SECOND AMENDMENT TO LEASE

Exhibit 10.1

SECOND AMENDMENT TO LEASE

     THIS SECOND AMENDMENT TO LEASE (“ Second Amendment ”) is made and entered into as of the 25th day of September, 2009, by and between DMH CAMPUS INVESTORS, LLC, a Delaware limited liability company (“ Landlord ”) and NEUROCRINE BIOSCIENCES, INC., a Delaware corporation (“ Tenant ”).

R E C I T A L S :

     A. Landlord and Tenant entered into that certain Lease dated as of December 4, 2007 (the “ Original Lease ”), as amended by that certain First Amendment to Lease dated as of December 10, 2008 by and between Landlord and Tenant (“ First Amendment ”), whereby Landlord leased to Tenant and Tenant leased from Tenant in those certain buildings located and addressed at 12780 El Camino Real (herein referred to as the “ Rear Building ”) and 12790 El Camino Real (herein referred to as the “ Front Building ”), San Diego, California (collectively, the “ Buildings ”). The Original Lease, as amended by the First Amendment, may be referred to herein as the “ Lease .”

     B. By this Second Amendment, Landlord and Tenant desire to modify the Lease as provided herein.

     C. Unless otherwise defined herein, capitalized terms as used herein shall have the same meanings as given thereto in the Lease.

     NOW, THEREFORE, in consideration of the foregoing recitals and the mutual covenants contained herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties hereto hereby agree as follows:

A G R E E M E N T :

     1.  The Premises . Landlord and Tenant hereby agree that pursuant to the Lease, Landlord currently leases to Tenant and Tenant currently leases from Landlord the interior of Buildings (the “ Premises ”), all as more particularly described in the Lease. The purpose of this Amendment is to provide for the release of the Front Building from the Premises with the intent that Landlord will then market and lease the rentable space in the Front Building under direct leases with third party tenants; therefore, Paragraph 2 of the First Amendment is hereby deleted.

     2.  Tenant’s Initial Release Payment . Concurrently with Tenant’s execution and delivery of this Second Amendment to Landlord (the “ Release Date ”), Tenant shall pay to Landlord an amount equal to Four Million Dollars ($4,000,000.00) (“ Initial Release Payment ”) and, upon such payment, the Premises constituting the Front Building shall no longer be part of the Premises and Tenant shall be released from all of its rights and obligations under the Lease pertaining to the Front Building except as expressly provided herein and except for Tenant’s indemnity obligations under the Lease for occurrences prior to the Release Date pertaining to the Front Building which, by their terms, expressly survive the expiration or sooner termination of the Lease pertaining to the Front Building. Tenant’s payment of the Initial Release Payment shall satisfy Tenant’s obligations in Section 3b. of the First Amendment. Upon the Release Date, the definition of “Premises” for all purposes under the Lease, as amended, shall be the interior of the Rear Building only.

     3.  Tenant’s Continuing Rent Obligations . In addition to the Initial Release Payment and without limiting Tenant’s monetary and non-monetary obligations with respect to the Rear Building, Tenant shall pay to Landlord Monthly Rental for the Rear Building in the following amounts:

In addition to the above Monthly Rental payments, Tenant shall pay Additional Rental based upon the square footage of the Front Building and Rear Building combined through July 31, 2011 (i.e., Tenant’s Pro Rata Share will be based on both buildings even though Tenant is only leasing the Rear Building) and Tenant’s failure to do so shall be deemed a default by Tenant under the Lease for the Rear Building (entitling Landlord to exercise all of its rights and remedies under the Lease, at law and in equity). Notwithstanding the fact that the square footage of the Front Building is used to calculate Tenant’s Additional Rental, such square footage number is used solely to calculate Additional Rental, and the Front Building will no longer be a part of the “Premises” as of the Release Date and Tenant will not have any liabilities, duties or obligations associated with the Front Building (except as provided in Section 2 above). Accordingly, Section 3.c and the last sentence of Paragraph 6 of the First Amendment are hereby deleted.

