Exhibit 10.4

THIRD AMENDMENT TO LEASE

1.            PARTIES

1.1           THIS AGREEMENT made the 30th day of September, 2011 is between 101 HUDSON LEASING ASSOCIATES (“Landlord”) whose address is c/o Mack-Cali Realty Corporation, 343 Thornall Street, P.O. 7817, Edison, NJ 08818-7817 and OPTIMER PHARMACEUTICALS, INC. (“Tenant”), whose address is 10110 Sorrento Valley Road, Suite C, San Diego, California 92121.

2.            STATEMENT OF FACTS

2.1           Landlord and Tenant have previously entered into a Lease Agreement dated February 9, 2011, as amended by a First Amendment to Lease dated May 4, 2011 and a Second Amendment to Lease dated July 5, 2011 (hereinafter collectively referred to as the “Lease”) covering 14,196 gross rentable square feet on the thirty-fifth (35th) floor (“Existing Premises”) in the building located at 101 Hudson Street, Jersey City, New Jersey (“Building”); and

2.2           The Term of the Lease expires on June 30, 2016 (“Expiration Date”); and

2.3           Tenant desires to expand the Existing Premises by leasing 10,141 gross rentable square feet on the thirty-sixth (36th) floor of the Building (“Expansion Premises”), as shown on Exhibit A attached hereto and made a part hereof; and

2.4           The parties desire to extend the Term of the Lease for a period to commence on July 1, 2016; and

2.5           The parties desire to amend certain terms of the Lease as set forth below.

3.            AGREEMENT

NOW, THEREFORE, in consideration of the terms, covenants and conditions hereinafter set forth, Landlord and Tenant agree as follows:

3.1           The above recitals are incorporated herein by reference.

3.2           All capitalized and non-capitalized terms used in this Agreement which are not separately defined herein but are defined in the Lease shall have the meaning given to any such term in the Lease.

3.3           The Term applicable to the Expansion Premises shall commence on the Effective Date (as defined below) and shall terminate at 11:59 p.m. on the last day of the month during which the day prior to the six (6) year and two (2) month anniversary of the Effective Date occurs (the “New Expiration Date”).

3.4           The effective date applicable to the Expansion Premises (the “Effective Date”) shall be the earlier of (i) the day Landlord substantially completes the improvements to be made to the Expansion Premises in accordance with Exhibit B attached hereto and made part hereof and Landlord has received all necessary inspection sign-offs to allow Tenant to legally occupy the Expansion Premises or (ii) the date Tenant or anyone claiming under or through Tenant shall occupy the Expansion Premises. The estimated Effective Date is the target substantial completion date shown in the project schedule attached as Exhibit C.

3.5           From and after the Effective Date, the following shall be effective:

a.             Landlord shall lease to Tenant and Tenant shall hire from Landlord the Expansion Premises as shown on Exhibit A attached hereto and made part hereof.

d.             The “Demised Premises”, “demised premises” and “Premises” shall be defined as 24,337 gross rentable square feet consisting of 14,196 gross rentable square feet on the thirty-fifth (35th) floor and 10,141 gross rentable square feet on the thirty-sixth (36th) floor of the Building and the Lease shall be deemed amended accordingly.

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c.             In addition to the Basic Annual Rent payable applicable to the Existing Premises, Tenant shall pay Landlord Basic Annual Rent applicable to the Expansion Premises which shall accrue as follows and paragraph (h) of the Reference Page to the Lease shall be deemed amended accordingly:

Notwithstanding the foregoing, provided that this Lease is in full force and effect and Tenant is not in default beyond any applicable notice and cure period, Tenant shall have no obligation to pay the Monthly Installments of Basic Annual Rent applicable to the Expansion Premises for the first (1st) and second (2nd) full calendar months of the Term applicable to the Expansion Premises. Tenant shall remain liable for the Monthly Installments of Basic Annual Rent with respect to the Existing Premises for such months.

