “Interests of Progenics’ Directors and Executive Officers in the Merger” beginning on page 211 of this joint proxy statement/prospectus.

Progenics’ executive officers and directors have interests in the merger that may be different from your interests as a stockholder of Progenics.

When considering the recommendation of the Progenics Board that Progenics stockholders vote in favor of the merger agreement proposal, the Progenics adjournment proposal and the compensation advisory proposal, Progenics stockholders should be aware that Progenics’ directors and executive officers have interests in the merger that may be different from, or in addition to, the interests of Progenics stockholders generally, including accelerated vesting of their Progenics stock options in connection with the merger (or, in the case of executive officers, a qualifying termination of employment on or within 12 months following the merger), certain retention payments that may be made to Progenics’ executive officers (other than Mr. Mims and Mr. Fabbio) in connection with the closing of the merger, and rights to ongoing indemnification and insurance coverage in accordance with the terms of certain indemnification agreements. In addition, pursuant to the merger agreement, at the effective time of the merger, the Lantheus Holdings Board will appoint Dr. Ber and Mr. Mäusli, who are currently members of the Progenics Board, to serve on the Lantheus Holdings Board. See “Interests of Progenics’ Directors and Executive Officers in the Merger” beginning on page 211 of this joint proxy statement/prospectus for a more detailed description of these interests. The Progenics Board and the Lantheus Holdings Board were aware of these interests and considered them, in addition to other matters, in evaluating, negotiating and approving the merger agreement and in recommending that Progenics stockholders adopt the merger agreement and that the Lantheus Holdings stockholders approve the stock issuance, respectively.

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The merger agreement limits the ability of both Lantheus Holdings and Progenics to pursue alternatives to the merger and may discourage other companies from trying to acquire either Lantheus Holdings or Progenics.

The merger agreement contains a no solicitation covenant that restricts both Lantheus Holdings’ and Progenics’ ability to (i) initiate or solicit or knowingly facilitate, knowingly induce or knowingly encourage any inquiry or the making of any proposal or offer that constitutes, or would reasonably be expected to lead to, a takeover proposal (as defined in “The Merger Agreement—No Solicitation,” beginning on page 193 of this joint proxy statement/prospectus), (ii) enter into, continue or otherwise participate in any discussions or negotiations regarding, furnish to any person any information or data with respect to, or cooperate in any way that would otherwise reasonably be expected to lead to, any proposal or offer that constitutes, or would reasonably be expected to lead to, any takeover proposal, (iii) submit to the stockholders of Progenics or Lantheus Holdings, as applicable, for their approval or adoption any takeover proposal, or (iv) agree or publicly announce an intention to take any of the foregoing actions. In the event either company receives a bona fide written takeover proposal, it must promptly communicate the receipt of such proposal and provide copies of all written materials provided, including the terms and conditions of such proposal, to the other party. If, in response to such proposals and subject to certain conditions, either company intends to effect a change in recommendation of its board of directors (as defined in “The Merger Agreement—No Solicitation,” beginning on page 193 of this joint proxy statement/prospectus), it must engage in good faith negotiations with the other party to amend the merger agreement in response to such competing takeover proposal before its board may make a change in recommendation. The merger agreement further provides that in the event of a termination of the merger agreement under certain specified circumstances, including a termination following a change in recommendation by the board of directors of either party or a willful breach of the no solicitation provision applicable to it, such party may be required to pay the other party a termination fee equal to $18,340,000 (see “The Merger Agreement—Termination Fees and Expenses” beginning on page 207 of this joint proxy statement/prospectus).

These provisions could discourage a potential third-party acquirer that might have an interest in acquiring all or a significant portion of Lantheus Holdings or Progenics from considering or proposing that acquisition, even if that party were prepared to pay consideration with a higher per-share value than the currently proposed merger consideration, in the case of Progenics, or that party were prepared to enter into an agreement that may be favorable to Lantheus Holdings or its stockholders, in the case of Lantheus Holdings. These provisions might also result in a potential third-party acquirer proposing to pay a lower price in a takeover proposal than it might otherwise have proposed to pay because of the added expense of the termination fee and other fees and expenses that may become payable in certain circumstances.

The shares of Lantheus Holdings common stock to be received by Progenics stockholders upon completion of the merger will have different rights from shares of Progenics common stock.

