SECURITIES AND EXCHANGE COMMISSION
                             Washington, D.C. 20549

                                  SCHEDULE 13D

                   Under the Securities Exchange Act of 1934*

                       Ligand Pharmaceuticals Incorporated
                       -----------------------------------
                                (Name of Issuer)

                    Common Stock, par value $0.001 per share
                    ----------------------------------------
                         (Title of Class of Securities)

                                    53220K207
                                    ---------
                      (CUSIP Number of Class of Securities)

                                 Daniel S. Loeb
                                 Third Point LLC
                                 390 Park Avenue
                               New York, NY 10022
                                 (212) 224-7400
                                 --------------
                  (Name, Address and Telephone Number of Person
                Authorized to Receive Notices and Communications)

                                   Copies to:
                              Jack H. Nusbaum, Esq.
                          Willkie Farr & Gallagher LLP
                               787 Seventh Avenue
                             New York, NY 10019-6099
                                 (212) 728-8000

                               September 13, 2005
                               ------------------
                          (Date of Event which Requires
                            Filing of this Schedule)

If the filing person has previously filed a statement on Schedule 13G to report
the acquisition which is the subject of this Schedule 13D, and is filing this
schedule because of ss.ss. 240.13d-1(e), 240.13d-1(f) or 240.13d-1(g), check the
following box: [ ]

NOTE: Schedules filed in paper format shall include a signed original and five
copies of the schedule, including all exhibits. See Rule 240.13d-7 for other
parties to whom copies are to be sent.

* The remainder of this cover page shall be filled out for a reporting person's
initial filing on this form with respect to the subject class of securities, and
for any subsequent amendment containing information which would alter
disclosures provided in a prior cover page.

The information required on the remainder of this cover page shall not be deemed
to be "filed" for the purpose of Section 18 of the Securities Exchange Act of
1934 ("Act") or otherwise subject to the liabilities of that section of the Act
but shall be subject to all other provisions of the Act (however, see the
Notes).



                                  SCHEDULE 13D


-------------------                                           ------------------
CUSIP No. 53220K207                                           Page 2 of 10 Pages
-------------------                                           ------------------
----------- --------------------------------------------------------------------
    1       NAME OF REPORTING PERSON
            I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)

            Daniel S. Loeb
----------- --------------------------------------------------------------------
    2       CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP             (a) [ ]
                                                                         (b) [X]
--------------------------------------------------------------------------------
    3       SEC USE ONLY
--------------------------------------------------------------------------------
    4       SOURCE OF FUNDS*

            AF
----------- --------------------------------------------------------------------
    5       CHECK BOX IF DISCLOSURE OF LEGAL PROCEEDING IS REQUIRED PURSUANT TO
            ITEMS 2(d) or 2(e) [ ]
----------- --------------------------------------------------------------------
    6       CITIZENSHIP OR PLACE OF ORGANIZATION

            United States
--------------------- --------- ------------------------------------------------
                         7      SOLE VOTING POWER

                                0
    NUMBER OF         --------- ------------------------------------------------
     SHARES              8      SHARED VOTING POWER
  BENEFICIALLY
    OWNED BY                    7,000,000
      EACH            --------- ------------------------------------------------
    REPORTING            9      SOLE DISPOSITIVE POWER
   PERSON WITH
                                0
                      --------- ------------------------------------------------
                         10     SHARED DISPOSITIVE POWER

                                7,000,000
----------- --------------------------------------------------------------------
    11      AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH PERSON

            7,000,000
----------- --------------------------------------------------------------------
    12      CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (11) EXCLUDES CERTAIN
            SHARES* [ ]
----------- --------------------------------------------------------------------
    13      PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (11)

            9.47%
----------- --------------------------------------------------------------------
    14      TYPE OF REPORTING PERSON*

            IN
----------- --------------------------------------------------------------------



                                  SCHEDULE 13D


-------------------                                           ------------------
CUSIP No. 53220K207                                           Page 3 of 10 Pages
-------------------                                           ------------------
----------- --------------------------------------------------------------------
    1       NAME OF REPORTING PERSON
            I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)

