ADVANCED INSTRUCTION TO SELL COMMON STOCK

To: Deutsche Bank Alex. Brown
A Division of Deutsche Bank Securities Inc.

Account Number:

I am a holder of shares, or options to acquire shares, of the common stock ("Common Stock") of Ligand Pharmaceuticals, Inc. (the "Company"). I would like to periodically sell Company shares in order to diversify my portfolio. I also wish to take advantage of Rule 10b5-1 under the Securities Exchange Act of 1934, as amended, which provides for an affirmative defense from insider trading liability for purchases and sales effected pursuant to a contract, instruction or plan entered into when a person is not aware of any material nonpublic information. This instruction ("Instruction") is intended to constitute a "written plan for trading securities" within the meaning of Rule 10b5-1.

I hereby instruct Deutsche Bank Securities Inc. (referred to herein as "Deutsche Bank Alex. Brown") to sell 70,000 shares of Common Stock AND exercise options representing 50,000 shares of Common Stock, and sell the resulting shares of Common Stock pursuant to the specific instructions set forth in Schedules A and B hereto OR as follows:

You are authorized to make deliveries of securities and payment of moneys in accordance with your normal practice. All shares to be sold shall have been previously deposited into my account, and you shall not be required to follow this Instruction if shares are not present in my account (or acceptable arrangements to deliver option shares have not been made) prior to the dates on which sales shall occur. If this Instruction requires you to exercise stock options you shall do so in accordance with your normal procedures, and unless instructed otherwise, remit the exercise price and the withholding tax as calculated by the Company. In no instance should you exercise options that are not in the money. The share amount listed above shall be increased or decreased to reflect stock splits should they occur. I understand that I shall be responsible to arrange for any filings that may be required under applicable law (e.g., Form 144, Schedule 13D, and Forms 4 and 5), and that I may be subject to the short swing profit rules contained in Section 16 of the Securities Exchange Act of 1934. In this connection, I understand that upon my request, you will assist me in making advance arrangements regarding the filing of Forms 144.

All sales shall be effected in your normal fashion in accordance with your terms and conditions for my account and risk. You may act as principal in any transaction hereunder. I understand that you may not be able to make all of the sales contemplated under this Instruction due to a market disruption or a legal, regulatory or contractual restriction applicable to you or any other event or circumstance. I further understand that even in the absence of such a circumstance, you may be unable to make sales consistent with ordinary principles of best execution due to insufficient volume of trading or other market factors in effect on the date of a sale. I hereby ratify and confirm any and all transactions with you in accordance with this Instruction. I also agree to indemnify and hold Deutsche Bank Alex. Brown harmless from and to pay Deutsche Bank Alex. Brown promptly on demand any and all losses arising from its reasonable interpretation and performance of this Instruction.

You will cease making sales under this Instruction as soon as practicable following receipt of written notice from the Company, confirmed by telephone, that the Company has entered into a transaction that results in my being subject to trading restrictions. You shall resume making sales in accordance with this Instruction as soon as practicable after you receive written notice from the Company of the cessation or termination of any such trading restriction. Any sales not made as a result of the imposition of any trading restriction shall be sold in the next following selling period.

While this Instruction is in effect I will not enter into or alter any corresponding or hedging transaction or position with respect to the Common Stock (including any securities convertible or exchangeable into Common Stock). I agree that until this Instruction has been terminated I will not enter into a binding contract with respect to the purchase or sale of Common Stock with another broker, dealer or financial institution, instruct any broker, dealer or financial institution to purchase or sell Common Stock or adopt a trading plan with respect to Common Stock other than this Instruction.

This Instruction may be modified, terminated or amended only by a writing signed by the parties hereto. Any modification or amendment of this Instruction may only occur at a time when I am not aware of material nonpublic information concerning the Company or its securities and I am otherwise permitted to make sales under the Company's insider trading policies. If this Instruction is modified or amended, or if I establish a new plan after termination of this Instruction, no sales shall be made during the thirty (30) calendar days immediately following such modification, amendment or termination (other than sales already provided for in the Instruction prior to modification, amendment or termination).

