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                                                                  Exhibit 10.6



                        SECOND AMENDMENT TO LEASE BETWEEN

                      SCIENCE PARK DEVELOPMENT CORPORATION

                                       and

                        GENAISSANCE PHARMACEUTICALS, INC.






Date:  December __, 1999

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         This Second Amendment to Lease (this "SECOND AMENDMENT") is made and
entered into as of the ____ day of December, 1999 by and between SCIENCE PARK
DEVELOPMENT CORPORATION, a Connecticut corporation having a principal place of
business at 25 Science Park, New Haven, Connecticut 06511 (herein referred to as
"LANDLORD") and GENAISSANCE PHARMACEUTICALS, INC., a Delaware corporation having
a principal place of business at Five Science Park, New Haven, Connecticut 06511
(herein referred to as "TENANT").

         WHEREAS, Landlord and Tenant are parties to a certain Lease dated as of
September 15, 1998 (the "ORIGINAL LEASE") as amended by First Amendment to Lease
of even date herewith (the "FIRST AMENDMENT"); collectively the Original Lease
and the First Amendment shall hereinafter be referred to as (the "LEASE");

         WHEREAS, pursuant to the Lease, Tenant leases from Landlord certain
space in the building known as Building 5 North in Science Park, New Haven,
Connecticut;

         WHEREAS, at the time the Original Lease was executed, it was Landlord's
intention to demolish the building known as Building 5 South, Science Park;

         WHEREAS, it is now Landlord's intention to renovate Building 5 South;

         WHEREAS, subject only to either party's right to terminate this Second
Amendment for lack of Landlord funding, if certain conditions are satisfied,
which conditions are set forth below, Tenant shall lease from Landlord: (i) the
entire second floor of Building 5 South in Science Park, which floor consists of
approximately 18,859 rentable square feet as shown on the floor plan attached
hereto as EXHIBIT A-1 (herein referred to as the "SECOND FLOOR SPACE"); (ii) the
bridge, if it is built by Tenant, as shown on the floor plan attached hereto as
EXHIBIT A-1 (herein referred to as the "BRIDGE"); and (iii) a certain amount of
space on the third floor of Building 5 South to be determined as specified in
Section 2 hereof (the "THIRD FLOOR SPACE"; collectively, the Second Floor Space,
the Bridge and the Third Floor Space shall herein be referred to as the
"ADDITIONAL SPACE"), upon and subject to the terms, covenants and conditions
contained in the Lease as modified by this Second Amendment; and

         WHEREAS, Landlord and Tenant desire to amend the Lease in certain
respects;

         NOW, THEREFORE, for good and valuable consideration, the receipt and
sufficiency of which is acknowledged by each of the parties, Landlord and Tenant
hereby agree as follows (capitalized terms used herein which are not otherwise
defined herein shall have the meaning given to such terms in the Lease):

1. RENOVATION OF BUILDING 5 SOUTH. All references in the Lease to the
"demolition of Building 5 South" are hereby deleted and replaced with the phrase
"renovation of Building 5 South", and all references in the Lease to "demolish
Building 5 South" are hereby deleted and replaced with the phrase "renovate
Building 5 South".

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2. THIRD FLOOR SPACE. Prior to the Additional Space Lease Commencement Date (as
defined below), Landlord, at its expense, shall cause Svigals Associates to
establish the rentable area and location of the Third Floor Space on the third
floor of Building 5 South. Landlord and Tenant agree that the Third Floor Space
will include only the space required for Tenant's mechanical equipment and the
rentable area shall be determined by Svigals Associates. Notwithstanding the
foregoing, if the building design requires the Third Floor Space to be shared by
Tenant and any other tenants of Building 5 South, the area of the Third Floor
Space may be increased, but, for purposes of calculating Tenant's rental
obligations with respect thereto, shall be apportioned among the tenants
actually using the space and be deemed to include only the rentable area
required by Tenant for its mechanical equipment, as determined by Svigals
Associates.

3. PREPARATION OF ADDITIONAL SPACE. As soon as Landlord receives funding
sufficient to pay for the work described in this Section (the "PREP WORK"),
Landlord, at its expense, shall (i) obtain required demolition permits and
selectively demolish and remove tenant improvements from the Additional Space,
(ii) cause to be removed from the Additional Space all asbestos, which removal
shall be performed in compliance with all applicable Environmental Laws and
Title 19a ("Public Health and Well-Being") of the Connecticut General Statutes,
including but not limited to Sections 19c-332 through 332e, concerning asbestos,
and any regulations promulgated thereunder, (iii) cause to be removed from the
Additional Space all lead-based paint, which removal shall be performed in
compliance with applicable laws, such that as a result of the removal no
occupants of Building Five South shall be exposed to airborne lead at levels
over the action level, as defined in 29 CFR Section 1910.1025, and (iv)
otherwise prepare the Additional Space for delivery of same to Tenant in a
vacant, broom clean condition, free of all furnishings, equipment, litter and
debris. Landlord agrees to use its best efforts to deliver possession of the
Additional Space to Tenant in the condition specified in the immediately
preceding sentence no later than six (6) weeks following Landlord's receipt of
funding as aforesaid.

