<Page>



                       SECURITIES AND EXCHANGE COMMISSION
                             WASHINGTON, D.C. 20549

                                -----------------

                                   FORM 10-K/A
                                (AMENDMENT NO. 1)

                        FOR ANNUAL AND TRANSITION REPORTS
                     PURSUANT TO SECTIONS 13 OR 15(d) OF THE
                         SECURITIES EXCHANGE ACT OF 1934

(MARK ONE)

/X/      ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
         SECURITIES EXCHANGE ACT OF 1934

                  FOR THE FISCAL YEAR ENDED: DECEMBER 31, 2004
                                       OR

/ /      TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE
         SECURITIES EXCHANGE ACT OF 1934

         FOR THE TRANSITION PERIOD FROM ______________ TO ______________

                          COMMISSION FILE NO. 000-30981

                                -----------------

                        GENAISSANCE PHARMACEUTICALS, INC.
             (Exact name of registrant as specified in its charter)

<Table>
<S>                                                                 <C>
                       DELAWARE                                                    06-1338846
           (State or other jurisdiction of                            (I.R.S. Employer Identification No.)
            incorporation or organization)

                   FIVE SCIENCE PARK
                NEW HAVEN, CONNECTICUT                                                06511
       (Address of principal executive offices)                                    (Zip Code)
</Table>

       Registrant's telephone number, including area code: (203) 773-1450

                                -----------------

Securities registered pursuant to Section 12(b) of the Act:   NONE

<Table>
<S>                                                          <C>
Securities registered pursuant to Section 12(g) of the Act:   COMMON STOCK, $.001 PAR VALUE
                                                                  (Title of each class)
</Table>


Indicate by check mark whether the registrant (1) has filed all reports required
to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during
the preceding 12 months (or for such shorter period that the registrant was
required to file such reports), and (2) has been subject to such filing
requirements for the past 90 days. Yes /X/ No / /

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405
of Regulation S-K is not contained herein, and will not be contained, to the
best of registrant's knowledge, in definitive proxy or information statements
incorporated by reference in Part III of this Form 10-K or any amendment to the
Form 10-K. /X/

Indicate by check mark whether the registrant is an accelerated filer (as
defined in Exchange Act Rule 12b-2). Yes /X/ No / /

The aggregate market value of Common Stock held by non-affiliates of the
registrant (without admitting that any person whose shares are not included in
the calculation is an affiliate) was $120,064,182 based on the last reported
sale price of the Common Stock on The NASDAQ National Market on June 30, 2004.

Number of shares of the registrant's Common Stock outstanding as of March 9,
2005: 34,728,829.


<Page>


                                EXPLANATORY NOTE

The purpose of this Amendment No. 1 to the Registrant's Annual Report on Form
10-K for the year ended December 31, 2004, is to file Exhibits 10.64, 10.66,
10.67 and 10.68. This Amendment No. 1 does not reflect events occurring after
the filing of the original Form 10-K on March 15, 2005, or modify or update
those disclosures affected by subsequent events. No other modifications or
changes have been made to the Form 10-K as originally filed or the exhibits
filed therewith, except for changes to the certifications required by (i) Rules
13a-14(a)/15d-14(a) promulgated under the Securities Exchange Act of 1934, as
amended, and (ii) 18 U.S.C. Section 1350.


                                       2


<Page>


                                   SIGNATURES

         Pursuant to the requirements of Section 13 or 15(d) of the Securities
Exchange Act of 1934, as amended, the Registrant has duly caused this Amendment
No. 1 to its Annual Report on Form 10-K to be signed on its behalf by the
undersigned, thereunto duly authorized, in the Town of New Haven, Connecticut,
on April 26, 2005.

                                GENAISSANCE PHARMACEUTICALS, INC.



