Table of Contents As filed with the Securities and Exchange Commission on February 22, 2005 Registration No. 333-115538 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 AMENDMENT NO. 6 TO FORM S-1 REGISTRATION STATEMENT Under The Securities Act of 1933 TARGACEPT, INC. (Exact name of registrant as specified in its charter) Delaware 2834 56-2020050 (State or other jurisdiction (Primary Standard Industrial (I.R.S. Employer of incorporation or organization) Classification Code Number) Identification Number) 200 East First Street, Suite 300 Winston-Salem, North Carolina 27101 (336) 480-2100 (Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices) J. Donald deBethizy Chief Executive Officer Targacept, Inc. 200 East First Street, Suite 300 Winston-Salem, North Carolina 27101 (336) 480-2100 (Name, address, including zip code, and telephone number, including area code, of agent for service) Copies to: Jonathan L. Kravetz, Esq. Jeffrey C. Howland, Esq. Peter A. Zorn, Esq. David E. Redlick, Esq. Megan N. Gates, Esq. Womble Carlyle Targacept, Inc. Stuart R. Nayman, Esq. Mintz, Levin, Cohn, Ferris, Sandridge & Rice, PLLC 200 East First Street, Wilmer Cutler Pickering Glovsky and Popeo, P.C. One West Fourth Street Suite 300 Hale and Dorr LLP One Financial Center Winston-Salem, Winston-Salem, 399 Park Avenue Boston, Massachusetts 02111 North Carolina 27101 North Carolina 27101 New York, New York 10022 (617) 542-6000 (336) 721-3516 (336) 480-2115 (212) 937-7200 Approximate date of commencement of proposed sale of the securities to the public: As soon as practicable after the effective date of this Registration Statement. If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under the Securities Act of 1933, as amended (the “Securities Act”), check the following box. ☐ If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐ If this Form is a post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier registration statement for the same offering. ☐ If this Form is a post-effective amendment filed pursuant to Rule 462(d) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier registration statement for the same offering. ☐ If delivery of the Prospectus is expected to be made pursuant to Rule 434, please check the following box. ☐ The Registrant hereby amends this Registration Statement on such date or dates as may be necessary to delay its effective date until the Registrant shall file a further amendment which specifically states that this Registration Statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act or until the Registration Statement shall become effective on such date as the Commission, acting pursuant to said Section 8(a), may determine. Table of Contents The information in this preliminary prospectus is not complete and may be changed. We may not sell these securities until the registration statement filed with the Securities and Exchange Commission is declared effective. This preliminary prospectus is not an offer to sell these securities and it is not soliciting an offer to buy these securities in any state where the offer or sale is not permitted. Subject to Completion, Dated February 22, 2005 6,250,000 Shares Common Stock This is the initial public offering of Targacept, Inc. We are offering 6,250,000 shares of our common stock. We anticipate that the initial public offering price will be between $11.00 and $13.00 per share. Our common stock has been approved for listing on the NASDAQ National Market under the symbol “TRGT.” Investing in our common stock involves risk. See “ Risk Factors” beginning on page 8. Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities or passed upon the adequacy or accuracy of this prospectus. Any representation to the contrary is a criminal offense. Underwriting Price to Discounts and Proceeds to Public Commissions Targacept Per Share $ $ $ Total $ $ $ We have granted the underwriters the right to purchase up to 937,500 additional shares of common stock to cover over-allotments. Deutsche Bank Securities Pacific Growth Equities, LLC CIBC World Markets Lazard The date of this prospectus is , 2005 Table of Contents PROSPECTUS SUMMARY The following summary highlights information appearing elsewhere in this prospectus. It may not contain all of the information that may be important to you in deciding whether to invest in our common stock. You should read the entire prospectus carefully, including the “Risk Factors” section and the financial statements and related notes appearing at the end of this prospectus, before making an investment decision. Targacept, Inc. We are a biopharmaceutical company engaged in the design, discovery and development of a new class of drugs to treat multiple diseases and disorders of the central nervous system by selectively targeting neuronal