If the Effective Date is a day other than the first day of a calendar month, then the Monthly Installment of Basic Annual Rent payable by Tenant for such month shall be prorated at the same rental rate payable for the first (1st) Monthly Installment listed above.

d.             Tenant’s Tax Share applicable to the Expansion Premises shall be .84% and paragraph (i) of the Reference Page to the Lease shall be deemed supplemented accordingly. Tenant’s Expense Share applicable to the Expansion Premises shall be .87% and paragraph (k) of the Reference Page to the Lease shall be deemed supplemented accordingly.

e.             Tenant shall pay to Landlord as Additional Rent Tenant’s Tax Share and Tenant’s Expense Share applicable to the Expansion Premises of the cost to Landlord for each of the categories set forth in Article 3 Additional Rent of the Lease above the current Base Tax Year and Base Operating Year, as applicable. Tenant shall continue to pay Landlord Tenant’s Tax Share and Tenant’s Expense Share applicable to the Existing Premises of Taxes and Operating Expenses pursuant to Article 3 of the Lease.

f.              Tenant’s Electricity Share for the Expansion Premises shall be deemed to be 33% and Paragraph (q) of the Reference Page to the Lease shall be deemed supplemented accordingly and Tenant shall pay its Electric Share applicable to the Expansion Premises in accordance with Article 4 Electricity of the Lease. Tenant’s Electricity Share for the Existing Premises shall remain unchanged and Tenant shall pay the cost of electricity consumed within the demised premises in accordance with Article 4 Electricity of the Lease.

g.             Tenant’s Chilled Water Share for the Expansion Premises shall be deemed to be 33% and Paragraph (u) of the Reference Page to the Lease shall be deemed supplemented accordingly and Tenant shall pay its Chilled Water Share applicable to the Expansion Premises in accordance with Article 21 Services and Equipment of the Lease. Tenant’s Chilled Water Share for the Existing Premises shall remain unchanged and Tenant shall pay the cost of chilled water consumed within the demised premises in accordance with Article 21 Services and Equipment of the Lease.

h.             The number of Tenant’s Vehicles shall be increased to sixteen (16) and Paragraph (o) of the Reference Page to the Lease shall be deemed amended accordingly.

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This Agreement may be executed in multiple counterparts, each of which, when assembled to include an original signature for each party contemplated to sign this Agreement, will constitute a complete and fully executed original. All such fully executed counterparts will collectively constitute a single agreement. Tenant expressly agrees that if the signature of Landlord and/or Tenant on this Agreement is not an original, but is a digital, mechanical or electronic reproduction (such as, but not limited to, a photocopy, fax, e-mail, PDF, Adobe image, JPEG, telegram, telex or telecopy), then such digital, mechanical or electronic reproduction shall be as enforceable, valid and binding as, and the legal equivalent to, an authentic and traditional ink-on-paper original wet signature penned manually by its signatory.

IN WITNESS WHEREOF, Landlord and Tenant have hereunto set their hands and seals the date and year first above written, and acknowledge one to the other that they possess the requisite authority to enter into this transaction and to sign this Agreement.

LANDLORD:

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EXHIBIT B

LANDLORD’S WORK

NOTES

RE: Workletter Agreement for office space on the 36th floor at 101 Hudson Street, Jersey City, New Jersey.

September 30, 2011

TENANT:

OPTIMER PHARMACEUTICALS, INC.

You (“Tenant”) and we (“Landlord”) are executing a written lease amendment (“Amendment”), covering the space referred to above, as more particularly described in the Amendment (“Premises”).

With respect to the construction work being conducted in or about the Expansion Premises, each party agrees to be bound by the approval and actions of their respective construction representatives. Unless changed by written notification, the parties hereby designate the following individuals as their respective construction representatives:

To induce Tenant to enter into the Agreement (which together with the Lease are hereby incorporated by reference) and in consideration of the covenants hereinafter contained, Landlord and Tenant mutually agree as follows:

1.                         Landlord, at its sole cost and expense, shall have its architect prepare the following architectural and mechanical drawings and specifications based upon the sketch layout supplied to Landlord by Tenant, attached hereto and made a part hereof, upon full execution of this Lease.

a.                             Architectural drawings and specifications for Tenant’s partition layout, reflected ceiling, placement of electrical outlets and other installations for the work to be done by Landlord.

b.                            Mechanical plans and specifications where necessary for installation of air conditioning systems, ductwork and heating.

All such plans and specifications are expressly subject to Landlord’s written approval, which Landlord covenants it will not unreasonably withhold.

2.                         Landlord agrees to cause the partition plan, electrical plan, HVAC zoning plan and the reflected ceiling plan to be delivered to Tenant on or before the fifteenth (15th) day after Tenant’s approved sketch layout. Tenant agrees to approve said plans by initialing and returning same to Landlord within five (5) business days of receipt of each plan. Upon approval of the plans initialed by Tenant, Landlord shall file said plans with the appropriate governmental agencies.