Deutsche Bank Alex Brown is authorized to begin selling Stock pursuant to this Sales Plan on March 18, 2005, and shall cease selling Stock on the earliest to occur of (i) the date on which Deutsche Bank Alex Brown is required to suspend or terminate sales under the Sales Plan pursuant to the previous paragraph, (ii) the date on which Deutsche Bank Alex Brown receives notice of the death of Seller, (iii) the date on which the Issuer or any other person publicly announces a tender or exchange offer with respect to the Stock or a merger, acquisition, reorganization, recapitalization or comparable transaction affecting the securities of the Issuer as a result of which the Stock is to be exchanged or converted into shares of another company, (iv) the date on which Deutsche Bank Alex Brown receives notice of the commencement or impending commencement of any proceedings in respect of or triggered by Seller's bankruptcy or insolvency and (v) the earlier of

the date that the aggregate number of shares of Stock sold pursuant to this Sales Plan reaches shares specified on Schedules A and B

This Instruction shall not be effective until Deutsche Bank Alex. Brown confirms its acceptance in writing by signing below. It shall remain in full force and effect until revoked or modified by me in writing. Deutsche Bank Alex. Brown may decline to act hereunder upon reasonable notice. I hereby irrevocably authorize you to accept any instruction from the Company to cease or suspend sales hereunder.

/S/ MARK A. RADOVANOVICH                    /S/ DAVID E. ROBINSON
                                            ---------------------
                                            Signature of Customer

MARK A. RADOVANOVICH
Branch Manager
Dated: 12-10-04
Rule10b5 - 1Form.AdvancedInstructionstoSell.12.9.04

/S/ CLIFFORD G. WANG

CLIFFORD G. WANG

--------------------------------------------- -------------------------- -----------------------------
a.                                            b.                         c.
Designated Sale Period                        Authorized Number of       Net Limit Price ($) or
From                     To                   Owned Shares               "Market" Price (select one):
----------------------- --------------------- -------------------------- -----------------------------
June 1, 2005            September 30, 2005    35,000 shares              $15.00/share
----------------------- --------------------- -------------------------- -----------------------------

October 1, 2005         December 31, 2005     35,000 shares              $20.00/share
----------------------- --------------------- -------------------------- -----------------------------


----------------------- --------------------- -------------------------- -----------------------------


----------------------- --------------------- -------------------------- -----------------------------


----------------------- --------------------- -------------------------- -----------------------------


----------------------- --------------------- -------------------------- -----------------------------


----------------------- --------------------- -------------------------- -----------------------------

                                              --------------------
                                              |   70,000 shares  |
                                              --------------------

1. INSTRUCTIONS: In column (a), state the first and last date on which the Shares are authorized to be sold during the Designated Sale Period (Stock sales may occur on or between these dates). The "To" column may be left blank in which case the Designated Sale Period will last until this Instruction terminates.

In column (b), state the maximum number of shares authorized to be sold at the designated price during the Designated Sale Period. Do not aggregate with amounts authorized to be sold at a lower price during the same Designated Sale Period.

In column (c), write either (i) a dollar price which is the minimum price (the "Net Limit Price") at which Stock is authorized to be sold, or
(ii) the word "market" if Stock is to be sold at the then-prevailing market price per share during the Designated Sale Period. If a Net Limit Price is instructed, I understand that my order(s) will be executed only when Deutsche Bank Alex. Brown can sell at a price equal or higher than my minimum price(s) plus the mark-up.

2. I X am (_____ am not) subject to Rule 144 filing requirements and, if applicable, I have provided signed documents to be filed on my behalf.