            Third Point LLC             I.D. #13-3922602
----------- --------------------------------------------------------------------
    2       CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP             (a) [ ]
                                                                         (b) [X]
--------------------------------------------------------------------------------
    3       SEC USE ONLY
--------------------------------------------------------------------------------
    4       SOURCE OF FUNDS*

            AF
----------- --------------------------------------------------------------------
    5       CHECK BOX IF DISCLOSURE OF LEGAL PROCEEDING IS REQUIRED PURSUANT TO
            ITEMS 2(d) or 2(e) [ ]
----------- --------------------------------------------------------------------
    6       CITIZENSHIP OR PLACE OF ORGANIZATION

            Delaware
--------------------- --------- ------------------------------------------------
                         7      SOLE VOTING POWER

                                0
    NUMBER OF         --------- ------------------------------------------------
     SHARES              8      SHARED VOTING POWER
  BENEFICIALLY
    OWNED BY                    7,000,000
      EACH            --------- ------------------------------------------------
    REPORTING            9      SOLE DISPOSITIVE POWER
   PERSON WITH
                                0
                      --------- ------------------------------------------------
                         10     SHARED DISPOSITIVE POWER

                                7,000,000
----------- --------------------------------------------------------------------
    11      AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH PERSON

            7,000,000
----------- --------------------------------------------------------------------
    12      CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (11) EXCLUDES CERTAIN
            SHARES* [ ]
----------- --------------------------------------------------------------------
    13      PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (11)

            9.47%
----------- --------------------------------------------------------------------
    14      TYPE OF REPORTING PERSON*

            OO
----------- --------------------------------------------------------------------



                                  SCHEDULE 13D


-------------------                                           ------------------
CUSIP No. 53220K207                                           Page 4 of 10 Pages
-------------------                                           ------------------
----------- --------------------------------------------------------------------
    1       NAME OF REPORTING PERSON
            I.R.S. IDENTIFICATION NOS. OF ABOVE PERSONS (ENTITIES ONLY)

            Third Point Offshore Fund, Ltd.
----------- --------------------------------------------------------------------
    2       CHECK THE APPROPRIATE BOX IF A MEMBER OF A GROUP             (a) [ ]
                                                                         (b) [X]
--------------------------------------------------------------------------------
    3       SEC USE ONLY
--------------------------------------------------------------------------------
    4       SOURCE OF FUNDS*

            AF
----------- --------------------------------------------------------------------
    5       CHECK BOX IF DISCLOSURE OF LEGAL PROCEEDING IS REQUIRED PURSUANT TO
            ITEMS 2(d) or 2(e) [ ]
----------- --------------------------------------------------------------------
    6       CITIZENSHIP OR PLACE OF ORGANIZATION

            Cayman Islands
--------------------- --------- ------------------------------------------------
                         7      SOLE VOTING POWER

                                0
    NUMBER OF         --------- ------------------------------------------------
     SHARES              8      SHARED VOTING POWER
  BENEFICIALLY
    OWNED BY                    4,552,600
      EACH            --------- ------------------------------------------------
    REPORTING            9      SOLE DISPOSITIVE POWER
   PERSON WITH
                                0
                      --------- ------------------------------------------------
                         10     SHARED DISPOSITIVE POWER

                                4,552,600
----------- --------------------------------------------------------------------
    11      AGGREGATE AMOUNT BENEFICIALLY OWNED BY EACH PERSON

            4,552,600
----------- --------------------------------------------------------------------
    12      CHECK BOX IF THE AGGREGATE AMOUNT IN ROW (11) EXCLUDES CERTAIN
            SHARES* [ ]
----------- --------------------------------------------------------------------
    13      PERCENT OF CLASS REPRESENTED BY AMOUNT IN ROW (11)

            6.16%
----------- --------------------------------------------------------------------
    14      TYPE OF REPORTING PERSON*

            OO
----------- --------------------------------------------------------------------



     This Schedule 13D is being filed on behalf of Third Point LLC, a Delaware
limited liability company (the "Management Company"), Third Point Offshore Fund,
Ltd., a Cayman Island limited liability exempted company (the "Offshore Fund"),
and Daniel S. Loeb, an individual ("Mr. Loeb" and, together with the Management
Company and the Offshore Fund, the "Reporting Persons"). This Schedule 13D
relates to the common stock, par value $0.001 per share, of Ligand
Pharmaceuticals Incorporated, a Delaware corporation (the "Company"). Unless the
context otherwise requires, references herein to the "Common Stock" are to such
common stock of the Company. The Management Company is the investment manager or
adviser to a variety of hedge funds and managed accounts (such funds and
accounts, collectively, including but not limited to the Offshore Fund, the
"Funds"). The Funds directly own the Common Stock to which this Schedule 13D
relates, and the Reporting Persons may be deemed to have beneficial ownership
over such Common Stock by virtue of the authority granted to them by the Funds
to vote and to dispose of the securities held by the Funds, including the Common
Stock.

