LEASE TERMINATION AND WARRANT PURCHASE AGREEMENT

Exhibit 10.1

LEASE TERMINATION AND WARRANT PURCHASE AGREEMENT

THIS LEASE TERMINATION AND WARRANT PURCHASE AGREEMENT (this “ Agreement ”) is entered into as of this 18th day of September, 2009, by and between BMR-201 INDUSTRIAL ROAD LLC, a Delaware limited liability company (“ Landlord ”), BIOMED REALTY, L.P., a Maryland limited partnership (“ BioMed ”), and ARCA BIOPHARMA, INC., a Delaware corporation (f.k.a., Nuvelo, Inc., “ Tenant ”).

RECITALS

A. WHEREAS, Landlord and Tenant entered into that certain that certain Lease dated as of January 11, 2005, as amended by that certain First Amendment to Lease dated as of May 10, 2005 and that certain Second Amendment to Lease dated as of February 23, 2006 (collectively, and as the same may have been further amended, supplemented or otherwise modified from time to time, the “ Lease ”), whereby Tenant leases certain premises (the “ Premises ”) from Landlord at 201 Industrial Road in San Carlos, California;

B. WHEREAS, Tenant, as sublandlord, and Bernard Hodes Group, Inc., a Delaware corporation (“ BHG ”), as subtenant, entered into that certain Sublease dated as of January 17, 2008 (the “ BHG Sublease ”), for a portion of the Premises (such portion, the “ BHG Premises ”), and Landlord consented to the BHG Sublease pursuant to that certain Consent to Sublease dated as of January 17, 2008 (the “ BHG Consent ”), by and among Landlord, Tenant and BHG;

C. WHEREAS, Landlord, Tenant and BHG intend to modify the BHG Sublease and BHG Consent by entering into that certain First Amendment to Sublease of even date herewith (the “ Sublease Amendment ”); and

D. WHEREAS, Landlord and Tenant desire to terminate the Lease and, in connection therewith, Tenant shall issue to BioMed and BioMed shall purchase a warrant (the “ Warrant ”) to purchase shares of common stock of Tenant in accordance with the following provisions.

AGREEMENT

NOW, THEREFORE, the parties hereto, in consideration of the mutual promises, representations, warranties and covenants contained herein and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, and intending to be legally bound, agree as follows:

1. Termination . Subject to the satisfaction of all of the terms conditions herein, Landlord and Tenant hereby terminate the Lease as of September 18, 2009 (the “ Termination Date ”). As of the Termination Date, the Lease shall be fully and finally surrendered and terminated and shall no longer be of any force or effect, except for those provisions that, by their express terms, survive the expiration or earlier termination thereof.

2. Termination Consideration . Landlord and Tenant acknowledge that Tenant’s Termination Option (as set forth in Section 4.6 of the Lease) is subject to Tenant’s satisfaction of certain conditions, including without limitation Tenant’s payment of any unamortized tenant improvements and leasing commissions. Landlord and Tenant further acknowledge that the early termination of the Lease will result in certain losses and liabilities for Landlord (including, without limitation, loss of income; negative impact on Landlord’s ability to sell, finance or refinance the Property; and increased costs associated with securing a replacement tenant(s)). Accordingly, the following (“ Termination Consideration ”) shall be full, fair and reasonable consideration in exchange for Landlord’s agreement to terminate the Lease prior to its natural expiration:

a. Termination Payment . Within one (1) business day after the mutual execution and delivery of this Agreement, Tenant shall pay Landlord immediately available funds that total Three Million Four Hundred Thirty-One Thousand One Hundred Eighty-One and 23/100s Dollars ($3,431,181.23);

b. Security Deposit . Landlord and Tenant acknowledge that Landlord holds cash in the amount of Four Hundred Eighty-Nine Thousand Six Hundred Twenty-Three Dollars ($489,623) (“ Security Deposit ”). Notwithstanding anything to the contrary in the Lease, Landlord is immediately entitled to the entire amount of the Security Deposit without the need for notice to Tenant or affording Tenant, or any other party, an opportunity to cure. In addition, Landlord shall remain entitled to draw on the Security Deposit for any other purpose set forth in the Lease or this Agreement;