---------------- ------------ ------------ -------------- ------------ --------------------- ------------------- -------------------
                 a.           b.           c.             d.           e.                    f.                  g.
                                                          Vesting      Designated Sale       Authorized Number   Net Limit Price $
Line             Grant ID #   Date of      Strike         Date For     Period                of Option Shares
                              Grant        Price          Unvested
                                                          Shares       From      To
---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
       1         B92628       3/11/95      $6.75/SHARE    ISO *        3/18/05    3/22/05          15,625        Initiate
                                                          Vested                                                 exercise/sell if at
                                                                                                                 least $.25 above
                                                                                                                 strike price
---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
       2         BM92628      3/22/95      $6.75/SHARE    NQ* Vested   3/18/05    3/22/05          34,375        Initiate
                                                                                                                 exercise/sell  if
                                                                                                                 at least $.25 above
                                                                                                                 strike price
---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
       3

---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
       4

---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
       5

---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
       6

---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
       7

---------------- ------------ ------------ -------------- ------------ ---------- ---------- ------------------- -------------------
*3/22/99                                                                     --------------------
                                                                             |  Total:50,000    |
                                                                             --------------------

INSTRUCTIONS:

1. In columns (a) and (b), list the Options which are to be exercised.

In column (c), specify the applicable strike price.

In column (d) specify the applicable vesting date.

In column (f), state the maximum number of Option Shares to be exercised.

In column (g), write the dollar price which is the minimum price (the "Net Limit Price") at which the Authorized Number of Option Shares is authorized to be sold. If a Net Limit Price is instructed, I understand that my order(s) will be executed only when Deutsche Bank Alex. Brown sells at a price equal or higher than my minimum price(s) plus the mark-up.

2. In the event that Deutsche Bank Alex. Brown is unable to sell the Authorized Number of Option Shares in a Designated Sale Period for any reason: (check one of the following instructions)

X the unsold amount of Option Shares will be carried forward and added to the Authorized Number of Option Shares for each succeeding Designated Sale Period until sold at the original net limit price; or

___ the unsold amount of Option Shares will not be sold and will not be carried over to the next Designated Sale Period.

3. I X am (_____ am not) subject to Rule 144 filing requirements and, if applicable, I have provided signed documents to be filed on my behalf.

I recognize that if the nature of the above listed options changes materially, including but not limited to my termination, I will notify Deutsche Bank Alex. Brown immediately.

Client's name: ANDRES NEGRO-VILAR
Issuer's name: LIGAND PHARMACEUTICALS
Type of securities: STOCK OPTION
Maximum Number of Shares
to sell under plan ______________
Maximum Number of Emploee Stock
Options to sell under the plan: 130,000

I, ANDRES NEGRO-VILAR, as of the date below, establish this Sales Plan ("the Plan") in order to sell shares of the Issuer's common stock pursuant to the requirements of Rule 10b5-1 under the Securities Exchange Act of 1934, as amended (the "Exchange Act").

I request that Merrill Lynch, Pierce, Fenner & Smith Incorporated ("Merrill Lynch") execute the Plan as follows:

1. Starting on January 10, 2005 and ending on December 31, 2005,

a. For securities other than employee stock options, SELL:

[ ] __________ [number] of shares every_________[time period: day, week, month, quarter, day/date of month, ect.], provided the price per share is at or above $__________ [dollar amount] on the principal exchange or market on which the shares are traded (the "Exchange").

[ ] shares pursuant to the attached table;

Carry forward provision (optional)

[ ] Any shares not sold in a given _________ [time period: day, week, month, quarter, day/date of month, ect.], because the parameters (E.G., specified sale price) under the ---- Plan were not met, will carry forward to future _______ [time periods] until sold.

b. For employee stock options, EXERCISE MY OPTIONS AND SELL THE UNDERLYING SHARES:

[ ] ___________ [number] stock options every__________ [time period: day, week, month, quarter, day/date of month, etc.], provided the price per underlying share is at or above $________
[dollar amount] on the principal exchange or market on which the shares are traded (the "Exchange")

Carry forward provision (optional)

[ ] Any options not exercised and underlying shares not sold in a given _________ [time period: day, week, month, quarter, day/date of month, ect.], because the parameters (e.g., specified sale price) under the Plan were not met, will carry forward to future _______ [time periods] until sold.