     4.  Rent Differential Amount Payments . Landlord and Tenant acknowledge and agree that an amount equal to Three Million Two Hundred Eighty Thousand Dollars ($3,280,000.00) is stipulated by Landlord and Tenant to represent fifty percent (50%) of the difference between (i) Tenant’s total rent payments (including Monthly Rental, Additional Rental and all other sums required to by paid by Tenant) for the Front Building from and after August 1, 2011 and for the remainder of the Term (until the December 1, 2019 scheduled Expiration Date) and (ii) the estimated rent payments that Landlord anticipates Landlord will receive from prospective tenants for lease of space in the Front Building from and after August 1, 2011 and for the remainder of the Term (until the December 1, 2019 scheduled Expiration Date) (the “ Rent Differential Amount ”). The outstanding balance of the Rent Differential Amount shall bear interest at the rate of seven and one-half percent (7.5%) per annum commencing as of August 1, 2011. Tenant shall pay as additional rent under the Lease and without offset, setoff or deduction, such Rent Differential Amount to Landlord in the stipulated monthly installments set forth in Schedule “1” attached hereto commencing on August 1, 2011 (payable at the same time and in the same manner as Monthly Rental is due and payable by Tenant under the Lease) for the remainder of the initial Lease Term commencing as of August 1, 2011 and continuing until the scheduled December 1, 2019 Expiration Date (the “ Rent Differential Monthly Payment Amount ”). Landlord and Tenant acknowledge and agree that the Rent Differential Monthly Payment Amount is the monthly amount stipulated by Landlord and Tenant equal to fifty percent (50%) of the difference between Tenant’s total monthly rent payment (including Monthly Rental, Additional Rental and all other sums required to by paid by Tenant) for the Front Building and the estimated monthly rent payments (including base rent, additional rent and all other sums) that Landlord anticipates Landlord will receive from prospective tenants for leases of space in the Front Building from August 1, 2011 until the scheduled Expiration Date discounted at seven and one-half percent (7.5%) to arrive at a net present value amount. As such, Landlord and Tenant acknowledge and agree such Rent Differential Monthly Payment Amount constitutes fifty percent (50%) of the monthly amount discounted at seven and one-half percent (7.5%) to arrive at a net present value amount that would otherwise be payable by Tenant under the Lease for the Front Building, with the remaining fifty percent (50%) amount which is not part of the Rent Differential Monthly Payment Amount to be forgiven by Landlord and referred to herein as “ Monthly Rent Differential Forgiveness Amount .” Notwithstanding anything above to the contrary, in the event Tenant is in monetary default under the Lease, as modified by this Second Amendment (beyond the expiration of all applicable notice and cure periods) at any time that an outstanding balance exists of the Rent Differential Amount, then the Monthly Rent Differential Forgiveness Amount that was forgiven by Landlord shall be deemed reinstated and Tenant shall pay the Monthly Rent Differential Forgiveness Amounts to Landlord upon ten (10) days prior written notice from Landlord, which notice may be sent by Landlord to Tenant any time after Tenant is in monetary default under the Lease (beyond the expiration of all applicable notice and cure periods) even if such default is subsequently cured by Tenant. In addition, in the event of a default by Tenant under Sections 13.1(d), (f), (g) or (h) of the Original Lease or any default that results in termination of the Lease, then (and without limiting Landlord’s other rights and

remedies, at law and/or in equity), the entire Monthly Rent Differential Forgiveness Amount for the entire Term of the Lease shall be deemed to be included as rent in Landlord’s claim for damages under the Lease. Notwithstanding anything above to the contrary, Tenant shall have the right, upon at least thirty (30) days prior written notice to Landlord, to prepay the then entire Rent Differential Amount to Landlord at any time after the August 1, 2011, with the prepayment amounts set forth in Schedule “1” attached hereto. In calculating the present value of the Rent Differential Amount, a seven and one-half (7.5%) discount rate shall be utilized. In addition, effective as of the date hereof, Tenant shall, within ten (10) days of Landlord’s written request, pay to Landlord fifty percent (50%) of any and all tenant improvement costs incurred by Landlord in connection with any and all new leases and lease amendments for space in the Front Building previously not leased to a third party (i.e., Tenant’s obligation is limited to subsidizing the tenant improvements for the first lease or amendment applicable to the space in the Front Building, and Tenant will have no obligation to pay for any tenant improvements for any subsequent lease or amendment of the same space in the Front Building after the initial lease or amendment of such space) greater than Sixty-Five Dollars ($65.00) per rentable square feet of the space leased under any such lease or lease amendment; provided, however, that any tenant improvement costs in excess of One Hundred Dollars ($100.00) per square foot of the premises of any such new lease or lease amendment shall require Tenant’s approval (in Tenant’s sole and absolute (but good faith) discretion). Tenant’s obligations under Sections 3 and 4 of this Second Amendment are in lieu of Tenant’s obligations in Section 3a. of the First Amendment, which is hereby deleted.

     5.  Landlord’s Renovations . Tenant acknowledges that Landlord may from time to time, at Landlord’s sole option, renovate, improve, alter, or modify (collectively, the “ Renovations ”) the Project, including without limitation, the Common Areas, systems and equipment, roof, and structural portions of the same, as well as the possible construction of an additional building in the Project. Tenant agrees to use its best efforts to cooperate with Landlord in connection with such Renovations. Tenant hereby agrees that such Renovations and Landlord’s actions in connection with such Renovations (including any construction noise) shall in no way constitute a constructive eviction of Tenant nor entitle Tenant to any abatement of Monthly Rental; provided, however, Landlord agrees to use commercially reasonable efforts to minimize material interference with Tenant’s use of and access to the Premises as a result of such Renovations. Landlord shall have no responsibility or for any reason be liable to Tenant for any direct or indirect injury to or interference with Tenant’s business arising from the Renovations, nor shall Tenant be entitled to any compensation or damages from Landlord for loss of the use of the whole or any part of the Premises or of Tenant’s personal property or improvements resulting from the Renovations or Landlord’s actions in connection with such Renovations, or for any inconvenience or annoyance oc