nicotinic acetylcholine receptors, or NNRs. NNRs are found on nerve cells throughout the nervous system and serve as key regulators of nervous system activity. Our product candidates are designed to selectively target specific NNR subtypes to promote positive medical effects and limit or potentially eliminate adverse side effects. We are developing our most advanced product candidates as treatments for target indications in three therapeutic areas: cognitive impairment, pain and depression. Within these areas, we have three product candidates in clinical development and three preclinical product candidates. We have worldwide commercialization rights for all of our product candidates. Our most advanced product candidates are: Cognitive Impairment • Ispronicline (TC-1734). Ispronicline is a novel small molecule that we are developing as an oral treatment for conditions marked by cognitive impairment that afflict the elderly, including Alzheimer’s disease and age associated memory impairment, commonly referred to as AAMI. In 2004, we completed two Phase II clinical trials of ispronicline, one in AAMI and one in mild cognitive impairment, commonly referred to as MCI. We are currently conducting a separate Phase II clinical trial of ispronicline in AAMI. We have two Phase II clinical trials of ispronicline in Alzheimer’s disease planned. We expect the first of these trials, which we plan to initiate in mid-2005, to assess ispronicline as a stand-alone treatment for mild Alzheimer’s disease. We expect the second of these trials, which we plan to initiate in the first quarter of 2006, to assess ispronicline as a complementary, or add-on, therapy to a currently approved treatment for mild to moderate Alzheimer’s disease. • TC-1827. TC-1827 is a novel small molecule that we are developing as an oral treatment for cognitive impairment associated with schizophrenia. TC-1827 is currently a preclinical product candidate. We plan to file an investigational new drug application, or IND, and initiate a Phase I clinical trial of TC-1827 in the first half of 2005. Pain • TC-2696. TC-2696 is a novel small molecule that we are developing as an oral treatment for acute post-operative pain. Depending on clinical trial results, available resources and other considerations, we may pursue development of TC-2696 for other classes of pain as well. In 2004, we completed a Phase I clinical trial of TC-2696. We plan to initiate a Phase I multiple rising dose clinical trial to further assess the safety and tolerability profile of TC-2696 in the second quarter of 2005. 1 Table of Contents Depression • Inversine and TC-5214. Inversine, which we believe is the only FDA-approved product designed to target an NNR, is our only product approved by the FDA for marketing. Inversine is approved for the management of moderately severe to severe essential hypertension, a high blood pressure disorder with an unknown origin. However, we believe that Inversine is prescribed predominantly for the treatment of neuropsychiatric disorders, including Tourette’s syndrome, autism and bipolar disorder. We are currently conducting a Phase II clinical trial of Inversine as an add-on therapy in patients with major depressive disorder. TC-5214 is one of the molecular components of mecamylamine hydrochloride, the active ingredient in Inversine. TC-5214 is currently a preclinical product candidate. If our ongoing Phase II clinical trial of Inversine is successful, we may accelerate the development of TC-5214 as an add-on therapy for depression. • TC-2216. TC-2216 is a novel small molecule that we are developing as an oral treatment for depression and anxiety disorders. TC-2216 is currently a preclinical product candidate. In 2005, we plan to conduct the additional preclinical toxicology studies necessary to support an IND for clinical trials of TC-2216. We also have preclinical programs for target indications outside these therapeutic areas in which we believe NNRs can be exploited for medical benefit, including schizophrenia, smoking cessation and obesity. We trace our scientific lineage to a research program initiated by R.J. Reynolds Tobacco Company in 1982 to study the activity and effects of nicotine, a compound that interacts non-selectively with all nicotinic acetylcholine receptors. There is a significant amount of published clinical data relating to nicotine, including studies in which individuals with Alzheimer’s disease and other conditions marked by cognitive impairment showed therapeutic improvement when treated with a nicotine patch. We have used this clinical data, together with our deep understanding of the biological characteristics and functions of NNRs that we have built over more than 20 years, to validate NNRs as potential targets for drugs to act upon.