                                By: /s/ Kevin Rakin
                                    ------------------------------------------
                                    Kevin Rakin
                                    Chief Executive Officer


                                      II-1


<Page>


                                  EXHIBIT INDEX

<Table>
<Caption>
EXHIBIT NO.                                              DESCRIPTION OF DOCUMENT
----------                                               -----------------------
<S>                <C>
2.1^(1)             Asset Purchase Agreement between Genaissance and DNA Sciences, Inc., dated March 28, 2003.

2.2^(1)             Amendment No. 1, dated May 5, 2003, to Asset Purchase Agreement between Genaissance and DNA
                    Sciences, Inc., dated March 28, 2003.

2.3^(2)             Agreement and Plan of Merger, dated as of December 18, 2003, by and among Genaissance, Brown
                    Acquisition Corp. and Lark Technologies, Inc.

3.1(3)              Amended and Restated Certificate of Incorporation, as amended.

3.2(4)              Amended and Restated By-Laws.

4.1(4)              Specimen Certificate of Genaissance's Common Stock, $.001 par value.

4.2(4)              Form of Common Stock Purchase Warrant, together with a list of warrant holders.

4.3(5)              Warrant, dated as of October 29, 2003 issued by Genaissance to RAM Trading, Ltd.

4.4(5)              Specimen Certificate of Genaissance's Series A Preferred Stock, $.001 par value.

4.5++               Warrant to Purchase Common Stock, dated as of June 30, 2004, issued by Genaissance to Ritchie
                    Long/Short Trading Ltd.

4.6(6)              Form of Warrant, dated as of November 18, 2004, issued by Genaissance to the Investors named in
                    that certain Securities Purchase Agreement of even date therewith.

10.1*(4)            2000 Amended and Restated Equity Incentive Plan, as amended.

10.2*(4)            Stock Option Plan.

10.3*(4)            Employee Stock Purchase Plan 2000, as amended.

10.4(4)             Lease Agreement between Genaissance and Science Park Development Corporation dated September 15,
                    1998.

10.5(4)             Amendment No. 1 to Lease Agreement between Genaissance and Science Park Development Corporation
                    dated December 1, 1999.

10.6(4)             Amendment No. 2 to Lease Agreement between Genaissance and Science Park Development Corporation
                    dated December 16, 1999.

10.7*(4)            Genaissance 401(k) Plan.

10.8+(4)            Collaboration Agreement between Genaissance and Telik, Inc. dated February 11, 1998.

10.9(4)             First Amendment, dated February 11, 1999, to the Collaboration Agreement between Genaissance and
                    Telik, Inc. dated February 11, 1998.

10.10+(4)           License Agreement between Genaissance and Visible Genetics, Inc. dated November 21, 1996.

10.11+(4)           Patent License Amending Agreement between Genaissance and Visible Genetics, Inc. dated March 16,
                    2000.

10.12(4)            Loan Agreement between Genaissance and Connecticut Innovations, Incorporated dated September 15,
                    1998.
</Table>


                                      II-2


<Page>


<Table>
<S>                <C>
10.13(4)            Loan Agreement between Genaissance and Connecticut Innovations, Incorporated dated December 1,
                    1999.

10.14+(4)           Strategic Alliance Agreement between Genaissance and Sequenom, Inc. dated as of May 3, 2000.

10.15(4)            Letter Agreement with Connecticut Innovations, Incorporated dated June 2, 2000.

10.16(4)            Second Amended and Restated Registration Rights Agreement with the purchasers of Series A and
                    Series KBL Non-voting Preferred Stock dated March 10, 2000.

10.17(4)            Amended and Restated Registration Rights Agreement with the purchasers of Series B and Series
                    KBH Preferred Stock dated March 10, 2000.

10.18(4)            Amendment No. 3 to Lease Agreement between Genaissance and Science Park Development Corporation
                    dated June 1, 2000.

10.19(4)            Purchase Agreement with Connecticut Innovations, Incorporated dated March 10, 1994.