Upon completion of the merger, Progenics stockholders will no longer be stockholders of Progenics, but will instead become stockholders of Lantheus Holdings, and their rights as Lantheus Holdings stockholders will be governed by the terms of Lantheus Holdings’ amended and restated certificate of incorporation, as it may be amended from time to time, which is referred to in this joint proxy statement/prospectus as Lantheus Holdings’ certificate of incorporation, and Lantheus Holdings’ amended and restated by-laws, as they may be amended from time to time, which are referred to in this joint proxy statement/prospectus as Lantheus Holdings’ by-laws. The terms of Lantheus Holdings’ certificate of incorporation and Lantheus Holdings’ by-laws are in some respects materially different than the terms of Progenics’ amended and restated certificate of incorporation, as it may be amended from time to time, which is referred to in this joint proxy statement/prospectus as Progenics’ certificate of incorporation, and Progenics’ by-laws, as they may be amended from time to time, which are referred to in this joint proxy statement/prospectus as Progenics’ by-laws, which currently govern the rights of Progenics stockholders. See “Comparison of Stockholder Rights” beginning on page 235 of this joint proxy statement/prospectus for a discussion of the different rights associated with shares of Progenics common stock and shares of Lantheus Holdings common stock.

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Lantheus Holdings and Progenics may be targets of securities class action and derivative lawsuits that could result in substantial costs and may delay or prevent the merger from being completed.

Securities class action lawsuits and derivative lawsuits are often brought against public companies that have entered into merger agreements. As of March 13, 2020, six securities class action lawsuits were initially brought against Progenics and the Progenics Board alleging inadequate disclosure by Progenics in the registration statement filed on November 12, 2019 related to the merger. Three of such lawsuits were voluntarily dismissed without prejudice by plaintiffs, with no settlements from, or other agreed obligations by, the respective defendants thereunder. One of those lawsuits against Progenics that has not been dismissed also names Lantheus Holdings or one of its affiliates as defendants. In addition, by letter dated October 14, 2019, Progenics received the FRS demand under Section 220 of the DGCL to inspect its books and records concerning, among other things, the opposition to the consent solicitation commenced by Velan and the negotiation and execution of the original merger agreement, and asserting that the Progenics Board may have breached its fiduciary obligations. Lantheus Holdings and Progenics do not believe that these lawsuits have merit or will result in any material monetary damages payable by either Lantheus Holdings or Progenics. However, even if lawsuits are without merit, defending against any legal claims can result in substantial costs and divert management time and resources. An adverse judgment in a securities class action lawsuit or derivative lawsuit alleging significant monetary loss by the plaintiffs could result in monetary damages for Lantheus Holdings and Progenics, which could have a negative impact on Lantheus Holdings’ and Progenics’ respective liquidity and financial condition. Additionally, if a plaintiff is successful in obtaining an injunction prohibiting completion of the merger, then that injunction may delay or prevent the merger from being completed, or from being completed within the expected timeframe, which may adversely affect Lantheus Holdings’ and Progenics’ respective business, financial position and results of operation. See “—Background of the Merger and Certain Other Developments” beginning on page 91 of this joint proxy statement/prospectus.

Lantheus Holdings and Progenics are each subject to business uncertainties and contractual restrictions while the merger is pending, which could adversely affect the business and operations of Lantheus Holdings, Progenics or the combined company.

In connection with the pendency of the merger, it is possible that some customers, suppliers and other persons with whom Lantheus Holdings or Progenics has a business relationship may delay or defer certain business decisions or might decide to seek to terminate, change or renegotiate their relationships with Lantheus Holdings or Progenics, as the case may be, as a result of the merger, which could negatively affect Lantheus Holdings’ or Progenics’ current, or the combined company’s future, revenues, earnings and cash flows, as well as the market price of Lantheus Holdings or Progenics common stock, regardless of whether the merger is completed. Under the terms of the merger agreement, Lantheus Holdings and Progenics are each subject to certain restrictions on the conduct of its business prior to completing the merger, which could adversely affect each party’s ability to execute certain of its business strategies. Such limitations could adversely affect each party’s business and operations prior to the completion of the merger. Each of the risks described above may be exacerbated by delays or other adverse developments with respect to the completion of the merger.

The unaudited pro forma combined financial information and prospective financial information included in this joint proxy statement/prospectus are presented for illustrative purposes only and do not represent the actual financial position or results of operations of the combined company following completion of the merger.

