Exhibit 10.1

FIRST AMENDMENT

TO

LOAN AND SECURITY AGREEMENT

This First Amendment to Loan and Security Agreement (the “Amendment”), is
entered into as of April 29, 2011, by and between SQUARE 1 BANK (the “Bank”) and
LIGAND PHARMACEUTICALS INCORPORATED (the “Borrower”).

RECITALS

Borrower and Bank are parties to that certain Loan and Security Agreement dated
as of March 31, 2011 (as amended from time to time, the “Agreement”). The
parties desire to amend the Agreement in accordance with the terms of this
Amendment.

NOW, THEREFORE, the parties agree as follows:

 

1) Section 6.3 of the Agreement is hereby amended and restated, in its entirety,
as follows:

6.3 Cash Security Account. Borrower shall at all times maintain the Cash
Security Account, with a balance of Cash in such Cash Security Account at all
times of not less than $10,000,000.

 

2) The following definitions in Exhibit A to the Agreement are hereby amended
and restated, in their entirety, as follows:

“Cash Security Account” means segregated Certificate of Deposit, account No.
60100378, held at Bank as collateral for Borrower’s Obligations, in a minimum
amount of $10,000,000.

“Collateral” means Cash in the amount of at least $10,000,000 held in the Cash
Security Account and pledged to Bank as security for the Obligations.

“Revolving Line” means 1 or more Credit Extensions in an aggregate amount of up
to $10,000,000.

 

3) Unless otherwise defined, all initially capitalized terms in this Amendment
shall be as defined in the Agreement. The Agreement, as amended hereby, shall be
and remain in full force and effect in accordance with its respective terms and
hereby is ratified and confirmed in all respects. Except as expressly set forth
herein, the execution, delivery, and performance of this Amendment shall not
operate as a waiver of, or as an amendment of, any right, power, or remedy of
Bank under the Agreement, as in effect prior to the date hereof. Borrower
ratifies and reaffirms the continuing effectiveness of all agreements entered
into in connection with the Agreement.

 

4) Borrower represents and warrants that the representations and warranties
contained in the Agreement

are true and correct as of the date of this Amendment.

 

5) This Amendment may be executed in two or more counterparts, each of which
shall be deemed an

original, but all of which together shall constitute one instrument.

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6) As a condition to the effectiveness of this Amendment, Bank shall have
received, in form and substance satisfactory to Bank, the following:

 

  a) this Amendment, duly executed by Borrower;

 

  b) payment of a $7,500 facility fee, which may be debited from any of
Borrower’s accounts;

 

  c) an officer’s certificate of Borrower with respect to incumbency and
resolutions authorizing the execution of this Amendment;

 

  d) payment of all Bank Expenses, including Bank’s expenses for the
documentation of this Amendment and any related documents, which may be debited
from any of Borrower’s accounts; and

 

  e) such other documents and completion of such other matters, as Bank may
reasonably deem necessary or appropriate.

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IN WITNESS WHEREOF, the undersigned have executed this Amendment as of the first
date above written.

 

0000000000 0000000000 LIGAND PHARMACEUTICALS
INCORPORATED       SQUARE 1 BANK

By: /s/ John Sharp                                                 

      By: /s/ Zack Robbins                                         Name: John
Sharp                                                        Name: Zack
Robbins                                        

Title: CFO                                                             

      Title: AVP                                                         

[Signature Page to First Amendment to Loan and Security Agreement]