4. DEFINITION OF LANDLORD'S WORK. Subject to Landlord's receipt of the funding
for the Prep Work and the Interior Work (as hereinafter defined), and pursuant
to the provisions of Sections 2.4B, 2.4E - H and 2.6 of the Original Lease,
Landlord at its expense shall undertake all of the Work described on EXHIBIT B-1
and EXHIBIT B-2 hereof (collectively, the "LANDLORD'S WORK"). Landlord hereby
agrees to complete the Landlord's Work in a good and workmanlike fashion,
otherwise Tenant relies on no warranties or representations, express or implied,
of Landlord or any agent or other party associated with Landlord as to its
condition or repair, or as to taxes or any other matter relating to the
Additional Space, except as otherwise expressly provided in the Lease, as
modified by this Second Amendment. In addition Landlord's representation
regarding compliance with laws set forth in the second sentence of Section 8.1
of the Original Lease is hereby deemed repeated with regard to the Landlord's
Work, as is the limitation on Tenant's remedy set forth in the balance of said
Section 8.1.

5. INTERIOR WORK AND CONTINGENCY.

                  A. Subject to the provisions of Section 5E below, Landlord, at
                  its expense, shall use its best efforts to substantially
                  complete that portion of the Landlord's Work described on
                  EXHIBIT B-2 attached hereto (the "INTERIOR WORK") so it does


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                  not delay Tenant's completion of the Tenant's Work (as
                  hereinafter defined), but in any event, no later than five (5)
                  months following the Additional Space Lease Commencement Date.
                  In addition, Landlord represents that all electrical,
                  mechanical, plumbing and other building systems serving the
                  Additional Space will be in working order on the Additional
                  Space Rent Commencement Date (as hereinafter defined).

                  B. Landlord and Tenant shall each use its best efforts to
                  collectively cause Fusco Corporation and Svigals Associates to
                  coordinate the Interior Work with the Tenant's Work (as
                  defined in Article 21 of this Second Amendment) with respect
                  to the Additional Space in order not to delay completion of
                  the Tenant's Work with respect to the Additional Space.

                  C. Landlord shall give Tenant prompt written notice following
                  Landlord's receipt of funding from CHFA for the Prep Work and
                  the Interior Work. If at any time after December 31, 1999,
                  Landlord has not received funding from CHFA for performance of
                  the Prep Work or the Interior Work, Tenant may elect to
                  initially fund the cost of the Prep Work and/or the Interior
                  Work with reimbursement from Landlord as hereinafter provided.

                           (i)      At any time after December 31, 1999 and
                                    prior to Landlord's receipt of funding from
                                    CHFA, Tenant may elect to fund the Prep Work
                                    and Interior Work by giving Landlord written
                                    notice. Within ten (10) business days
                                    following Landlord's receipt of such notice,
                                    Landlord shall release its contractor to
                                    proceed with the Prep Work and Interior
                                    Work, including, without limitation,
                                    obtaining all necessary building permits for
                                    both the Prep Work and the Interior Work.
                                    Landlord shall remain responsible for
                                    completion of the Prep Work and the Interior
                                    Work and shall reimburse Tenant for interest
                                    on all sums advanced by Tenant at seven and
                                    one-half percent (7 1/2%) per annum from the
                                    date of advance until the date of
                                    reimbursement.

                           (ii)     Landlord shall cause Landlord's construction
                                    manager to price the Prep Work and the
                                    Interior Work separately from each other and
                                    from the balance of the Landlord Work, and
                                    to deliver a schedule to Landlord and Tenant
                                    for completion of the Prep Work and the
                                    Interior Work. Landlord shall cause the
                                    parties' architect (Svigals Associates) to
                                    clearly delineate Prep Work, to the extent
                                    required, and all of the Interior Work on
                                    all plans and drawings.

                           (iii)    If Tenant elects to fund the Prep Work and
                                    the Interior Work in accordance with the
                                    provisions of Section 5C(i) above, and if
                                    Landlord receives CHFA funding prior to
                                    Tenant's funding of the Prep Work and the
                                    Interior Work, then Landlord shall use CHFA


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                                    funds to fund the cost of the Prep Work and
                                    the Interior Work. If CHFA funds the Prep
                                    Work and the Interior Work subsequent to
                                    Tenant's funding same, but before the
                                    Additional Space Rent Commencement Date,
                                    Tenant shall be reimbursed from the first
                                    disbursement of proceeds from CHFA at the
                                    time of such disbursement for the monies
                                    plus interest as aforesaid provided by
                                    Tenant to fund the Prep Work and the
                                    Interior Work. If Landlord receives funding
                                    from CHFA for the Prep Work and/or the
                                    Interior Work after the Rent Commencement
                                    Date, Tenant shall receive a credit against
                                    the Base Rent due hereunder and under the
                                    Lease equal to the funds advanced by Tenant
                                    for completing the Prep Work and the
                                    Interior Work, plus interest as aforesaid
                                    until Landlord receives the CHFA funding and
                                    repays Tenant.