3.                         Landlord agrees, at its sole cost and expense and without charge to Tenant (unless otherwise provided), to do the work in the Expansion Premises as shown on the plans attached hereto and described on the “Description of Materials” schedule attached hereto which shall hereinafter be referred to as “The Work”. The Work shall include any and all costs to install necessary public corridors and demising walls as necessary and as shown in Exhibit A Floor Plan. The Work shall include Landlord’s general conditions and overhead amounts indicated

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on the Description of Materials. “Building Standard” shall mean the type and grade of material, equipment and/or device designated by Landlord as standard for the Building. All items are Building Standard unless otherwise noted. The provisions of Article 6 of the Lease shall apply to any alterations made to the Expansion Premises after the initial work to be performed herein. Landlord shall deliver the Expansion Premises to Tenant on the Effective Date with all building systems servicing the Expansion Premises in proper working order. Landlord shall warranty that the Work be free of defects for a period of one (1) year from the Effective Date, except to the extent any portion of the Work is damaged or becomes defective as a result of any misuse or neglect by Tenant.

4.                             Intentionally omitted.

5.                             All low partitioning, workstation modules, bank screen partitions and prefabricated partition systems shall be furnished and installed by Tenant.

6.                             The installation or wiring of telephone and computer (data) outlets is not part of The Work. Tenant shall bear the responsibility to provide its own telephone and data systems at Tenant’s sole cost and expense. Upon expiration or sooner termination of the Lease, Tenant shall remove all telephone and data equipment from the Expansion Premises upon vacation of same. Notwithstanding the foregoing, Tenant shall not be required to remove any of its wiring at the expiration or earlier termination of the Lease.

7.                             Changes in The Work, if necessary or requested by the Tenant, shall be accomplished after submission of Tenant’s final approved sketch layout, , by written agreement between Landlord and Tenant hereinafter referred to as a Change Order and without invalidating any part of the Lease or Workletter Agreement. Each Change Order shall be prepared by Landlord and signed by both Tenant and Landlord stating their agreement upon all of the following:

a.                                       The scope of the change in The Work; and

b.                                      The cost of the change; and

c.                                       Manner in which the cost will be paid or credited; and

d.                                      The estimated extent of any adjustment to the Effective Date (if any) as a result of the change in The Work.

Each and every Change Order shall be signed by Landlord’s and Tenant’s respective construction representatives. In no event shall any Change Order(s) be permitted without such authorizations. A 7.5% supervision plus 7.5% overhead charge will be added to the cost of any Change Order and to the cost of any other work to be performed by Landlord in the Expansion Premises after Landlord’s completion of The Work. If Tenant shall fail to approve any such Change Order within one (1) week, the same shall be deemed disapproved in all respects by Tenant and Landlord shall not be authorized to proceed thereon. Any increase in the cost of The Work or the change in The Work stated in a Change Order which results from Tenant’s failure to timely approve and return said Change Order shall be paid by the Tenant. Tenant agrees to pay to Landlord the cost of any Change Order promptly upon receipt of an invoice for same.

8.                             If Tenant elects to use the architect suggested by Landlord, this architect becomes the Tenant’s agent solely with respect to the plans, specifications and The Work. If any change is made after completion of schematic drawings and prior to completion of final construction documents which result in a Change Order and additional costs, such costs shall be the responsibility of the Tenant.

9.                             Ten (10) business days prior to Tenant’s occupancy of the Expansion Premises, Tenant shall be provided the opportunity by Landlord to identify and list any portion of The Work which does not conform to this Workletter Agreement (“Punch List”). The Landlord shall review with the Tenant all of the items so listed and correct or complete any portion of The Work which fails to conform to the requirements of this Workletter Agreement.

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10.                   The terms contained in the Agreement (which include all exhibits attached thereto) constitute Landlord’s agreement with Tenant with respect to the work to be performed by Landlord on Tenant’s behalf. If the architectural drawings are in conflict with the terms of the Agreement, then the Lease shall be deemed the controlling document.

11.                   All materials and installations constructed for the Tenant within the Expansion Premises shall become the property of the Landlord upon installation. No refund, credit or removal of said items is to be permitted at the termination of the Lease. Items installed that are not integrated in any such way with other common building materials do not fall under this provision (e.g. shelving, furniture, etc.).