c. Warrant . Tenant shall, within thirty (30) days after full execution and delivery of this Agreement (the “ Warrant Issuance Date ”), deliver to BioMed, and BioMed shall purchase from Tenant, the Warrant, in the form attached hereto as Exhibit A for a purchase price of Ten Dollars ($10). BioMed hereby acknowledges, agrees to and affirms that (i) all representations and warranties set forth in Section 4 of the Warrant are true and correct in all respects as of the date hereof and shall be true and correct in all respects as of the Warrant Issuance Date, and (ii) Tenant shall have no obligation to execute and deliver the Warrant unless all representations and warranties set forth in Section 4 of the Warrant are true and correct in all respects as of the date hereof and as of the Warrant Issuance Date.

d. Assignment of BHG Sublease . Effective as of the Termination Date, Tenant hereby assigns to Landlord all of its right, title and interest as “Sublandlord” under the BHG Sublease, and commencing as of the Termination Date subject to the Sublease Amendment, Landlord hereby accepts such assignment and assumes the performance of all obligations of Tenant as “Sublandlord” under the BHG Sublease, as such lease may be further modified by Landlord and BHG.

3. Release of Liability .

a. By Tenant . Tenant hereby fully and unconditionally releases, cancels, annuls, rescinds, discharges, disclaims, waives and releases any and all rights and benefits it may have under the Lease or BHG Consent, any right to inspect Landlord’s records for Taxes and Operating Costs, any claims of credit for overpaid Rent (including Operating Costs) or any other

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amounts paid to Landlord, and the right to collect any amounts under the BHG Sublease arising from and after the Termination Date. Tenant acknowledges that as of the Termination Date, Landlord shall have the right to collect any amounts due to Tenant under the BHG Sublease as if Landlord was “Sublandlord” (as defined in the BHG Sublease), without obligation or liability to Tenant and without obligation or liability to BHG for prepaid rent or security deposit under the BHG Sublease.

b. By Landlord . Subject to Tenant’s compliance with those terms that survive the expiration or termination of the Lease, Landlord hereby fully and unconditionally releases, cancels, annuls, rescinds, discharges, disclaims, waives and releases any and all rights and benefits it may have under the Lease or BHG Consent and any right to claim any future payment for adjustments to Monthly Rent and Operating Costs. Landlord acknowledges that as of the Termination Date, subject to the Sublease Amendment, Landlord shall have the rights, and obligations to perform, of Tenant under the BHG Sublease, as such lease may be further modified by Landlord and BHG.

4. Indemnification . Tenant shall protect, defend, indemnify, release, save and hold Landlord and each of Landlord’s officers, directors, successors, affiliates, employees, agents, consultants and lenders (each, an “ Indemnified Party ”) harmless from and against any and all Losses (as defined below) imposed upon or incurred by or asserted against such Indemnified Party and directly or indirectly arising out of or in any way relating to (a) the inaccuracy of any representation of Tenant herein, or (b) Tenant’s failure to perform or comply with any obligations or covenants (i) prior to the Termination Date (A) of Tenant under the Lease, (B) of “Sublandlord” under the BHG Sublease or (C) otherwise as set forth in the Lease, BHG Sublease or the BHG Consent, including, without limitation, any failure to refund pre-paid rent or security deposit to BHG, or (ii) after the Termination Date of Tenant pursuant to this Agreement (including, without limitation, with respect to provisions of the Lease that expressly survive the expiration or earlier termination thereof). As used herein, the term “ Losses ” includes any and all claims, suits, liabilities, actions, proceedings, obligations, debts, damages, losses, costs, expenses, diminutions in value, fines, penalties, charges, liens, fees, expenses, judgments, awards, amounts paid in settlement, punitive damages and foreseeable and unforeseeable consequential damages of whatever kind or nature (including, without limitation, attorneys’ fees and other costs of defense).

5. Quitclaim . To the extent, if any, that the Lease gives Tenant any right, title or interest in or to the Premises, Tenant does, effective as of the Termination Date, hereby remise, release and quitclaim to Landlord such right, title or interest in or to the Premises and shall execute and deliver to Landlord any documentation reasonably requested by Landlord to effect or document such remise, release and quitclaim.