Item 1.  Security and Issuer.

     This statement on Schedule 13D relates to the Common Stock of the Company,
and is being filed pursuant to Rules 13d-1 and 13d-5 under the Securities
Exchange Act of 1934, as amended (the "Exchange Act"). The address of the
principal executive offices of the Company is 10275 Science Center Drive, San
Diego, CA 92121.

Item 2.  Identity and Background.

     (a) This statement is filed by the Reporting Persons. Daniel S. Loeb is the
managing member of the Management Company and controls the Management Company's
business activities. The Management Company is organized as a limited liability
company under the laws of the State of Delaware. The Offshore Fund is organized
as a limited liability exempted company under the laws of the Cayman Islands.

     (b) The address of the principal business and principal office of the
Management Company and Mr. Loeb is 390 Park Avenue, New York, NY 10022. The
address of the principal business and principal office of the Offshore Fund is
c/o Walkers SPV Limited, Walker House, Mary Street, P.O. Box 908GT, George Town,
Grand Cayman, Cayman Islands, British West Indies.

     (c) The principal business of the Management Company is to serve as
investment manager or adviser to the Funds, and to control the investing and
trading in securities of the Funds. The principal business of Mr. Loeb is to act
as the managing member of the Management Company. The principal business of the
Offshore Fund is to invest and trade in securities.

     (d) None of the Reporting Persons, nor, to the best of their knowledge, any
of their directors, executive officers, general partners or members has, during
the last five years, been convicted in a criminal proceeding (excluding traffic
violations or similar misdemeanors).



     (e) None of the Reporting Persons, nor, to the best of their knowledge, any
of their directors, executive officers, general partners or members has, during
the last five years, been a party to a civil proceeding of a judicial or
administrative body of competent jurisdiction and as a result of such proceeding
was or is subject to a judgment, decree or final order enjoining future
violations of, or prohibiting or mandating activities subject to, federal or
state securities laws or finding any violation with respect to such laws.

     (f) Mr. Loeb is a United States citizen.

Item 3.  Source and Amount of Funds or Other Consideration.

     The Funds expended an aggregate of approximately $54,341,445.65 of their
own investment capital to acquire the 7,000,000 shares of Common Stock held by
them and the Offshore Fund expended an aggregate of approximately $35,342,672.96
of its own investment capital to acquire its 4,552,600 shares of Common Stock.
All shares of Common Stock acquired prior to September 7, 2005 were acquired in
open market purchases on the Nasdaq National Market and the shares acquired on
September 7, 2005 or thereafter were acquired on the Pink Sheets and in directly
negotiated transactions with broker-dealer firms.

     The Funds effect purchases of securities primarily through margin accounts
maintained for them with Bear, Stearns Securities Corp. and Goldman, Sachs &
Co., which may extend margin credit to the Funds as and when required to open or
carry positions in the margin accounts, subject to applicable Federal margin
regulations, stock exchange rules and the firm's credit policies. In such
instances, the positions held in the margin accounts are pledged as collateral
security for the repayment of debit balances in the accounts.

Item 4.  Purpose of Transaction.

     On September 13, 2005 the Reporting Persons' beneficial ownership first
exceeded 5% of the Company's outstanding shares of Common Stock.

     The purpose of the acquisition of the shares of Common Stock by the Funds
is for investment. The Reporting Persons may cause the Funds to make further
acquisitions of Common Stock from time to time or to dispose of any or all of
the shares of Common Stock held by the Funds at any time.