10.20(4)            Financing Agreement with Connecticut Innovations, Incorporated dated November 16, 1994.

10.21(4)            Financing Agreement with Connecticut Innovations, Incorporated dated September 10, 1996.

10.22(4)            Agreement Concerning Conversion of Convertible Note and Connecticut Presence with Connecticut
                    Innovations, Incorporated dated August 24, 1998.

10.23(4)            Supplemental Agreement to Agreement Concerning Conversion of Convertible Note and Connecticut
                    Presence with Connecticut Innovations, Incorporated dated November 23, 1999.

10.24(4)            Letter Agreement with Connecticut Innovations, Incorporated dated February 17, 2000.

10.25(7)            Third Loan Agreement with Connecticut Innovations, Incorporated dated July 26, 2000.

10.26+(8)           Agreement with Pfizer Inc. dated August 29, 2001.

10.27+(8)           Mednostics(TM)Collaboration and License Agreement with Biogen, Inc. dated as of January 31, 2002.

10.28+(8)           International Sales Representative Agreement with Intec Web and Genome Informatics Corporation
                    dated as of February 4, 2002.

10.29(8)            Fourth Amendment to Lease between Science Park Development Corporation and Genaissance dated
                    September 30, 2001.

10.30+(9)           Amendment, dated December 18, 2002, to Mednostics(TM)Collaboration and License Agreement with
                    Biogen, Inc. dated as of January 31, 2002.

10.31+(9)           Training and License Agreement with Becton, Dickinson and Company dated December 18, 2002.

10.32+(1)           Technology and Database License Agreement between Genaissance and Millennium Pharmaceuticals,
                    Inc., dated January 7, 2003.

10.33+(1)           Research Collaboration and License Agreement between Genaissance, Bayer AG and Bayer Healthcare
                    LLC, dated January 15, 2003.

10.34(1)            Amendment, dated February 6, 2003, to Agreement with Pfizer Inc., dated August 29, 2001.

10.35+(1)           Genotyping Services Agreement between Genaissance and Wayne State University, dated March 11,
                    2003.
</Table>


                                      II-3


<Page>


<Table>
<S>                <C>
10.36(1)            Amendment, dated March 12, 2003, to Master Equipment Lease Agreement between Genaissance and
                    General Electric Capital Corporation (successor-in-interest to Oxford Venture
                    Finance, LLC), dated June 10, 1999.

10.37*(1)           Management Incentive Program Summary.

10.38*(10)          Employment Agreement with Ben Kaplan, dated May 6, 2003.

10.39(5)            Series A Preferred Stock Purchase Agreement, dated as of October 29, 2003, by and between
                    Genaissance and RAM Trading, Ltd.

10.40(5)            Registration Rights Agreement, dated as of October 29, 2003, by and between Genaissance and RAM
                    Trading, Ltd.

10.41(11)           Loan and Security Agreement, dated as of September 30, 2003, by and between Genaissance and
                    Comerica Bank.

10.42+(12)          Consumer Genomics and HAP(TM)Technology License Agreement, dated as of November 17, 2003, by and
                    between Genaissance and Sciona Limited.

10.43+(12)          Investment Agreement between Genaissance, Prelude Trust PLC, Abbey National Treasury Services
                    Overseas Holdings and Sciona Limited, not dated.

10.44+(13)          Agreement, dated as of May 15, 2003, between Genaissance and Prometheus Laboratories, Inc.

10.45*(13)          Employment Agreement with Kevin Rakin dated as of  January 1, 2004.

10.46*(13)          Employment Agreement with Gerald F. Vovis dated as of  January 1, 2004.

10.47*(13)          Employment Agreement with Richard Judson dated as of  January 1, 2004

10.48*(13)          Employment Agreement with Ben D. Kaplan dated as of  January 1, 2004

10.49*(14)          Employment Agreement, dated as of December 18, 2003, by and between Genaissance and Carl
                    Balezentis.