                  D. Subject to the provisions of subsection 5E below, if
                  Landlord has not received funding for the Prep Work and the
                  Interior Work on or before March 31, 2000 (TIME IS OF THE
                  ESSENCE with respect to said date), either party hereto may
                  terminate this Second Amendment by giving written notice to
                  the other no later than 11:59 p.m. on April 15, 2000 (TIME IS
                  OF THE ESSENCE with respect to such date). Upon delivery of
                  such notice, in accordance with the provisions of Article 22
                  of the Lease, this Second Amendment shall be deemed null and
                  void and of no further force or effect.

                  E. If Landlord delivers the Landlord's Notice (as hereinafter
                  defined) to Tenant, the contingency set forth in subsection 5D
                  above shall be deemed null and void and Landlord shall be
                  deemed to have received monies sufficient to fund the entire
                  cost of the Prep Work and the Interior Work.

6. LANDLORD'S NOTICE. Promptly after the conditions of Subsections 3(i) -(iv)
have been satisfied, Landlord will deliver written notice thereof to Tenant
("LANDLORD'S NOTICE").

7. ADDITIONAL SPACE LEASE COMMENCEMENT DATE. Landlord hereby agrees to lease to
Tenant and Tenant hereby agrees to lease from Landlord the Additional Space,
upon and subject to the terms of the Lease, as modified by this Second
Amendment. Landlord shall deliver, and Tenant shall accept, exclusive possession
of the Additional Space on the date Tenant receives Landlord's Notice, which
date shall be deemed to be the Lease Commencement Date with respect to the
Additional Space (the "ADDITIONAL SPACE LEASE COMMENCEMENT DATE"). Landlord's
delivery of exclusive possession shall be subject to entries by the Landlord and
its contractors only as necessary to complete the Landlord's Work prior to the
date Tenant first occupies the Additional Space for its business purposes (the
"OCCUPANCY DATE"). Notwithstanding the foregoing, in accordance with the
provisions of Section 2 hereof, Tenant's use of the Third Floor Space may be in
common with Landlord and other tenants of Building 5 South. Landlord will only
permit the Third Floor Space to be used for mechanical space and not for office
space. Because Tenant will not have exclusive possession of the Additional Space
until the Occupancy Date, the parties


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hereby agree that the provisions of Sections 5.1, 7.2, 7.4, 7.5, 12.1E and 23.1
of the Original Lease shall not apply to Tenant with regard to the Additional
Space until the Occupancy Date.

8. ADDITIONAL SPACE. Commencing on the Additional Space Lease Commencement Date,
the Leased Premises shall be deemed to include the Additional Space for all
purposes under the Lease, and the terms, covenants and conditions of the Lease,
as modified by this Second Amendment, shall govern the rights, obligations and
liabilities of Landlord and Tenant with respect to the Additional Space. The
Leased Premises, as described in Section 1.1(a) of the Original Lease and as
shown on Exhibits A-1 and A-2 of the Original Lease, are sometimes referred to
in this Second Amendment as the "ORIGINAL LEASED PREMISES".

9. CONFIRMATION OF TERMS. The Expiration Date of the initial 5-year Term of the
Lease, as hereby amended, with respect to the entire Leased Premises, including
without limitation, the Additional Space, is February 28, 2004. The two 5-year
Extension Options granted in Section 2.2 of the Original Lease shall apply to
the entire Leased Premises, including without limitation, the Additional Space.
Tenant may not exercise an Extension Option with respect to less than the entire
Leased Premises.

10. ADDITIONAL SPACE RENT COMMENCEMENT DATE. Subject to extensions pursuant to
Sections 2.3B. and 2.3C. of the Original Lease, the Rent Commencement Date with
respect to the Additional Space (the "ADDITIONAL SPACE RENT COMMENCEMENT DATE")
shall mean the earlier of: (i) the date of the issuance of a temporary or
permanent certificate of occupancy for the entire Additional Space, or (ii) five
(5) months after the date of Tenant's receipt of Landlord's Notice. In
interpreting the provisions of Sections 2.3B and 2.3C of the Lease to this
Second Amendment, the term, "Interior Work" as used therein shall mean,
"Interior Work" as defined herein, and the term, "Rent Commencement Date" as
used therein shall mean, "Additional Space Rent Commencement Date" as defined
herein. At the request of either Landlord or Tenant, Landlord and Tenant shall
execute and deliver to each other a writing confirming the Additional Space
Lease Commencement Date and the Additional Space Rent Commencement Date.