(i) Merrill Lynch will exercise no stock option, unless its exercise price is less than the market price of the underlying share; and Merrill Lynch first will exercise those stock options {SELECT ONE}:

[ ] with the earliest expiration date

[ ] with the lowest exercise price; and

(ii) Merrill Lynch may deduct from the proceeds of each stock option exercised and the underlying shares sold the sum of
(a) the exercise price and (b) any withholding tax and then remit that sum to the Issuer.

2. SUSPENSION

If Merrill Lynch must suspend sales allocated under the Plan, pursuant to Section 1 above, on a particular day for any of the following reasons:

a. a day specified by the Plan is not a day on which the shares trade regular way on the Exchange;

b. trading of the shares on the Exchange is suspended for any reason;

c. there is insufficient demand for any or all of the shares at or above the specified price; (e.g., specified price met but all shares could not be sold at or above specified price)

d. Merrill Lynch cannot effect a sale of shares due to legal, regulatory or contractual restrictions applicable to it or to me (including without limitation, Regulation M); or

then, shares allocated under the Plan for sale during the period when sales under the Plan are suspended {SELECT ONE ONLY} :

[ ] will remain unsold

[X] will be sold as soon as possible provided specified parameters are met

[ ] will be carried forward to be sold with the next amount of shares to be sold in accordance with Section 1 of the Plan

3. TERMINATION

The Plan shall end on the earliest of:

a. the termination date listed above;

b. the completion of all sales contemplated in Section 1 of the Plan;

c. my or Merrill Lynch's reasonable determination that:

(i) the Plan does not comply with Rule 10b5-1 or other applicable securities laws;

(ii) I have not, or Merrill Lynch has not, complied with the Plan, Rule 10b5-1 or other applicable securities laws; or

(iii) I have made misstatements in my Client Representations to Merrill Lynch;

[ ] the filing of a bankruptcy petition by the Issuer or Client

[ ] the public announcement of a merger, recapitalization, acquisition, tender or exchange offer, or other business combination or reorganization .

[ ] the public announcement of a public offering of securities by the Issuer

[ ] the conversion of the shares into rights to receive fixed amounts of cash or into debt securities and/or preferred stock

[ ] my severance or retirement from the Issuer or

[X] receipt by Merrill Lynch of written notice of termination from me pursuant to Section 13 below.

4. At the discretion of Merrill Lynch, shares allocated under the Plan for sale on a given day or date may be sold in bulk or in smaller increments, depending upon market demand and the minimum price established in Section 1.

5. In the event of a stock split or reverse stock split, the share quantity and dollar amount at which shares are sold will be automatically adjusted proportionately.

6. Unless I have indicated otherwise in Section 2 above, in the event of a reincorporation or other corporate reorganization resulting in an automatic share-for-share exchange of new shares for the type of shares subject to the Plan, then the new shares will automatically replace the type of shares originally specified in the Plan.

7. Compliance with Rule 144 and Rule 145

a. I understand and agree that if I am an affiliate or control person for purposes of Rule 144 under the Securities Act of 1933, as amended (the "Securities Act"), or if the securities subject to the Plan are restricted securities subject to limitations under Rule 144 or eligible for resale under Rule 145, then all sales of securities under the Plan will be in accordance with the applicable provisions of Rule
144. I request and authorize Merrill Lynch to complete and file on my behalf the Forms 144 (pre-signed by me) necessary to affect the Plan, if any.