The unaudited pro forma combined financial information and prospective financial information contained in this joint proxy statement/prospectus is presented for illustrative purposes only, contains a variety of adjustments, assumptions and preliminary estimates and does not represent the actual financial position or results of operations of Lantheus Holdings and Progenics prior to the merger or that of the combined company following the merger for several reasons. Among other things, the unaudited pro forma combined financial information does not reflect the projected realization of cost savings following completion of the merger. See the sections entitled “Certain Unaudited Pro Forma Condensed Combined Financial Statements,” “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Certain Unaudited Prospective Financial Information” and

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“Comparative Historical and Unaudited Pro Forma Combined Per Share Data” beginning on pages 59, 157 and 57, respectively, of this joint proxy statement/prospectus.

The actual financial positions and results of operations of Lantheus Holdings and Progenics prior to the merger and that of the combined company following the merger may not be consistent with, or evident from, and may differ materially and adversely from, the unaudited pro forma combined financial information or prospective financial information included in this joint proxy statement/prospectus. In addition, the assumptions used in preparing the unaudited pro forma combined financial information and/or the prospective financial information included in this joint proxy statement/prospectus may not be realized, may not prove to be accurate and may be affected by other factors, which could lead to material changes to the combined company’s business that are not reflected in the unaudited pro forma combined financial information.

The opinions of Progenics’ and Lantheus Holdings’ respective financial advisors do not reflect changes in circumstances that may have occurred or that may occur between the signing of the merger agreement and the completion of the merger.

Neither the Progenics Board nor the Lantheus Holdings Board has obtained updated opinions from their respective financial advisors as of the date of this joint proxy statement/prospectus, nor do either of them expect to receive updated, revised or reaffirmed opinions prior to the completion of the merger. Changes in the operations and prospects of Progenics or Lantheus Holdings, general market and economic conditions and other factors that may be beyond the control of Progenics or Lantheus Holdings, and on which Progenics’ and Lantheus Holdings’ financial advisors’ opinions were based, may significantly alter the value of Progenics or Lantheus Holdings or the share prices of Progenics common stock or Lantheus Holdings common stock by the time the merger is completed. The opinions do not speak as of the time the merger will be completed or as of any date other than the date of such opinions. Because Progenics’ and Lantheus Holdings’ financial advisors will not be updating their opinions, the opinions will not address the fairness of the merger consideration from a financial point of view at the time the merger is completed. The Lantheus Holdings Board’s recommendation that Lantheus Holdings stockholders approve the stock issuance proposal and the Progenics Board’s recommendation that Progenics stockholders approve the merger agreement proposal, however, are made as of the date of this joint proxy statement/prospectus. For a description of the opinions that the Progenics Board and the Lantheus Holdings Board received from their respective financial advisors, see “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Opinion of Lantheus Holdings’ Financial Advisor” and “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Opinion of Progenics’ Financial Advisor” beginning on pages 140 and 148, respectively, of this joint proxy statement/prospectus.

The merger may not occur, and if it does, it may not be accretive and may cause dilution to Lantheus Holdings earnings per share, which may negatively affect the market price of its common stock.

Although it is currently anticipated that the merger will occur and will be accretive to Lantheus Holdings’ adjusted earnings per share by 2022 and GAAP-reported earnings per share by 2023, these expectations are based on assumptions about Lantheus Holdings’ and Progenics’ business and preliminary estimates, which may change materially. Certain other expenses to be paid in connection with the merger may cause dilution to Lantheus Holdings’ earnings per share or decrease or delay the expected accretive effect of the merger and could cause a decrease in the market price of the Lantheus Holdings common stock. In addition, the merger may not occur or Lantheus Holdings could encounter additional transaction-related costs or other factors such as the failure to realize all of the benefits anticipated in the merger, including synergies, cost savings, innovation and operational efficiencies and revenue growth from the combination. All of these factors could cause dilution to Lantheus Holdings’ earnings per share or decrease or delay the expected accretive effect of the merger and cause a decrease in the market price of Lantheus Holdings common stock.

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Progenics stockholders have appraisal rights under Delaware law.