11. RENT.

                  (a) Because Tenant will bear the cost of building the Bridge
                  if it is built, Tenant shall pay Additional Rent, but shall
                  have no obligation to pay Base Rent for the Bridge during the
                  Term or any Extension Term. In accordance with the provisions
                  of this Second Amendment, commencing on the Additional Space
                  Rent Commencement Date and continuing thereafter until the
                  Expiration Date of the Lease, Tenant shall pay to Landlord
                  Base Rent for the Additional Space (excluding the rentable
                  area of the Bridge and including only the rentable area of the
                  Second Floor Space (18,859 rentable square feet) and the
                  rentable area of the Third Floor Space (determined in
                  accordance with the provisions of Section 2 hereof)) at the
                  same rate per rentable square foot as Tenant is required to
                  pay from time to time with respect to the Original Leased
                  Premises, under Section 3.1 of the Original Lease. The parties
                  hereto hereby stipulate to the aforementioned rentable area of
                  the Second Floor Space.


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                  (b) Notwithstanding anything to the contrary contained herein,
                  for purposes of calculating each and every instance where
                  Additional Rent is payable hereunder with regard to the
                  Additional Space, the Additional Space shall be deemed to
                  include 100% of the rentable area of the Second Floor Space,
                  100% of the rentable area of the Bridge if it is built, as
                  determined in accordance with the provisions of Section 22
                  hereof, and the rentable area of the Third Floor Space, as
                  determined in accordance with the provisions of Section 2
                  hereof. Commencing on the Additional Space Rent Commencement
                  Date and continuing thereafter until the Expiration Date of
                  the Lease, Tenant shall: (i) pay for electricity and gas
                  consumed on the Additional Space in accordance with Section
                  3.4 of the Original Lease, (ii) pay Additional Rent with
                  respect to the Additional Space in accordance with Section 3.5
                  of the Original Lease, and (iii) a portion of the Taxes in
                  accordance with Article 4 of the Lease, as hereby amended.

                  (c) In addition, subject to the provisions of Section 7(b)
                  hereof, Tenant shall pay with respect to the Additional Space
                  Tenant's OE Share (as hereinafter defined) of increases in
                  Operating Expenses over the Base Expense Year (as hereinafter
                  defined) in accordance with the terms of Article 37 of the
                  Lease, as amended by this Second Amendment.


12. DEFINITIONS. The second sentence of Section 4.1(d) of the Original Lease as
modified by the First Amendment is hereby deleted and substituted therefor is
the following:

                           "Tenant's Pro-Rata Share" shall mean a fraction, the
                           numerator of which shall be the total number of
                           rentable square feet in the Leased Premises (taking
                           into account that the rentable area of the Additional
                           Space shall be calculated in accordance with the
                           provisions of Section 11(b) hereof), as same may
                           increase or decrease from time to time, and the
                           denominator of which shall be the total number of
                           rentable square feet in Building 5 North and Building
                           5 South combined, as same may increase or decrease
                           from time to time, plus the rentable area of the
                           Bridge, if it is built; Landlord represents that as
                           of the date hereof the combined area of Building 5
                           North and Building 5 South, excluding the Bridge,
                           measured in rentable square feet is 102,938 rentable
                           square feet.

13. TAX PAYMENT; ENTERPRISE ZONE. (a) Commencing on the Additional Space Rent
Commencement Date, subparagraph 9(a)(ii) of the First Amendment (which modifies
Section 4.2 of the Original Lease) is hereby deleted and substituted therefor is
the following:

                  "Commencing on the Additional Space Rent Commencement Date,
                  Tenant shall pay to Landlord as Additional Rent due hereunder,
                  for any Tax Year, any part of which occurs after the
                  Additional Space Rent


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                  Commencement Date and during the Term or any Extension Term,
                  an amount (also the "TAX PAYMENT") equal to: (i) Tenant's
                  Pro-Rata Share (as defined in the Second Amendment) of the
                  Taxes attributable to the Base Building, plus (ii) 100% of the
                  Taxes attributable to all of the Tenant's Work (which for
                  purposes of the balance of this Article 4, unless specified to
                  the contrary, shall mean collectively Tenant's Work as defined
                  under the Original Lease, the First Amendment and the Second
                  Amendment)."

14. TAX RELIEF. Section 4.4 of the Original Lease as amended by the First
Amendment is hereby deleted and substituted therefor is the following: "Tenant
shall be entitled to Tenant's Pro-Rata Share of any real estate tax relief or
other forms of assistance or relief that may be negotiated by Landlord with the
City of New Haven in connection with the refurbishment of Building 5 North and
Building 5 South and the underlying land that is part of the tax parcel
containing Building 5 North and Building 5 South."

15. PARKING. The rental of the Additional Space will include the use of fifty
(50) parking spaces in addition to the eighty (80) parking spaces provided for
under the Original Lease and the twenty-five (25) parking spaces provided for
under the First Amendment. The term "TENANT'S PARKING SPACES" shall be amended
to include such additional fifty (50) parking spaces, bringing the total of
Tenant's Parking Spaces to one hundred fifty-five (155). One-half of said
additional fifty (50) parking spaces shall be made available to Tenant on the
Occupancy Date and the other half shall be made available to Tenant on the date
that is six (6) months following the Occupancy Date. All of Tenant's Parking
Spaces shall be located within the areas shown on EXHIBIT A-3 attached hereto
and made a part hereof at all times during the Term or any Extension Term.

