SECOND AMENDMENT TO LOAN AND SECURITY AGREEMENT

Exhibit 10.29

SECOND AMENDMENT TO

LOAN AND SECURITY AGREEMENT

THIS SECOND AMENDMENT TO LOAN AND SECURITY AGREEMENT (this “Agreement”) is dated as of September [    ], 2011, by and among REGADO BIOSCIENCES, INC., a Delaware corporation (“Borrower”). MIDCAP FINANCIAL SBIC, LP, a Delaware limited partnership in its capacity as agent (“Agent”) for the lenders under the Loan Agreement (as defined below) (“Lenders”), and the Lenders.

W I T N E S S E T H:

WHEREAS, Borrower, Lenders and Agent are parties to that certain Loan and Security Agreement, dated as of May 25, 2011, and as amended by that certain First Amendment to Loan and Security Agreement, dated as of August 1, 2011 (as so amended and as may be further amended, restated, supplemented or otherwise modified from time to time, the “Loan Agreement”; capitalized terms used herein have the meanings given to them in the Loan Agreement except as otherwise expressly defined herein), pursuant to which Lenders have agreed to provide to Borrower certain loans and other extensions of credit in accordance with the terms and conditions thereof; and

WHEREAS, Borrower, Agent and Lenders desire to amend certain provisions of the Loan Agreement in accordance with, and subject to, the terms and conditions set forth herein.

NOW, THEREFORE, in consideration of the premises, the covenants and agreements contained herein, and other good and valuable consideration, the receipt and adequacy of which are hereby acknowledged, Borrower, Lenders and Agent hereby agree as follows:

1. Acknowledgment of Obligations. Borrower hereby acknowledges, confirms and agrees that all Term Loans made prior to the date hereof, together with interest accrued and accruing thereon, and fees, costs, expenses and other charges owing by Borrower to Agent and Lenders under the Loan Agreement and the other Debt Documents, are unconditionally owing by Borrower to Agent and Lenders, without offset, defense or counterclaim of any kind, nature or description whatsoever except as may be limited by applicable bankruptcy, insolvency, reorganization, moratorium or other similar laws relating to or affecting creditor’s rights generally.

2. Amendments to Loan Agreement. Subject to the terms and conditions of this Agreement, including, without limitation, the conditions to effectiveness set forth in Section 5 below, the Agent and Lenders hereby agree that the Loan Agreement shall be amended as follows:

(a) Section 2.2(d) of the Loan Agreement is hereby amended by deleting such section in its entirety and by inserting, in lieu thereof, the following:

“(d) Permitted Prepayment of Loans. Borrower shall have the option to prepay the Term Loans advanced by the Lenders under this Agreement, in whole or in part, provided,

however, that Borrower (i) provides written notice to Agent of its election to prepay a portion or the entire amount of Term Loans at least fifteen (15) days prior to such prepayment, and (ii) (X) in the case of a prepayment of the entire amount of Term Loans, pays to Agent, for payment to each Lender in accordance with its respective Pro Rata Share, on the date of such prepayment an amount equal to the sum of: (A) all outstanding principal of the Term Loans and all other Obligations, and all accrued interest thereon. plus (B) the Final Payment, plus (C) the Prepayment Fee, plus (D) all other sums that shall have become due and payable, including Lenders’ Expenses and (y) in the case of a prepayment of a portion of the Term Loans, pays to each Lender in accordance with its respective Pro Rata Share, on the date of such prepayment an amount equal to the sum of: (A) the amount of the outstanding principal of the Term Loans prepaid and all accrued interest thereon, plus (B) the Partial Final Payment, plus (C) the Partial Prepayment Fee, plus (D) all other sums that shall have become due and payable, including Lenders’ Expenses.”

(b) Section 14 of the Loan Agreement is hereby amended by deleting the definitions of “Final Payment” and “Prepayment Fee” in their entirety and substituting in lieu thereof the following new definitions to read in their entirety as follows:

““Final Payment” means a payment (in addition to and not a substitution for the regular monthly payments of principal plus accrued interest) due on the earlier to occur of (a) the Maturity Date, (b) the acceleration of any Term Loan, and (c) the prepayment of a Term Loan pursuant to Section 2.2(c) or (d), equal to the amounts advanced by Lenders pursuant to the Term Loan Commitments multiplied by the Final Payment Percentage less any Partial Final Payment fee paid pursuant to Section 2.2(d).

“Prepayment Fee” means with respect to any Term Loan subject to prepayment prior to the Maturity Date, whether by mandatory or voluntary prepayment, acceleration or otherwise, an additional fee payable to the Lenders in an amount equal to:

(a) for a prepayment made on or after the Closing Date through and including the date which is twelve (12) months after the Closing Date, two percent (2.0%) multiplied by the original Term Loan Commitments, less any Partial Prepayment Fee paid in accordance with Section 2.2(d); and

(b) for a prepayment made after the date which is more than twelve (12) months after the Closing Date and prior to the Maturity Date, one percent (1.0%) multiplied by the original Term Loan Commitments, less any Partial Prepayment Fee paid in accordance with Section 2.2(d).”

(c) Section 14 of the Loan Agreement is hereby amended by inserting the following new definitions in proper alphabetical order:

““Partial Final Payment” means a payment (in addition to and not a substitution for the regular monthly payments of accrued interest plus, if applicable, principal) due on the prepayment of a portion of the Term Loan pursuant to Section 2.2(d), equal to the amount of the Term Loans so prepaid multiplied by the Final Payment Percentage.