6. Condition of Premises . On or prior to the Termination Date, Tenant shall surrender the Premises to Landlord in the condition required under the Lease.

7. FF&E . Tenant hereby conveys all right, title and interest to all furniture, fixtures and equipment (“ FF&E ”) located in the Premises as of the date hereof, and represents to Landlord that none of the FF&E has been or will be damaged, modified or removed from the

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Premises. If requested by Landlord, Tenant shall execute and deliver to Landlord a separate bill of sale covering the FF&E in form and substance reasonably acceptable to Landlord and Tenant.

8. Representations of Parties . Each of Landlord and Tenant represents that it has not made any assignment, sublease (other than the BHG Sublease), transfer, conveyance or other disposition of the Lease or any interest therein, nor made or entered into any agreement that would result in any mechanic’s lien or other claim, demand, obligation, liability, action or cause of action arising from or with respect to the Lease or the Premises. Tenant hereby represents and warrants to Landlord that, with respect to the BHG Sublease, (a) BHG has not prepaid more than one (1) month’s rent (i.e., beyond rent paid for September, 2009), (b) Tenant will promptly return to BHG any security deposit or other security in connection with the BHG Sublease, and (c) to Tenant’s knowledge, there are no defaults, or conditions existing that with the passage of time may become a default, whether on behalf of Landlord, Tenant, or BHG under the BHG Sublease or BHG Consent.

9. Miscellaneous .

a. Voluntary Agreement . The parties have read this Agreement and the mutual releases contained in it, and have freely and voluntarily entered into this Agreement.

b. Attorneys’ Fees . If any party commences an action against the other party arising out of or in connection with this Agreement (other than the Warrant), the prevailing party shall be entitled to recover from the losing party reasonable attorneys’ fees and costs of suit.

c. Successors . This Agreement shall be binding on and inure to the benefit of the parties and their successors and assigns.

d. Counterparts . This Agreement may be executed in one or more counterparts that, when taken together, shall constitute one original.

e. Defined Terms . Capitalized terms not otherwise defined herein shall have the meanings given them in the Lease.

f. Amendment . This Agreement (but excluding the Warrant) may only be amended or modified by written agreement between the parties.

g. Applicable Law . This Agreement (but excluding the Warrant) shall be governed by and construed in accordance with the laws of the State, or Commonwealth, in which the Premises are located applicable to contracts made and to be performed State, or Commonwealth, in which the Premises are located, without regard to conflict of law principles.

h. Conflict . In the event of any conflict or discrepancy between the provisions of this Agreement (but excluding the Warrant) and the provisions of the Lease, BHG Sublease or Sublease Consent, or any other document between the parties (but excluding the Warrant), the provisions of this Agreement shall control.

i. Entire Agreement . This Agreement, the Sublease Amendment and the Warrant set forth the entire understanding of the parties relating to the transaction contemplated

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hereby, and supersede all prior understandings, whether written or oral. There are no obligations, commitments, representations or warranties relating to them except those expressly set forth in this Agreement, the Sublease Amendment and the Warrant.

j. Binding Agreement . This Agreement shall be binding upon and inure to the benefit of the parties and their successors, assigns, parents, subsidiaries, divisions and affiliates.

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IN WITNESS WHEREOF, the parties have executed this Lease Termination Agreement as of the day hereinabove first written.

EXHIBIT A

WARRANT

THIS WARRANT AND THE SECURITIES ISSUABLE UPON EXERCISE HEREOF HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “ SECURITIES ACT ”), OR ANY STATE SECURITIES LAW, AND MAY NOT BE SOLD, TRANSFERRED, ASSIGNED, PLEDGED, HYPOTHECATED OR OTHERWISE DISPOSED OF OR EXERCISED UNLESS (I) A REGISTRATION STATEMENT REGISTERING SUCH SECURITIES UNDER THE SECURITIES ACT AND APPLICABLE STATE SECURITIES LAWS SHALL HAVE BECOME EFFECTIVE, OR (II) THE CORPORATION HAS RECEIVED AN OPINION OF COUNSEL SATISFACTORY TO IT THAT SUCH TRANSFER MAY LAWFULLY BE MADE WITHOUT REGISTRATION UNDER THE SECURITIES ACT OR QUALIFICATION UNDER APPLICABLE STATE