10.50++             Letter Agreement, dated as of June 29, 2004, between Genaissance and RAM Trading, Ltd.

10.51+(15)          Strength Research License Agreement by and between Genaissance and AstraZeneca UK Limited dated
                    September 5, 2003.

10.52+(16)          License, Development and Cooperation Agreement by and between Merck KGaA and Genaissance dated
                    September 22, 2004.

10.53++             Waiver, dated October 5, 2004, to that certain Loan and Security Agreement by and between
                    Genaissance and Comerica Bank dated as of September 30, 2003.

10.54++             Waiver, dated November 8, 2004, to that certain Loan and Security Agreement by and between
                    Genaissance and Comerica Bank dated as of September 30, 2003.

10.55*(17)          Form of Nonstatutory Stock Option Agreement under Genaissance's 2000 Amended and Restated Equity
                    Incentive Plan, as amended.

10.56*(17)          Form of Incentive Stock Option Agreement under Genaissance's 2000 Amended and Restated Equity
                    Incentive Plan, as amended.

10.57(18)           Agreement and Acknowledgment by and between Genaissance and RAM Trading, Ltd., dated as of
                    November 15, 2004.
</Table>


                                      II-4

<Page>


<Table>
<S>                <C>
10.58(19)           Form of Securities Purchase Agreement, dated as of November 18, 2004, by and among Genaissance
                    and the Investors named therein.

10.59(20)           Termination Agreement by and between Genaissance and RAM Trading, Ltd., dated November 24,
                    2004.

10.60+,++           Amendment, dated as of July 16, 2004, to Agreement between Genaissance and Pfizer Inc., dated as
                    of August 29, 2001.

10.61*++            Summary of compensation arrangement applicable to Genaissance's Board of Directors.

10.62*++            Summary of compensation arrangement applicable to Genaissance's named executive officers.

10.63++             Waiver and Acknowledgement, dated as of November 18, 2004, by and between Genaissance and RAM
                    Trading, Ltd.

10.64               Letter Agreement, dated as of August 30, 2004, by and between Genaissance and RAM Trading, Ltd.
                    Filed herewith.

10.65++             First Amendment, dated March 16, 2004, to that certain Loan and Security Agreement by and
                    between Genaissance and Comerica Bank dated as of September 30, 2003.

10.66               Lease Agreement by and between Lark Technologies, Inc. and Westwood Venture Limited Partnership,
                    dated as of November 18, 1999.  Filed herewith.

10.67               Lease Agreement by and between Genaissance and Duke Realty Limited Partnership, dated as of
                    April 26, 2004.  Filed herewith.

10.68               Lease by Mr and Mrs D V Waterman to Lark Technologies Inc., dated as of July 14, 2004.  Filed
                    herewith.

14.1(13)            Code of Business Conduct and Ethics.

21.1++              Subsidiaries of Genaissance.

23.1++              Consent of PricewaterhouseCoopers LLP.

31.1                Certification pursuant to Rules 13a-14(a)/15d-14(a) promulgated under the Securities Exchange
                    Act of 1934, as amended.  Filed herewith.

31.2                Certification pursuant to Rules 13a-14(a)/15d-14(a) promulgated under the Securities Exchange
                    Act of 1934, as amended.  Filed herewith.

32.1                Certification pursuant to 18 U.S.C. 1350.  Filed herewith.

32.2                Certification pursuant to 18 U.S.C. 1350.  Filed herewith.
</Table>


------------------------
*        Indicates a management contract or compensatory plan.

+        Confidential treatment requested as to certain portions, which portions
         have been filed separately with the Commission.


                                      II-5


<Page>


^        The exhibits and schedules to these agreements have been omitted from
         this filing pursuant to Item 601(b)(2) of Regulation S-K. Genaissance
         will furnish copies of any of the exhibits and schedules to the SEC
         upon request.

