COMMENTS

Exhibit 10.2f

This Fifth Lease Amendment (this “Fifth Amendment”), made effective as of the 1^st day of October, 2009 (the “Amendment Date”), by and between Wake Forest University Health Sciences, a North Carolina non-profit corporation having its principal office in Winston-Salem, North Carolina (“Landlord”), and Targacept, Inc., a Delaware corporation having its principal office in Winston-Salem, North Carolina (“Tenant”), amends that certain Lease effective August 1, 2002, as amended by the First Lease Amendment effective January 1, 2005, the Second Lease Amendment effective March 31, 2006, the Third Lease Amendment effective January 1, 2007 and the Fourth Lease Amendment effective August 1, 2007 (the “Lease”).

WITNESSETH:

WHEREAS, pursuant to paragraphs 6.2.1 and 6.2.2 of the Lease, Landlord agreed to provide the 2007 Upfitting Funding and to recover the amount thereof, with interest, through an increase to the rental rate payable by Tenant under the Lease over a specified period; and

WHEREAS Landlord and Tenant desire to amend the Lease to decrease the rental rate payable by Tenant thereunder to reflect a reduction in the interest rate applicable to the 2007 Upfitting Funding;

NOW, THEREFORE, for and in consideration of the premises, of the rents reserved and to be paid by Tenant to Landlord, and of the additional mutual covenants of the parties, Landlord and Tenant hereby agree as follows:

“If the Lease terminates upon expiration of the Renewal Term (not, for clarity, the Second Renewal Term), the amount payable to Landlord will be $658,085.71, provided that all installments of Rent have been timely paid. A schedule depicting the amortization of the 2007 Upfitting Funding (based upon a 7% interest rate from October 1, 2009) is attached to the Lease as Exhibit D.”;

2

IN WITNESS WHEREOF, Landlord and Tenant have caused this Fifth Amendment to be executed, pursuant to authority duly granted, effective as of the Amendment Date.

3

Attachment I

MONTHLY ADJUSTMENT

Interest Rate Applicable to 2007

Upfitting Funding