b. If appropriate, I understand and agree that upon my prompt signature and delivery to Merrill Lynch of Form 144, Merrill Lynch will make one Form 144 filing at the beginning of each three-month period, commencing with the date of the first sale made in connection with the Plan, and that each Form 144 shall state the following: "This proposed sale is made pursuant to a plan intended to comply with Rule 10b5-1(c), previously adopted on [insert plan adoption date], when I was not aware of material nonpublic information".

c. Merrill Lynch will conduct sales pursuant to Rule 144 or Rule 145 if appropriate, including applying Rule 144 volume limitations as if the sales under the Plan were the only sales subject to the volume limitations.

d. I agree not to take any action or to cause any other person or entity to take any action that would require me to aggregate sales of securities pursuant to Rule

8. Indemnification

a. I agree to indemnify and hold harmless Merrill Lynch from and against all claims, losses, damages and liabilities arising out of inquiries and/or proceedings resulting from assertions that:

(i) the Plan or sales made under the Plan do not comply with Rule 10b5-1 or with state securities laws or regulations prohibiting trading while in possession of material nonpublic information and

(ii) Merrill Lynch has not executed any sales pursuant to the provisions of the Plan.

b. This indemnification will survive termination of the Plan.

9. In consideration of Merrill Lynch accepting orders to sell securities under this Plan, I make the following representations, warranties and covenants:

a. I established the Plan in good faith, in compliance with the requirements of Rule 10b5-1, and at a time when I was not aware of material nonpublic information about the Issuer, whose securities are the subject of the Plan.

b. I have consulted with legal counsel and other advisors in connection with my decision to enter into the Plan and have confirmed that the Plan meets the criteria set forth in Rule 10b5-1.

c. I own all shares that are subject to the Plan free and clear of liens or encumbrances of any kind (except for shares underlying employee stock options).

d. Except as provided in the Plan and while the Plan is in effect, I confirm that:

(i) I will not engage in offsetting or hedging transactions in violation of Rule10b5-1; and

(ii) I will notify Merrill Lynch in advance of any sales or purchases of, or derivative transactions on, any of the Issuer's securities.

e. I further confirm my understanding that while this Plan is in effect, I may not disclose to the persons at Merrill Lynch effecting sales under the Plan for me any information concerning the Issuer that might influence the execution of the Plan.

(i) The Plan does not violate the Issuer's insider trading policies.

(ii) I have informed the Issuer of the existence and provisions of the Plan, and, if necessary under the Issuer's insider-trading policies, authorized representatives of the Issuer have approved the Plan and have been provided with a copy of the plan.

g. I agree to make or cause to be made all necessary filings, including Rule 144 filings, filings pursuant to Section 13 and Section 16 of the Exchange Act, and any other filings necessary pursuant to the Securities Act and/or the Exchange Act.

h. Delivery requirements

(i) FOR SECURITIES OTHER THAN EMPLOYEE STOCK OPTIONS, prior to the date of execution of any sales specified under the Plan, I agree to have delivered into the custody of Merrill Lynch certificates representing that number of securities that may be sold pursuant to the Plan (or other appropriate evidence thereof), together with all transfer documents and other authorizations required for Merrill Lynch to effect settlement of sales of such securities on my behalf.

(ii) FOR EMPLOYEE STOCK OPTIONS, (a) the number of options granted to me by the Issuer that are vested, exercisable and registered is equal to or greater than the number of options to be exercised and the underlying shares to be sold under the Plan and (b) I agree to provide to Merrill Lynch all necessary documentation, properly executed, to effect the timely exercise of the stock option and the subsequent sale and settlement of the securities.

(iii) I agree that Merrill Lynch's obligation to execute sales under the Plan is conditioned on the satisfaction of the foregoing delivery requirements

i. I agree to inform Merrill Lynch as soon as possible of (a) any subsequent restrictions imposed on me due to changes in the securities (or other) laws or of any contractual restrictions imposed on the Issuer that would prevent Merrill Lynch or me from complying with the Plan and (b) the occurrence of any event as set forth in the Plan that would cause the Plan to end or be suspended under Section 2 or Section 3 of the Plan.