Under Delaware law, Progenics stockholders who do not vote in favor of adoption of the merger agreement and who otherwise properly perfect their rights will be entitled to “appraisal rights” in connection with the proposed merger, which generally entitle Progenics stockholders to receive, in lieu of the merger consideration, a cash payment of an amount determined by the Delaware Court of Chancery to be equal to the fair value of their Progenics common stock as of the effective time of the merger. The appraised value would be determined by the Court of Chancery and could be less than, the same as, or more than the merger consideration. Under Delaware law, stockholders are generally entitled to statutory interest on an appraisal award at a rate equal to 5% above the Federal Reserve discount rate compounded quarterly from the closing date of the merger until the award is actually paid. Progenics stockholders who have properly demanded appraisal rights must file a petition for appraisal with the Court of Chancery within 120 days after the effective date of the merger. Should a material number of Progenics stockholders exercise appraisal rights and should the Court determine that the fair value of such shares of Progenics common stock is materially greater than the merger consideration, Lantheus Holdings will be required to pay significantly more than anticipated in connection with the proposed merger, which could adversely affect the liquidity and financial condition of the combined company. For a more detailed description of the appraisal rights available to Progenics stockholders, see the section entitled “Appraisal or Dissenters’ Rights for Progenics Stockholders” beginning on page 166 of this joint proxy statement/prospectus and the full text of Section 262, attached as Annex E to this joint proxy statement/prospectus.

There can be no assurances that Progenics stockholders will not be required to recognize gain for U.S. federal income tax purposes upon the exchange of Progenics common stock for the merger consideration.

The merger is intended to qualify as a tax-deferred “reorganization” within the meaning of Section 368(a) of the Code, which is referred to in this joint proxy statement/prospectus as the intended tax treatment, and Lantheus Holdings and Progenics have agreed not to report or take any position for U.S. federal, state or local income tax purposes that is inconsistent with the intended tax treatment (except to the extent required by a “determination” as defined in Section 1313(a) of the Code). There can be no assurance, however, that the merger will so qualify. The closing of the merger is not conditioned on the merger qualifying for the intended tax treatment, and it is not contemplated that a tax opinion will be required or delivered as a condition to the closing of the merger. Neither Lantheus Holdings nor Progenics has requested a ruling from the IRS regarding any of the U.S. federal income tax consequences of the merger. Accordingly, there can be no assurance that the IRS will not assert, or that a court would not sustain, a position contrary to the intended tax treatment or any of the conclusions set forth herein. Progenics stockholders should therefore consult their own tax advisors to determine the U.S. federal income tax consequences of the merger to them.

If the IRS or a court determines that the merger does not qualify as a “reorganization” within the meaning of Section 368(a) of the Code, a U.S. holder of Progenics common stock generally would recognize gain or loss upon the exchange of Progenics common stock for the merger consideration pursuant to the merger in an amount equal to the difference, if any, between (i) the sum of the fair market values of the Lantheus Holdings common stock and the CVRs, as determined for U.S. federal income tax purposes, and any cash received in lieu of fractional shares and (ii) such holder’s adjusted tax basis in the Progenics common stock surrendered. You should read the section “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Material U.S. Federal Income Tax Consequences” beginning on page 170 of this joint proxy statement/prospectus and consult your own tax advisors regarding the U.S. federal income tax consequences of the transaction to you in your particular circumstances.

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Risks Related to the CVRs

Progenics stockholders may not receive any payments under the CVRs, which makes it difficult to value the CVRs, and payments under the CVRs are subject to an aggregate payment cap.

Under the merger agreement, in addition to the stock consideration, holders of shares of Progenics common stock have the right to receive one CVR for each share of Progenics common stock held by such person. Each CVR will entitle its holder to receive, subject to the CVR cap, his, her or its pro rata share of aggregate cash payments equal to 40% of U.S. net sales generated by PyL in calendar years 2022 and 2023 in excess of $100 million and $150 million, respectively. The CVRs will not have any voting or dividend rights and will not represent any equity or ownership interest in Lantheus Holdings, Merger Sub, Progenics or any of their respective affiliates. Therefore, Progenics stockholders’ right to receive any future payment with respect to the CVRs will be contingent solely upon the achievement of the foregoing milestones within the specified time periods and other terms and conditions of the CVR agreement, which may or may not occur and may be outside the control of Lantheus Holdings and Progenics. If the milestones are not achieved, no payment will be made under the CVRs and the CVRs will expire valueless. Accordingly, the value, if any, of the CVRs is speculative, and the CVRs may ultimately have no value at all.

In addition, payments under the CVRs are subject to an aggregate payment cap. The sum of (i) the aggregate amount of payments paid or payable pursuant to the CVR agreement (including any interest on such amounts paid or payable to the rights agent or any CVR holder) and (ii) the amount of any other cash or the fair market value of any property (other than Lantheus Holdings common stock or the CVRs) paid or payable to Progenics stockholders as consideration pursuant to the merger agreement will not (A) exceed 19.9% of the aggregate amount of consideration paid or payable to Progenics stockholders in the merger or (B) constitute an amount the payment of which, in the opinion of nationally recognized tax counsel, would more likely than not prevent the merger from satisfying the requirement of Section 368(a)(2)(E)(ii) of the Code. For a more detailed description of the CVRs, see the section entitled “Description of the CVRs” beginning on page 225 of this joint proxy statement/prospectus.