16. OPTION TO LEASE FURTHER SPACE. Effective as of the Additional Space Lease
Commencement Date, Section 1.3B. of the Original Lease shall be amended so that
as amended it shall read in its entirety as follows:

         B. BUILDING 5. Tenant will have the option to lease any available space
         in Building 5 North and any available space on the third floor of
         Building 5 South, provided that, in either case, such available space
         is either 2,000 square feet or larger or contiguous to the Leased
         Premises, in either case, as such space becomes available ("AVAILABLE
         SPACE") on the same terms and conditions as set forth in the Original
         Lease, except for Base Rent, Additional Rent and parking, for the
         balance of the Term, or any extension thereof. Base Rent for the
         Available Space shall be at fair market value as determined by the
         Landlord. Additional Rent in addition to Base Rent, attributable to the
         Available Space shall constitute: (i) Tenant's OE Share of increases in
         Operating Expenses pursuant to the terms of Article 37 of the Lease as
         modified below by this Second Amendment; (ii) the cost of electricity
         and gas consumed on the Available Space in the manner set forth in the
         Utilities Rider attached to the Original Lease as EXHIBIT C; and (iii)
         Tenant's Pro-Rata Share of Taxes and Enterprise Zone benefits shall be
         increased to include the rentable area of the Available Space in the
         numerator with regard to the Base Building and Tenant shall be
         responsible for 100% of the Taxes, and entitled to 100% of the


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         Enterprise Zone benefits, attributable to its tenant improvements to
         the Available Space. The same amount of parking spaces that Landlord is
         offering to another tenant shall be offered to Tenant with the
         Available Space. Landlord will notify Tenant in writing of the
         availability of each piece of Available Space and the proposed fair
         market value rent and number of accompanying parking spaces promptly
         after becoming aware that such Available Space will be available for
         lease. In order to exercise its option to lease the Available Space,
         Tenant must notify Landlord of its acceptance in writing within ten
         (10) business days after Tenant's receipt of written notice from
         Landlord of the availability thereof. If Tenant fails to exercise its
         option within said ten (10) business day period, Landlord shall be free
         to lease the Available Space in question for a term or terms and for a
         rental or rentals and upon such other terms as Landlord in its sole
         discretion determines. Notwithstanding the foregoing, before leasing
         the Available Space in question to a third party for a total effective
         rent that is eighty-five (85%) percent of, or less than eighty-five
         (85%) percent of the total effective rent at which Landlord offered the
         space to Tenant, Landlord must re-offer such Available Space to Tenant
         by written notice at the same rent (and number of parking spaces) that
         Landlord is prepared to accept from a third party. Tenant shall have
         five (5) business days from receipt of Landlord's re-offer to accept
         the said Available Space at the said effective rent or Landlord shall
         be free to lease the said Available Space to a third party. For
         purposes of this Section 1.3B, space shall not be deemed "Available
         Space" unless the existing tenant for the space has declined to extend
         its tenancy.


17. OPERATING EXPENSES. Tenant's obligation to pay Operating Expenses for the
Additional Space and any Available Space shall be governed by the provisions of
Article 37 of the Lease except that:

         (a) With respect to the Additional Space, "BASE EXPENSE YEAR" shall
         mean the twelve (12) month period commencing on the date Tenant first
         occupies the Additional Space for purposes of conducting its business
         thereon. With respect to the Available Space, "BASE EXPENSE YEAR" shall
         mean the twelve (12) month period commencing on the date Tenant first
         occupies the Available Space for purposes of conducting its business
         thereon. In any event, if the Building is not fully occupied during all
         or a portion of either the Base Expense Year with respect to the
         Additional Space or the Base Expense Year with respect to any Available
         Space, Landlord shall, in accordance with sound accounting and
         management practices, determine the amount of Operating Expenses that
         would have been included in such Base Expense Year if the Building had
         been fully occupied and the amount so determined shall be deemed to be
         the Operating Expenses incurred in the corresponding Base Expense Year.

         (b) With respect to the Additional Space, "TENANT'S OE SHARE" shall
         mean a fraction, the numerator of which shall be the total of the
         rentable area of the Additional Space calculated in accordance with the
         provisions of Section 11(b) hereof, and the


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         denominator of which shall be the total number of rentable square feet
         in the Building 5 North and Building 5 South, plus the rentable area of
         the Bridge, if it is built. With respect to the Available Space,
         "TENANT'S OE SHARE" shall mean a fraction, the numerator of which shall
         be the rentable area of the Available Space, and the denominator of
         which shall be the total number of rentable square feet in the Building
         5 North and Building 5 South, plus the rentable area of the Bridge, if
         it is built.