12.                   It is agreed that notwithstanding the date provided in the Lease for the Effective Date, the term applicable to the Expansion Premises shall not commence until Landlord has “substantially completed” all work to be performed by Landlord in the Expansion Premises as hereinbefore set forth in Paragraph 3 above and as set forth in the Amendment; provided, however, that if Landlord shall be delayed in substantially completing said work as a result of:

a.                          Tenant’s failure to approve the plans and specifications in accordance with Paragraph 2 hereof; or

b.                         Tenant’s failure to furnish interior finish specifications, i.e., paint colors, carpet selection, etc., to Landlord by the fifth (5th) working day after Landlord has approved the plans and specifications submitted by Tenant referred to in Paragraph 2 hereof; or

c.                          Tenant’s request for materials, finishes or installations other than Landlord’s Building Standard; or

d.                         Tenant’s changes in The Work; or

e.                          The performance of a person, firm, partnership or corporation employed by Tenant and the completion of the said work by said person, firm, partnership or corporation;

then the Effective Date of the term of said Lease shall be accelerated by the number of days of such delay and Tenant’s obligation to pay Basic Annual Rent and Additional Rent shall commence as of such earlier date.

13.                   Landlord shall permit Tenant and its agents to enter the Expansion Premises at least two (2) weeks prior to the Effective Date in order that Tenant may perform through its own non-union contractors (or union contractor if required by Landlord) such other work and decorations as Tenant may desire at the same time Landlord’s contractors are working in the Expansion Premises. The foregoing license to enter prior to the Effective Date, however, is conditioned upon:

a.                          Tenant’s workmen and mechanics working in harmony and not interfering with the labor employed by Landlord, Landlord’s mechanics or contractors or by any other Tenant or its mechanics or contractors; and

b.                         Tenant providing Landlord with evidence of Tenant’s contractors and subcontractors carrying such worker’s compensation, general liability, personal and property insurance as required by law and in amounts no less than the amounts set forth in Article 9 of the Lease. If at any time such entry shall cause disharmony or interference therewith, this license may be withdrawn by Landlord upon forty-eight (48) hours written notice to Tenant. Such entry shall be deemed controlled by all of the terms, covenants, provisions and conditions of said Lease, except as to the covenant to pay Basic Annual Rent and Additional Rent. Except in the event of Landlord, its agents or employees gross negligence or intentional misconduct, Landlord shall not be liable in any way for any injury, loss or damage which may occur to any of Tenant’s decorations or installations so made prior to the Effective Date, the same being solely at Tenant’s risk.

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14.                     No part of the Expansion Premises shall be deemed unavailable for occupancy by the Tenant, nor shall any work which the Landlord is obligated to perform in such part of the Expansion Premises be deemed incomplete for the purpose of any adjustment of Basic Annual Rent payable hereunder, solely due to the non-completion of details of construction, decoration or mechanical adjustments which are minor in character and the non-completion of which does not materially interfere with the Tenant’s beneficial use and occupancy of such part of the Expansion Premises.

15.                     Tenant is responsible for all costs related to the repairs and maintenance of any additional or supplemental HVAC systems, appliances and equipment installed to meet Tenant’s specific requirements. Tenant shall purchase a service contract for this equipment so that the equipment is covered by such service contract each year of the term of the Lease and shall forward a copy of such contract to Landlord.

16.                     If construction is to occur in a space occupied by Tenant’s employees, Tenant shall be liable for all costs associated with a delay if Tenant shall fail to comply with a submitted construction schedule to relocate personnel, furniture, or equipment. Tenant shall relocate such personnel, furniture and equipment at its sole cost and expense. In the event Tenant fails to comply with a submitted construction schedule following notice thereof by Landlord, and to the extent. Landlord’s contractors are delayed as a result thereof, Tenant shall be responsible for the costs, which shall include, but not be limited to the following:

a.                           reasonable and actual cost of construction workers time wasted (upon reasonable evidence thereof); and

b.                          reasonable and actual cost of any overtime work necessary to meet schedule deadlines; and

17.                     This workletter is based on the quantities and specifications listed herein. Any change to these specifications shall require the recalculation of the construction costs. Such recalculation shall not negate any other section of this Lease.

18.                     All sums payable by Tenant to Landlord in connection with this Exhibit B and any other work to be performed by Landlord within the Expansion Premises and billable to Tenant shall be deemed Additional Rent.

-END-

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EXHIBIT B

09/26/11

Worldetter Agreement between Lessor/Landlord and Lessee/Tenant for the construction of the Premises in the Building. The costs for the work stated below are based upon the Description of Materials attached which enumerates the materials and quantities estimated for the Work.

DESCRIPTION OF MATERIALS

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EXHIBIT B

09/26/11

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EXHIBIT B