++       Previously filed as Exhibits to the Registrant's Annual Report on Form
         10-K for the fiscal year ended December 31, 2004.

(1)      Filed as an exhibit to Genaissance's Quarterly Report on Form 10-Q, as
         amended (File No. 000-30981), for the quarter ended March 31, 2003 and
         incorporated herein by reference.

(2)      Filed as an exhibit to Genaissance's Current Report on Form 8-K (File
         No. 000-30981) filed with the SEC on December 22, 2003, as amended on
         February 17, 2004, and incorporated herein by reference.

(3)      Filed as an exhibit to Genaissance's Form 8-A/A (File No. 000-30981)
         filed with the SEC on December 16, 2004 and incorporated herein by
         reference.

(4)      Filed as an exhibit to Genaissance's Registration Statement on Form
         S-1, as amended (File No. 333-35314), and incorporated herein by
         reference.

(5)      Filed as an exhibit to Genaissance's Current Report on Form 8-K (File
         No. 000-30981) filed with the SEC on November 5, 2003 and incorporated
         herein by reference.

(6)      Filed as an exhibit to Genaissance's Current Report on Form 8-K (File
         No. 000-30981) filed with the SEC on November 22, 2004 and incorporated
         herein by reference.

(7)      Filed as an exhibit to Genaissance's Annual Report on Form 10-K (File
         No. 000-30981) for the year ended December 31, 2000 and incorporated
         herein by reference.

(8)      Filed as an exhibit to Genaissance's Annual Report on Form 10-K (File
         No. 000-30981) for the year ended December 31, 2001 and incorporated
         herein by reference.

(9)      Filed as an exhibit to Genaissance's Annual Report on Form 10-K, as
         amended (File No. 000-30981), for the year ended December 31, 2002 and
         incorporated herein by reference.

(10)     Filed as an exhibit to Genaissance's Quarterly Report on Form 10-Q, as
         amended (File No. 000-30981), for the quarter ended June 30, 2003 and
         incorporated herein by reference.

(11)     Filed as an exhibit to Genaissance's Quarterly Report on Form 10-Q, as
         amended (File No. 000-30981), for the quarter ended September 30, 2003
         and incorporated herein by reference.

(12)     Filed as an exhibit to Genaissance's Current Report on Form 8-K (File
         No. 000-30981) filed with the SEC on December 2, 2003, as amended on
         February 23, 2004, and incorporated herein by reference.

(13)     Filed as an exhibit to Genaissance's Annual Report on Form 10-K (File
         No. 000-30981) for the year ended December 31, 2003 and incorporated
         herein by reference.

(14)     Filed as an exhibit to Genaissance's Registration Statement on Form S-4
         (File No. 333-112737) filed with the SEC on February 12, 2004 and
         incorporated herein by reference.

(15)     Filed as an exhibit to Genaissance's Quarterly Report on Form 10-Q
         (File No. 000-30981) for the quarter ended June 30, 2004 and
         incorporated herein by reference.

(16)     Filed as an exhibit to Genaissance's Current Report on Form 8-K/A (File
         No. 000-30981) filed with the SEC on October 13, 2004 and incorporated
         herein by reference.


                                      II-6


<Page>


(17)     Filed as an exhibit to Genaissance's Quarterly Report on Form 10-Q
         (File No. 000-30981) for the quarter ended September 30, 2004 and
         incorporated herein by reference.

(18)     Filed as an exhibit to Genaissance's Current Report on Form 8-K (File
         No. 000-30981) filed with the SEC on November 16, 2004 and incorporated
         herein by reference.

(19)     Filed as an exhibit to Genaissance's Current Report on Form 8-K (File
         No. 000-30981) filed with the SEC on November 22, 2004 and incorporated
         herein by reference.

(20)     Filed as an exhibit to Genaissance's Current Report on Form 8-K (File
         No. 000-30981) filed with the SEC on November 29, 2004 and incorporated
         herein by reference.


                                      II-7