         (c) Tenant's obligation to begin paying Operating Expenses with respect
         to the Additional Space shall not commence until the first Operating
         Expense Year occurring immediately following the Base Expense Year
         attributable to the Additional Space (as defined in this Second
         Amendment), and Tenant's obligation to begin paying Operating Expenses
         with respect to the Available Space in question shall not commence
         until the first Operating Expense Year occurring immediately following
         the Base Expense Year attributable to the Available Space.

         (d) On or before the first day of each Operating Expense Year following
         the Base Expense Year (as defined in this Second Amendment) Landlord
         shall give Tenant statements of the estimated amount of increase in
         Operating Expenses that Tenant will owe with respect to the Additional
         Space (and any Available Space if Tenant exercises its option pursuant
         to Section 11 hereof) for the ensuing Operating Expense Year, and
         Tenant shall make payments monthly in accordance with such statement.

18. AS-IS CONDITION. Subject to completion of the Landlord's obligations set
forth in this Second Amendment, including without limitation, completion of the
Landlord's Work, Landlord shall tender Tenant possession of the Additional Space
in its then "as is" condition and Tenant agrees to accept possession of the
Additional Space in its then "as is" condition, broom clean.

19. EXTERIOR WORK-BUILDING 5 SOUTH. Landlord hereby agrees to use commercially
reasonable efforts to complete the EXTERIOR WORK (as defined in Section 5 of
EXHIBIT B-1) prior to the Occupancy Date. If Landlord has performed and
completed work to the exterior of Building 5 South, but, in Tenant's opinion,
the exterior of Building 5 South does not have a look comparable in quality to
Building 4 after December 31, 2000, then Tenant shall have the same rights and
remedies as it has under Section 2.4E. and Section 2.4G. of the Original Lease
with respect to work performed to the exterior of Building 5 North. If Landlord
has performed no work to the exterior of Building 5 South by December 31, 2000,
then, notwithstanding anything to the contrary contained in the Second
Amendment, Tenant's sole and exclusive remedy for such breach by Landlord of its
obligation to perform Exterior Work shall be the same as the remedy available to
Tenant under Section 2.4G of the Lease, subject to Section 4.2H, with respect to
a breach by Landlord of its obligation to perform Exterior Work to Building 5
North. In interpreting the provisions of Sections 2.4E., 2.4G. and 2.4H. of the
Original Lease to this Second Amendment: (i) the term "Building Five North"
shall be deemed to mean "Building Five South"; (ii) the term "Exterior Work"
shall be deemed to mean "Exterior Work" as herein defined; (iii) the term
"Completion Date" shall be deemed to mean the December 31, 2000; and


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(iv) the date for "Tenant's Notice" shall be deemed to be thirty (30) days
following December 31, 2000

20. LANDLORD'S WORK.

                  A. Landlord shall use its best efforts to complete the balance
                  of Landlord's Work described in EXHIBIT B-1 attached hereto by
                  December 31, 2000. Notwithstanding anything to the contrary
                  contained in this Second Amendment, in the event that all of
                  Landlord's Work described in EXHIBIT B-1 attached hereto
                  (other than the Exterior Work) is not substantially complete
                  by December 31, 2000, Tenant shall be entitled, as its sole
                  and exclusive remedy, to a pro rata reduction in Base Rent
                  with respect to the Additional Space for any period after
                  December 31, 2000 that such Landlord's Work (other than the
                  Exterior Work) is not substantially complete, such rent
                  reduction to be determined by a mutually-agreed upon
                  commercial real estate broker with ten (10) years of
                  experience in New Haven. If such Landlord's Work is
                  substantially completed after December 31, 2000, Base Rent
                  with respect to the Additional Space payable hereunder shall
                  be reinstated to the level set forth in Section 11(a) hereof
                  effective as of the date of substantial completion of such
                  Landlord's Work is achieved.

                  B. Substantial completion of the Landlord's Work shall be
                  evidenced by issuance of a certificate of occupancy.

21. TENANT'S WORK. Tenant, at Tenant's expense, agrees to make improvements to
the Additional Space pursuant to plans and specifications approved by Landlord.
Such improvements shall be deemed "TENANT'S WORK" and such plans and
specifications shall be deemed "TENANT'S PLANS", and the terms of Section 2.7(a)
of the Original Lease shall govern the approval of same. It is currently
Tenant's intention that the Tenant's Work will include the construction of the
Bridge to connect the second floor of Building 5 North and the second floor of
Building 5 South at the East end of the buildings. Tenant shall not be penalized
in any manner if Tenant does not build the Bridge as part of the Tenant's Work.
Subject to satisfaction of the funding contingency for the Prep Work and the
Interior Work set forth in Section 5 hereof, Tenant shall proceed with
reasonable due diligence to perform Tenant's Work following funding of Tenant's
new loan from Connecticut Innovations, Inc. (the "NEW CII LOAN") and the
issuance of a building permit therefor.