10. The Plan may be modified or amended only upon:

a. the written agreement of myself and Merrill Lynch and

11. The Plan may be signed in counterparts, each of which will be an original.

12. The Plan, including the representations, warranties and covenants in Section 9, constitutes the entire agreement between me and Merrill Lynch and supersedes any prior agreements or understandings regarding the Plan.

13. All notices given by the parties under this Plan will be as follows:

a. If to Merrill Lynch:

Managing Director and Administrative Manager Merrill Lynch, Pierce, Fenner & Smith, Inc. 1650 Market Street
29th Floor
Philadelphia, PA 19103

b. If to me: [client address].

Ligand Pharmaceuticals
10275 Science Center Drive
San Diego, CA 92121

IF YOU ARE SUBJECT TO THE REPORTING REQUIREMENTS OF SECTION 16 OF THE EXCHANGE ACT, COMPLETE THE FOLLOWING SECTION 14 TO HAVE TRANSACTION INFORMATION FOR OPEN MARKET TRANSACTIONS UNDER THE PLAN FORWARDED TO A DESIGNATED THIRD PARTY.

14. I authorize Merrill Lynch to transmit transaction information via fax and/or email for open window and transactions under the Plan (sales and purchases) to:

a.      Name:BARBARA OLSON              b. Name: WARNER BROADDUS
        Title:LEGAL                     Title:GENERAL COUNSEL
        Organization: LIGAND PHARM.     Organization: LIGAND PHARM.
        Fax:858-550-5632                Fax Number: 858-550-1825
        Tel.:858-550-7577               Tel.:858-550-7830
        e-mail:bolson@ligand.com        e-mail:wbroaddus@ligand.com

Reasonable efforts will be made to transmit transaction information for open market transactions under the Plan (purchase or sale) by the close of business on the day of the purchase or sale, but no later than the close of business on the first trading day following the purchase or sale. I acknowledge that Merrill Lynch: (1) has no obligation to confirm receipt of any email or faxed information by the designated contact and (2)

15. This Plan will be governed by and construed in accordance with the internal laws of the State of New York.

By:    /S/ ANDRES NEGRO VILAR
Name:  Andres Negro-Vilar
Date:  December 10, 2004

Acknowledged and Agreed this10th day of December, 2004:

Merrill Lynch, Pierce, Fenner & Smith Incorporated

By:    /S/ BRIAN P. PUGH
Name:  Brian Pugh
Title: Administrative Manager

----------------- --------------- ------------------- --------------- ----------------- ---------------
                                  NUMBER OF OPTIONS
                                  TO BE SOLD IN THE      GRANT NO.                         SALE PRICE
     START DATE       END DATE           PLAN            GRANT DATE     EXERCISE PRICE      -LIMIT"
----------------- --------------- ------------------- --------------- ----------------- ---------------
1/10/2005         12/31/2005      5,625               B93903          ISO  $7.625       At or above
                                                                                        $18.00
----------------- --------------- ------------------- --------------- ----------------- ---------------
1/10/2005         12/31/2005      24,375              BM93903         NQ $7.625         At or above
                                                                                        $18.00
----------------- --------------- ------------------- --------------- ----------------- ---------------
1/10/2005         12/31/2005      32,988              B92947          ISO $12.125       At or above
                                                                                        $25.00
----------------- --------------- ------------------- --------------- ----------------- ---------------
1/10/2005         12/31/2005      67,012              BM92947         NQ $12.125        At or above
                                                                                        $30.00
----------------- --------------- ------------------- --------------- ----------------- ---------------

----------------- --------------- ------------------- --------------- ----------------- ---------------

----------------- --------------- ------------------- --------------- ----------------- ---------------

----------------- --------------- ------------------- --------------- ----------------- ---------------
    TOTAL                         130,000
----------------- --------------- ------------------- --------------- ----------------- ---------------