The CVRs are nontransferable.

The CVRs are nontransferable, meaning that they may not be sold, assigned, transferred, pledged, encumbered or in any other manner transferred or disposed of either in whole or in part, other than in certain limited circumstances. The CVRs will not be registered as securities and they will not be listed or traded on any stock exchange in the United States or elsewhere. Therefore, the CVRs are not liquid and Progenics stockholders will not be permitted to sell or transfer them, except in certain limited circumstances. This means that a holder of CVRs may not have any ability to recognize the value of any payment to be made in accordance with the CVR agreement prior to the receipt of such a payment, if any.

Lantheus Holdings’ obligation to obtain FDA approval for PyL and commercialize it in a manner that maximizes net sales is based on “diligent efforts,” which allows for consideration of a variety of factors to determine the efforts Lantheus Holdings is required to take; accordingly, under certain circumstances, Lantheus Holdings may not be required to take certain actions to achieve these goals, which would have an adverse effect on the value, if any, of the CVRs.

From and after the effective time of the merger, Lantheus Holdings has agreed to use “diligent efforts” to obtain FDA Approval for and commercially launch PyL as soon as practicable and thereafter commercialize PyL in a manner that maximizes net sales. However, the CVR agreement definition of “diligent efforts” allows for the consideration of a variety of factors in determining the efforts Lantheus Holdings is required to use to achieve these goals, and it does not require Lantheus Holdings to take all possible actions to achieve them. Under the CVR agreement, the definition of “diligent efforts” requires Lantheus Holdings to use a level of effort, expertise and resources consistent with those efforts, expertise and resources normally used by persons in the medical diagnostics business similar in size and resources to Lantheus Holdings and its affiliates with respect to

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developing, seeking regulatory approval for and commercializing a product or product candidate that is of similar market potential at a similar stage in its development or product life to PyL.

The U.S. federal income tax treatment of the CVRs is uncertain.

There is no legal authority directly addressing the U.S. federal income tax treatment of the CVRs or the treatment of payments that may be received pursuant to the CVRs. Accordingly, the amount, timing and character of any gain, income or loss with respect to the CVRs are uncertain. Due to the legal and factual uncertainties regarding the tax treatment of the CVRs, U.S. holders are urged to consult their own tax advisors to determine the timing and characterization of income, gain or loss resulting from the receipt of the CVRs and payments pursuant to, sale or other disposition (in certain limited circumstances) of, and the expiration of, the CVRs. For a more detailed summary of the material U.S. federal income tax treatment of the CVRs, see “Lantheus Holdings Proposal I: Approval of the Stock Issuance and Progenics Proposal I: Adoption of the Merger Agreement—Material U.S. Federal Income Tax Consequences” beginning on page 170.

Risks Related to the Combined Company After Completion of the Merger

The combined company may be unable to successfully integrate the Progenics business into the Lantheus Holdings business and realize the anticipated benefits of the merger.

The success of the merger will depend, in part, on the combined company’s ability to successfully combine the business of Progenics with the business of Lantheus Holdings, which currently operate as independent public companies, and realize the anticipated benefits, including synergies, cost savings, innovation and operational efficiencies and revenue growth from the combination. If the combined company is unable to achieve these objectives within the anticipated time frame, or at all, the anticipated benefits may not be realized fully or at all, or may take longer to realize than expected and the value of the combined company’s common stock may be harmed. The merger involves the integration of Progenics’ business into Lantheus Holdings’ existing business, which is expected to be a complex, costly and time-consuming process. Lantheus Holdings and Progenics have not previously completed a transaction comparable in size or scope to the merger. The integration may result in material challenges, including, without limitation:

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Many of these factors will be outside of the combined company’s control and any one of them could result in delays, increased costs, decreases in the amount of expected revenues and diversion of management’s time and energy, which could materially affect the combined company’s financial position, results of operations and cash flows. Lantheus Holdings will also be responsible for the implementation of the CVRs, and will incur costs in connection therewith, including costs of maintaining a rights agent and the preparation of any applicable net sales statements, among other costs. Lantheus Holdings and Progenics have operated, and until completion of the merger will continue to operate, independently. Lantheus Holdings and Progenics are currently permitted to conduct only limited planning for the integration of the two companies following the merger and have not yet determined the exact nature of how the businesses and operations of the two companies will be combined after the combination. The actual integration of Progenics with Lantheus Holdings’ business may result in additional or unforeseen expenses, and the anticipated benefits of the integration plan may not be realized. These integration matters could have an adverse effect on (i) each of Lantheus Holdings and Progenics during this transition period and (ii) the combined company for an undetermined period after completion of the merger. In addition, any actual cost savings of the merger could be less than anticipated.