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“Partial Prepayment Fee” means with respect to any Term Loan subject to prepayment prior to the Maturity Date, by voluntary prepayment paid pursuant to Section 2.2(d), an additional fee payable to the Lenders in an amount equal to:

(a) for a prepayment made on or after the Closing Date through and including the date which is twelve (12) months after the Closing Date, two percent (2.0%) multiplied by the amount of the outstanding principal of the Term Loans prepaid; and

(b) for a prepayment made after the date which is more than twelve (12) months after the Closing Date and prior to the Maturity Date, one percent (1.0%) multiplied by the amount of the outstanding principal of the Term Loans prepaid.”

3. No Other Amendments. Except for the amendments and agreements set forth and referred to in Section 2 above, the Loan Agreement and the other Debt Documents shall remain unchanged and in full force and effect. Nothing in this Agreement is intended, or shall be construed, to constitute a novation or an accord and satisfaction of any of Borrower’s Obligations or to modify, affect or impair the perfection or continuity of Agent’s security interests in, security titles to or other liens, for the benefit of itself and the Lenders, on any Collateral for the Obligations.

4. Representations and Warranties. To induce Agent and Lenders to enter into this Agreement. Borrower does hereby warrant, represent and covenant to Agent and Lenders that (i) each representation or warranty of Borrower set forth in the Loan Agreement is hereby restated and reaffirmed as true and correct in all material respects on and as of the date hereof as if such representation or warranty were made on and as of the date hereof (except to the extent that any such representation or warranty expressly relates to a prior specific date or period), (ii) no Default or Event of Default has occurred and is continuing as of the date hereof and (iii) Borrower has the power and is duly authorized to enter into, deliver and perform this Agreement and this Agreement is the legal, valid and binding obligation of Borrower enforceable against Borrower in accordance with its terms.

5. Condition Precedent to Effectiveness of this Agreement. This Agreement shall become effective as of the date (the “Amendment Effective Date”) upon which Agent shall notify Borrower in writing that Agent has received one or more counterparts of this Agreement duly executed and delivered by Borrower. Agent and Lenders, in form and substance satisfactory to Agent and Lenders.

6. Release.

(a) In consideration of the agreements of Agent and Lenders contained herein and for other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, Borrower, on behalf of itself and its successors, assigns, and other legal representatives, hereby absolutely, unconditionally and irrevocably releases, remises and forever discharges Agent and each Lender and their respective successors and assigns, and their respective present and former shareholders, affiliates, subsidiaries, divisions, predecessors, directors, officers, attorneys, employees, agents and other representatives (Agent, Lenders and all

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such other persons being hereinafter referred to collectively as the “Releasees” and individually as a “Releasee”), of and from all demands, actions, causes of action, suits, covenants, contracts, controversies, agreements, promises, sums of money, accounts, bills, reckonings, damages and any and all other claims, counterclaims, defenses, rights of set-off, demands and liabilities whatsoever (individually, a “Claim” and collectively, “Claims”) of every name and nature, known or unknown, suspected or unsuspected, both at law and in equity, which Borrower or any of its successors, assigns, or other legal representatives may now or hereafter own, hold, have or claim to have against the Releasees or any of them for, upon, or by reason of any circumstance, action, cause or thing whatsoever which arises at any time on or prior to the Amendment Effective Date, including, without limitation, for or on account of, or in relation to, or in any way in connection with the Loan Agreement or any of the other Debt Documents or transactions thereunder or related thereto.

(b) Borrower understands, acknowledges and agrees that its release set forth above may be pleaded as a full and complete defense and may be used as a basis for an injunction against any action, suit or other proceeding which may be instituted, prosecuted or attempted in breach of the provisions of such release.

(c) Borrower agrees that no fact, event, circumstance, evidence or transaction which could now be asserted or which may hereafter be discovered shall affect in any manner the final, absolute and unconditional nature of the release set forth above.

7. Covenant Not To Sue. Borrower, on behalf of itself and its successors, assigns, and other legal representatives, hereby absolutely, unconditionally and irrevocably, covenants and agrees with and in favor of each Releasee that it will not sue (at law, in equity, in any regulatory proceeding or otherwise) any Releasee on the basis of any Claim released, remised and discharged by Borrower pursuant to Section 6 above. If Borrower or any of its successors, assigns or other legal representatives violates the foregoing covenant. Borrower, for itself and its successors, assigns and legal representatives, agrees to pay, in addition to such other damages as any Releasee may sustain as a result of such violation, all attorneys’ fees and costs incurred by any Releasee as a result of such violation.

8. Advice of Counsel. Each of the parties represents to each other party hereto that it has discussed this Agreement with its counsel.

9. Severability of Provisions. In case any provision of or obligation under this Agreement shall be invalid, illegal or unenforceable in any applicable jurisdiction, the validity, legality and enforceability of the remaining provisions or obligations, or of such provision or obligation in any other jurisdiction, shall not in any way be affected or impaired thereby.

10. Counterparts. This Agreement may be executed in multiple counterparts, each of which shall be deemed to be an original and all of which when taken together shall constitute one and the same instrument.

11. GOVERNING LAW. THIS AGREEMENT SHALL BE GOVERNED BY, AND CONSTRUED IN ACCORDANCE WITH, THE INTERNAL LAWS OF THE STATE OF MARYLAND APPLICABLE TO CONTRACTS MADE AND PERFORMED IN SUCH

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IN WITNESS WHEREOF, the parties hereto have caused this Second Amendment to Loan and Security Agreement to be duly executed and delivered as of the day and year specified at the beginning hereof.

REGADO BIOSCIENCES, INC

SECOND AMENDMENT TO LOAN AND SECURITY AGREEMENT

SIGNATURE PAGE

REGADO BIOSCIENCES, INC

SECOND AMENDMENT TO LOAN AND SECURITY AGREEMENT

SIGNATURE PAGE