22. THE BRIDGE. If Tenant builds the Bridge, then for all purposes under the
Lease, the Bridge shall be deemed a part of the Leased Premises, except that
Tenant shall not be required to pay Base Rent with respect to the Bridge. The
rentable area of the Bridge shall be remeasured by Svigals Associates at
Tenant's expense promptly after construction and included as part of the Leased
Premises for purposes of calculating Tenant's Pro-Rata Share and for purposes of
calculating Tenant's OE Share (as both terms are defined in this Second
Amendment). The parties agree that the usable area and the rentable area of the
Bridge will be the same. Similarly, if the Bridge is not constructed, the
rentable area of the Leased Premises for purposes of calculating Additional Rent
shall not include the rentable area of the Bridge. Tenant shall have


                                       10
<PAGE>


no obligation to remove or restore the Bridge upon surrender of the Leased
Premises to Landlord, notwithstanding the provisions of Section 6.2 of the
Original Lease.

23. LOBBY AND BATHROOMS. For all purposes under the Lease, the lobby and
bathrooms between the Original Leased Premises and the Additional Space shall be
deemed a part of the Additional Space and are included in the calculation of
Base Rent Tenant is obligated to pay hereunder. In addition, the rentable square
footage of the said lobby and bathrooms is included in the calculation of
Tenant's Pro-Rata Share of Taxes under Article 4 of the Lease, as amended by
this Second Amendment, and for purposes of calculating Tenant's OE Share as
defined in Section 12 hereof.

24. EXHAUST CHASES-ADDITIONAL SPACE. During preparation of the Tenant's Plans,
Landlord and Tenant shall agree upon the location of four (4) ventilation
exhaust chases, which shall be shown on Tenant's Plans. Landlord reserves the
right, at Landlord's sole expense, to build said ventilation exhaust chases in
the future, and shall undertake such building at a mutually agreeable time.

25. THIRD FLOOR BUILDING 5 SOUTH. In the event Landlord in its sole discretion
elects to construct a third floor in Building 5 South, then in such event
Landlord shall complete the base building construction associated with the
addition of a third floor and any known floor penetrations prior to the
Occupancy Date. Construction of tenant work on the third floor of Building 5
South will be subject to the provisions regarding Landlord's Work set forth in
Section 2.6 of the Original Lease as modified by this Second Amendment. If
during the performance of tenant work on the 3rd floor of Building 5 South,
Tenant is denied reasonable access to its space or Tenant is unable to conduct
it's business in the Additional Space, in either case due to the activities of
Landlord's or another tenant's contractors performing such construction, for a
period of three (3) consecutive business days, then, in such event, Tenant shall
receive, as Tenant's sole remedy, an abatement in Base Rent for the Additional
Space of one day for each day beyond said three (3)-day period that Tenant
continues to be denied reasonable access to its space or is unable to conduct
its business in the Additional Space.

26. SUBORDINATION AND NON-DISTURBANCE. As used herein, the term "LANDLORD'S
LENDER" shall mean and refer to the Connecticut Housing Finance Authority
("CHFA"), the Connecticut Development Authority ("CDA") and each future lender
who may from time to time extend credit to Landlord which extensions of credit
may be secured in whole or in part by a mortgage, deed of trust, ground lease or
other security interest affecting the real property of which the Additional
Space is a part. Tenant's obligations under the First Amendment and under this
Second Amendment are subject to receipt of non-disturbance agreements: (A) from
CDA, simultaneously with the execution and delivery of this Second Amendment,
and (B) from CHFA, both of which shall be substantially similar in form and
content to the form of Non-Disturbance, Subordination and Attornment Agreement
attached as EXHIBIT H and made a part of the Original Lease. Provided CHFA and
CDA execute and deliver said non-disturbance agreements, the Lease, as modified
by this Second Amendment, shall be subject and subordinated to: (a) all security
interests in favor of CHFA and CDA affecting the Leased Premises, including
without limitation the Additional Space, or the property of which the Leased
Premises are a part, and (b)


                                       11
<PAGE>


all present and future mortgages, deeds of trust and other security interests,
including leasehold mortgages, granted by Landlord in favor of CHFA and CDA and
affecting the Leased Premises, including without limitation the Additional
Space, or the property of which the Leased Premises are a part. Tenant agrees to
execute, at no expense to Landlord, any instrument which may reasonably be
deemed necessary or desirable by Landlord, CHFA or CDA or to further effect the
subordination of the Lease, as modified by this Second Amendment to Lease, to
any such security interest, provided however, Tenant's non-disturbance rights
are not affected. The Tenant's failure to strictly comply with this section will
constitute an Event of Default under this Lease.