Completion of the merger may trigger change in control or other provisions in certain agreements to which Progenics or its subsidiaries are a party, which may have an adverse impact on the combined company’s business and results of operations.

The completion of the merger may trigger change in control and other provisions in certain agreements to which Progenics or its subsidiaries are a party. If Lantheus Holdings and Progenics are unable to negotiate waivers of those provisions, the counterparties may exercise their rights and remedies under the agreements, potentially terminating the agreements or seeking monetary damages. Even if Lantheus Holdings and Progenics are able to negotiate waivers, the counterparties may require a fee for such waivers or seek to renegotiate the agreements on terms less favorable to Progenics or the combined company. Any of the foregoing or similar developments may have an adverse impact on the combined company’s business and results of operations.

The financial analyses and forecasts considered by Lantheus Holdings and Progenics and their respective financial advisors may not be realized, which may adversely affect the market price of Lantheus Holdings common stock following the completion of the merger.

In performing their financial analyses and rendering their opinions related to the merger, each of the respective financial advisors to Lantheus Holdings and Progenics relied on, among other things, internal stand-alone financial analyses and forecasts as separately provided by Lantheus Holdings and Progenics, respectively. See “Opinion of Lantheus Holdings’ Financial Advisor” and “Opinion of Progenics’ Financial Advisor” beginning on pages 140 and 148, respectively. These analyses and forecasts were prepared by, or as directed by, the management of Lantheus Holdings or the management of Progenics, as applicable. None of these analyses or forecasts were prepared with a view towards public disclosure or compliance with the published guidelines of the SEC, the U.S. Generally Accepted Accounting Principles, which is referred to in this joint proxy statement/prospectus as GAAP, or the guidelines established by the American Institute of Certified Public Accountants for preparation and presentation of financial forecasts. These projections are inherently based on various estimates and assumptions that are subject to the judgment of those preparing them. These projections are also subject to significant economic, competitive, industry and other uncertainties and contingencies, all of which are difficult or impossible to predict and many of which are beyond the control of Lantheus Holdings and Progenics. There can be no assurance that Lantheus Holdings’ or Progenics’ financial condition or results of operations will be consistent with those set forth in such analyses and forecasts, which could have an adverse impact on the market price of Lantheus Holdings common stock or the financial position of the combined company following the merger.

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The combined company is expected to incur substantial expenses related to the completion of the merger and the integration of the Progenics business with Lantheus Holdings’ business.

The combined company is expected to incur substantial expenses in connection with the completion of the merger and the integration of the Progenics business with Lantheus Holdings’ business. There are a large number of processes, policies, procedures, operations, technologies and systems that must be integrated, including purchasing, accounting and finance, sales, payroll, pricing, revenue management, marketing and benefits. The substantial majority of these costs will be non-recurring expenses related to the merger, facilities and systems consolidation costs. The combined company may incur additional costs to maintain employee morale and to attract, motivate or retain management personnel or key employees. The combined company will also incur transaction fees and costs related to formulating integration plans for the combined business, and the execution of these plans may lead to additional unanticipated costs. These incremental transaction and acquisition-related costs may exceed the savings the combined company expects to achieve from the elimination of duplicative costs and the realization of other efficiencies related to the integration of the businesses, particularly in the near term and in the event there are material unanticipated costs.

Current Lantheus Holdings stockholders and Progenics stockholders will have a reduced ownership and voting interest after the merger and will exercise less voting power and less influence over the management of the combined company.

Upon completion of the merger, Lantheus Holdings expects to issue approximately 26,844,956 shares of Lantheus Holdings common stock to Progenics stockholders in connection with the transactions contemplated by the merger agreement. As a result, Lantheus Holdings and Progenics estimate that, immediately after the completion of the merger, Lantheus Holdings stockholders will own approximately 60% of the outstanding shares of common stock of the combined company (based on fully diluted shares outstanding) and former Progenics stockholders will own approximately 40% of the outstanding shares of common stock of the combined company (based on fully diluted shares outstanding). In addition, shares of Lantheus Holdings common stock may be issued from time to time following the effective time of the merger to holders of Progenics stock options on the terms set forth in the merger agreement. See “The Merger Agreement—Treatment of Progenics Stock Options” beginning on page 183 of this joint proxy statement/prospectus for a more detailed explanation.