     The Reporting Persons are engaged in the investment business. In pursuing
this business, the Reporting Persons analyze the operations, capital structure
and markets of companies, including the Company, on a continuous basis through
analysis of documentation and discussions with knowledgeable industry and market
observers and with representatives of such companies (often at the invitation of
management). From time to time, one or more of the Reporting Persons may hold
discussions with third parties or with management of such companies in which the
Reporting Persons may suggest or take a position with respect to potential
changes in the operations, management or capital structure of such companies as
a means of enhancing shareholder value. Such suggestions or positions may relate
to one or more of the transactions specified in clauses (a) through (j) of Item
4 of Schedule 13D of the Exchange Act, including, without limitation, such
matters as disposing of or selling all or a portion of the



company or acquiring another company or business, changing operating or
marketing strategies, adopting or not adopting certain types of anti-takeover
measures and restructuring the company's capitalization or dividend policy.

     Except as set forth above and in the letter attached hereto as Exhibit 2,
the Reporting Persons do not have any present plans or proposals that relate to
or would result in any of the actions required to be described in Item 4 of
Schedule 13D. Each of the Reporting Persons may, at any time, review or
reconsider its position with respect to the Company and formulate plans or
proposals with respect to any of such matters, but has no present intention of
doing so.

Item 5.  Interest in Securities of the Issuer.

     (a) As of the date of this Schedule 13D, the Management Company
beneficially owns 7,000,000 shares of Common Stock. The Management Company
shares voting and dispositive power over such holdings with Mr. Loeb and with
the Funds. The Shares represent 9.47% of the 73,932,315 shares of Common Stock
outstanding at October 29, 2004, as reported in the Company's last Quarterly
Report on Form 10-Q for the quarterly period ended September 30, 2004.

     As of the date of this Schedule 13D, the Offshore Fund directly
beneficially owns 4,552,600 shares of Common Stock, which represents 6.16% of
the outstanding shares of Common Stock. None of the other individual Funds owns
a number of shares of Common Stock equal to or greater than 5% of such total
Common Stock outstanding.

     (b) The Management Company and Mr. Loeb share voting and dispositive power
over the 7,000,000 shares of Common Stock held directly by the Funds. The
Management Company, Mr. Loeb and the Offshore Fund share voting power and
dispositive power over the 4,552,600 shares of Common Stock held by the Offshore
Fund.

     (c) Schedule A hereto sets forth certain information with respect to
transactions by the Funds, at the direction of the Reporting Persons, in the
Common Stock during the past sixty days.

     Schedule B hereto sets forth certain information with respect to
transactions by the Offshore Fund at the direction of the Management Company and
Mr. Loeb during the past 60 days.

     All shares of Common Stock acquired prior to September 7, 2005 were
acquired in open market purchases on the Nasdaq National Market and the shares
acquired on September 7, 2005 or thereafter were acquired on the Pink Sheets and
in directly negotiated transactions with broker-dealer firms.

     Except as set forth above and on Schedule A and Schedule B, during the last
sixty days there were no transactions in the Common Stock effected by the
Reporting Persons, nor, to the best of their knowledge, any of their directors,
executive officers, general partners or members.


     (d) Other than the Funds which directly hold the shares of Common Stock,
and except as set forth in this Item 5, no person is known to have the right to
receive or the power to direct the receipt of dividends from, or the proceeds
from the sale of, the shares of Common Stock.

     (e) Not applicable.

Item 6.  Contracts, Arrangements, Understandings or Relationships With Respect
         to Securities of the Issuer.

     Pursuant to Rule 13d-1(k) promulgated under the Exchange Act, the Reporting
Persons have entered into an agreement with respect to the joint filing of this
statement, and any amendment or amendments hereto.

     By virtue of the relationships among the Reporting Persons and the Funds,
as described in Item 2, the Reporting Persons and the Funds may be deemed to be
a "group" under the Federal securities laws. Except as otherwise set forth in
this Schedule 13D, each Reporting Person expressly disclaims beneficial
ownership of any of the shares of Common Stock beneficially owned by any other
Reporting Person or the Funds and the filing of this Statement shall not be
construed as an admission, for the purposes of Sections 13(d) and 13(g) or under
any provision of the Exchange Act or the rules promulgated thereunder or for any
other purpose, that any Reporting Person is a beneficial owner of any such
shares.

     Except as set forth herein, there are no contracts, arrangements,
understandings or relationships among the persons named in Item 2 or between
such persons and any other person with respect to any securities of the Company.

Item 7.  Material to be Filed as Exhibits.

          1.   Joint Filing Agreement, dated as of September 23, 2005, by and
               between the Reporting Persons.

          2.   Letter.



                                   Schedule A
                                   ----------

                   (Transactions by the Funds in Common Stock
                           during the past sixty days)


     Date            Transaction            Shares            Price Per Share
     ----            -----------            ------            ---------------

   8/24/05               Buy                332,000               8.0237
   8/25/05               Buy                250,000               8.1479
   8/26/05               Buy                19,500                7.8305
   8/29/05               Buy                198,500               7.9040
   8/30/05               Buy                50,000                7.8660
   8/30/05               Buy                50,000                7.8660
   8/31/05               Buy                100,000               7.8013
    9/1/05               Buy                100,000               7.6944
    9/6/05               Buy                275,000               7.2598
    9/6/05               Buy                275,000               7.2598
    9/6/05               Buy                350,000               7.2596
    9/7/05               Buy                600,000               7.2690
    9/8/05               Buy                210,000               7.6052
    9/8/05               Buy                350,000               7.6120
    9/9/05               Buy                200,000               8.1613
    9/9/05               Buy                25,000                8.0000
   9/12/05               Buy                30,000                8.4143
   9/12/05               Buy                135,000               8.4000
   9/13/05               Buy                800,000               8.0445
   9/13/05               Buy                700,000               8.1213
   9/13/05               Buy                700,000               8.0831
   9/14/05               Buy                235,000               8.0074
   9/14/05               Buy                65,000                8.0564
   9/15/05               Buy                100,000               7.8970
   9/21/05               Buy                200,000               7.2250
   9/22/05               Buy                175,000               7.2793
   9/22/05               Buy                375,000               7.4000
   9/22/05               Buy                100,000               7.4000



                                   Schedule B
                                   ----------

               (Transactions by the Offshore Fund in Common Stock
                           during the past sixty days)


     Date           Transaction                Shares        Price Per Share
     ----           -----------                ------        ---------------

   8/24/05               Buy                  220,500            8.0237
   8/25/05               Buy                  167,000            8.1479
   8/26/05               Buy                  12,300             7.8305
   8/29/05               Buy                  133,500            7.9040
   8/30/05               Buy                  15,000             7.8660
   8/30/05               Buy                  50,000             7.8660
   8/31/05               Buy                  52,600             7.8013
    9/1/05               Buy                  64,400             7.6944
    9/6/05               Buy                  235,100            7.2598
    9/6/05               Buy                  350,000            7.2596
    9/7/05               Buy                  389,600            7.2690
    9/8/05               Buy                  210,000            7.6052
    9/8/05               Buy                  154,000            7.6120
    9/9/05               Buy                  130,000            8.1613
    9/9/05               Buy                  16,100             8.0000
   9/12/05               Buy                  30,000             8.4143
   9/12/05               Buy                  76,900             8.4000
   9/13/05               Buy                  518,900            8.0445
   9/13/05               Buy                  454,700            8.1213
   9/13/05               Buy                  454,700            8.0831
   9/14/05               Buy                  153,900            8.0074
   9/14/05               Buy                  42,200             8.0564
   9/15/05               Buy                  65,000             7.8970
   9/21/05               Buy                  131,400            7.2250
   9/22/05               Buy                  115,900            7.2793
   9/22/05               Buy                  208,900            7.4000
   9/22/05               Buy                  100,000            7.4000



                                   SIGNATURES

     After reasonable inquiry and to the best of our knowledge and belief, the
undersigned certify that the information set forth in this statement is true,
complete and correct.


Dated: September 23, 2005


                                        THIRD POINT LLC



                                        By:  /s/ Daniel S. Loeb
                                            ------------------------------------
                                            Name:  Daniel S. Loeb
                                            Title:  Chief Executive Officer



                     /s/ Daniel S. Loeb
                    ---------------------------------------
                    Daniel S. Loeb

















                         [SIGNATURE PAGE TO SCHEDULE 13D
                                 WITH RESPECT TO
                      LIGAND PHARMACEUTICALS INCORPORATED]