Consequently, current Lantheus Holdings stockholders in the aggregate will have less voting power and less influence over the management and policies of Lantheus Holdings than they currently have over the management and policies of Lantheus Holdings, and current Progenics stockholders in the aggregate will have significantly less voting power and less influence over the management and policies of Lantheus Holdings than they currently have over the management and policies of Progenics.

Risks Related to Lantheus Holdings and Progenics

A pandemic, epidemic or outbreak of an infectious disease, such as COVID-19, or coronavirus, may materially and adversely affect Lantheus Holdings or Progenics and their respective financial results.

The recent outbreak of COVID-19 originated in Wuhan, China, in December 2019 and has since spread throughout the world including the United States and Europe. The spread of COVID-19 has already affected the global economy and may adversely affect Lantheus Holdings’ or Progenics’ operations and businesses by causing a period of business disruption, including the potential interruption of global supply chains, manufacturing activities, logistics, radiopharmacies and other distribution channels as well as commercial and clinical development activities. Also, this outbreak may impact the operations of hospitals and clinics at which Lantheus Holdings’ or Progenics’ commercial products are used or product candidates are tested, and it may affect the number of medical procedures in which those products are used or product candidates are tested, thereby potentially reducing demand for commercial products and delaying clinical development of product candidates. In addition, there could be a potential effect of COVID-19 on FDA or other health or regulatory

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authorities, which could result in delays of reviews and approvals, including with respect to Lantheus Holdings’ or Progenics’ product candidates.

Neither Lantheus Holdings nor Progenics can presently predict the scope and severity of any potential business shutdowns or disruptions, but if Lantheus Holdings or Progenics or any of the third parties with whom Lantheus Holdings or Progenics engages were to experience shutdowns or other business disruptions, Lantheus Holdings’ or Progenics’ ability to conduct business in the manner and on the timelines presently planned could be materially and negatively impacted, which could have a material adverse effect on Lantheus Holdings’ or Progenics’ business and their results of operation and financial condition.

Additional Risks Related to Lantheus Holdings and Progenics

Lantheus Holdings and Progenics are, and following completion of the merger Lantheus Holdings will continue to be, subject to the risks described in Part I, Item 1A in Lantheus Holdings’ Annual Report on Form 10-K for the year ended December 31, 2019, filed with the SEC on February 25, 2020, and Part I, Item 1A in Progenics’ Annual Report on Form 10-K for the year ended December 31, 2019, filed with the SEC on March 13, 2020, and as updated by their future filings with the SEC, in each case, incorporated by reference into this joint proxy statement/prospectus. See “Where You Can Find More Information” beginning on page 260 of this joint proxy statement/prospectus.

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SELECTED HISTORICAL CONSOLIDATED FINANCIAL DATA OF LANTHEUS HOLDINGS

The following tables present selected historical consolidated financial data of Lantheus Holdings. The selected historical consolidated financial data of Lantheus Holdings for the fiscal years ended December 31, 2019, 2018 and 2017 and as of December 31, 2019 and 2018 are derived from Lantheus Holdings’ audited consolidated financial statements and related notes contained in its Annual Report on Form 10-K for the fiscal year ended December 31, 2019, which is incorporated by reference into this joint proxy statement/prospectus. The selected historical consolidated financial data of Lantheus Holdings for the fiscal years ended December 31, 2016 and 2015, and as of December 31, 2017, 2016 and 2015, have been derived from Lantheus Holdings’ audited consolidated financial statements for such years, which have not been incorporated by reference into this joint proxy statement/prospectus.

The following selected historical consolidated financial data of Lantheus Holdings set forth below is only a summary and is not necessarily indicative of future results. You should read the following information in conjunction with Lantheus Holdings’ audited consolidated financial statements contained in its Annual Report on Form 10-K for the year ended December 31, 2019, including “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and the notes to Lantheus Holdings’ consolidated financial statements for significant events affecting the comparability of results as well as material uncertainties regarding Lantheus Holdings’ future financial condition and results of operations in its entirety. See the section entitled “Where You Can Find More Information” beginning on page 260 of this joint proxy statement/prospectus.

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SELECTED HISTORICAL CONSOLIDATED FINANCIAL DATA OF PROGENICS

The following tables present selected historical consolidated financial data of Progenics. The selected historical consolidated financial data of Progenics for the fiscal years ended December 31, 2019, 2018 and 2017 and as of December 31, 2019 and 2018 are derived from Progenics’ audited consolidated financial statements and related notes contained in its Annual Report on Form 10-K for the year ended December 31, 2019, which is incorporated by reference into this joint proxy statement/prospectus. The selected historical consolidated financial data of Progenics for the fiscal years ended December 31, 2016 and 2015 and as of December 31, 2017, 2016 and 2015 are derived from Progenics’ audited consolidated financial statements for such years, which have not been incorporated by reference into this joint proxy statement/prospectus.

The following selected historical consolidated financial data of Progenics set forth below is only a summary and is not necessarily indicative of future results. You should read the following information in conjunction with Progenics’ audited consolidated financial statements contained in its Annual Report on Form 10-K for the year ended December 31, 2019, including “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and the notes to Progenics’ consolidated financial statements for significant events affecting the comparability of results as well as material uncertainties regarding Progenics’ future financial condition and results of operations. See the section entitled “Where You Can Find More Information” beginning on page 260 of this joint proxy statement/prospectus.

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COMPARATIVE HISTORICAL AND UNAUDITED

PRO FORMA COMBINED PER SHARE DATA

The following table sets forth selected historical and unaudited pro forma combined per share information for Lantheus Holdings and Progenics.

Historical Per Share of Common Stock Information of Lantheus Holdings and Progenics. The historical per share of common stock information of each of Lantheus Holdings and Progenics below is derived from the audited consolidated financial statements of each of Lantheus Holdings and Progenics as of and for the year ended December 31, 2019.

Unaudited Pro Forma Combined Per Lantheus Holdings Share of Common Stock Data. The Lantheus Holdings unaudited pro forma combined per share of common stock data set forth below gives effect to the merger under the acquisition method of accounting as if the merger had been effective on January 1, 2019, the first day of Lantheus Holdings’ fiscal year ended December 31, 2019. The unaudited pro forma combined book value per share of Lantheus Holdings common stock data set forth below gives effect to the merger under the acquisition method of accounting as if the merger had been effective December 31, 2019, assuming that each outstanding share of Progenics common stock had been converted into shares of Lantheus Holdings common stock based on the exchange ratio of 0.31.

The acquisition method of accounting is based on ASC 805, and uses the fair value concepts defined in Accounting Standards Codification 820, Fair Value Measurements (“ASC 820”). Acquisition accounting requires, among other things, that certain assets acquired and liabilities assumed be recognized at their fair values as of the acquisition date. The pro forma adjustments reflect Lantheus Holdings’ provisional estimates of fair value for certain assets and liabilities of Progenics. Differences between these preliminary estimates and the final fair values determined as part of acquisition accounting upon closing of the transaction will occur, and these differences could have a material impact on the unaudited pro forma combined per share information set forth in the following table.

The unaudited pro forma combined per share of Lantheus Holdings common stock data is presented for illustrative purposes only and does not purport to represent the actual financial position or results of operations that Lantheus Holdings would have achieved had the companies been combined during these periods or to project the future financial position or results of operations that Lantheus Holdings may achieve after completion of the merger.

Unaudited Pro Forma Combined Per Progenics Equivalent Share Data. The Progenics unaudited pro forma combined per Progenics equivalent share data set forth below shows the effect of the merger from the perspective of an owner of shares of Progenics common stock. The information was calculated by multiplying the unaudited pro forma combined per share of Lantheus Holdings common stock amounts by the exchange ratio of 0.31.

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General Information. You should read the below information in conjunction with the selected historical consolidated financial data included elsewhere in this joint proxy statement/prospectus and the historical consolidated financial statements of Lantheus Holdings and Progenics and related notes that have been filed with the SEC, certain of which are incorporated by reference into this joint proxy statement/prospectus. See “Selected Historical Consolidated Financial Data of Lantheus Holdings,” “Selected Historical Consolidated Financial Data of Progenics” and “Where You Can Find More Information” beginning on pages 54, 55 and 260, respectively, of this joint proxy statement/prospectus. The unaudited pro forma combined per share of Lantheus Holdings common stock data and the unaudited pro forma combined per Progenics equivalent share data is derived from, and should be read in conjunction with, the Lantheus Holdings and Progenics unaudited pro forma condensed combined financial statements and related notes included in this joint proxy statement/prospectus. See “Certain

Unaudited Pro Forma Condensed Combined Financial Statements” beginning on page 59 of this joint proxy statement/prospectus.

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