                                       12
<PAGE>


27. NEW CII LOAN

                  A. Section 15.1B of the Original Lease is hereby modified to
                  permit Tenant to assign its right, title and interest in and
                  to this Second Amendment without Landlord's consent to CII as
                  collateral security for the New CII Loan, or to any Tenant's
                  Lender as collateral security for a similar loan to Tenant.
                  Tenant's Lender, including, without limitation, CII shall be
                  entitled to assign its rights under this Second Amendment or
                  to sublet the Additional Space to any entity, subject to the
                  provisions set forth in subsections 15.1B(a)-(d) of the
                  Original Lease.

                  B. Upon at least five (5) business days notice, Landlord, at
                  its expense, hereby agrees to enter into a new Consent and
                  Intercreditor Agreement substantially similar in form and
                  substance to the Intercreditor Agreement (as defined in
                  Section 15.5(d) of the Original Lease) but relating to the New
                  CII Loan and the First Amendment and this Second Amendment.

                  C. Upon the closing of the New CII Loan, Landlord agrees to
                  execute and deliver an affidavit (a) verifying the
                  nonexistence of any tenants' rights in the Additional Space,
                  (b) verifying the nonexistence of any security interests in
                  personal property and fixtures that form a part of the
                  Additional Space, other than the rights therein, if any, of
                  the CDA and CHFA as the current Landlord's Lenders, and United
                  States Department of Commerce, Economic Development
                  Administration and (c) that Landlord has no notice of any
                  facts or circumstances not of record which could give rise to
                  the claim of any third party to rights of adverse possession
                  or use over the Additional Space or any part thereof in
                  derogation of Landlord's title. Upon the execution of this
                  Second Amendment, Landlord further agrees to obtain and
                  deliver a subordination of mechanic's liens, subordinated as
                  to the lien in favor of CII, executed by any contractor(s) who
                  have furnished any labor, services or materials in connection
                  with construction or repair work to the Building on behalf of
                  Landlord and would have a right to file a mechanic's lien that
                  would have priority over the mortgage filed in connection with
                  the New CII Loan.

28. AMENDED NOTICE OF LEASE. Article 30 of the Original Lease is hereby amended
to provide that at the request of either party, the notice of lease relating to
the Original Lease shall be amended to reflect the addition of the Additional
Space.

29. HVAC SERVICE. The reference to "Building 5 North" in Section 36A of the
Original Lease, as amended by the First Amendment, is hereby deleted and
substituted therefor is a reference to "Building 5 North and Building 5 South".
Landlord hereby acknowledges that the Additional Space will contain some
laboratories and that the requirement set forth in Section 36B of the Lease for
24-hour operation of Tenant's HVAC System 365 days a year applies to said
laboratories as well.


                                       13
<PAGE>


30. EFFECT. The Lease, as modified by this Second Amendment, remains in full
force and effect.

31. MERGER. All understandings, letters of intent or agreements between Tenant
and Landlord, which predate this Second Amendment are merged herein. No oral
statements or representations or prior written communications by or between the
parties dealing with the subject matter of this Second Amendment shall be
binding or effective. This Second Amendment and the Lease are the sole and
complete expression of the agreement between Landlord and Tenant as to the
subject matter thereof.

32. SEVERABILITY. If any of the provisions of this Second Amendment, or its
application, is held by any court or in arbitration to be invalid or
inapplicable, such decision shall not affect any other term, provision, covenant
or condition of this Second Amendment. Notwithstanding the foregoing, if the
invalid provision has the effect of reducing the rent to be paid by Tenant,
Landlord may cancel the Lease.

33. GOVERNING LAW. The laws of the State of Connecticut will govern the
interpretation of this Second Amendment.

34. BINDING NATURE. This Second Amendment shall be binding upon the parties
hereto and upon their heirs, administrators, executors, successors and assigns,
and shall not be construed against the party that drafted it. The paragraph
headings are for the parties' convenience and shall not be deemed to effect the
meaning of this Second Amendment or otherwise.

         IN WITNESS WHEREOF, the parties hereto have hereunto set their hands
and seals as of the day and year first above written.

SCIENCE PARK DEVELOPMENT CORPORATION



By:      /s/ Dennis C. Lyndon
         -----------------------
         Dennis C. Lyndon
         Director of Development
         Duly Authorized


GENAISSANCE PHARMACEUTICALS, INC.



By:      /s/ Kevin Rakin
         --------------------------
         Kevin Rakin
         Executive Vice President
         Duly Authorized



                                       14
<PAGE>


         Pursuant to Section 34.2 of the Lease dated September 15, 1998 by and
between Science Park Development Corporation and Genaissance Pharmaceuticals,
Inc., the undersigned hereby consent to the foregoing First Amendment to Lease.

CONNECTICUT DEVELOPMENT AUTHORITY


By:      /s/ Richard R. Barredo             Date: 12/14/99
         ----------------------
         Print Name: Richard R. Barredo
         Print Title: Senior Vice President


THE CONNECTICUT HOUSING FINANCE AUTHORITY


By:      /s/ Gary E. King                   Date: 12/16/99
         ----------------------
         Print Name: Gary E. King
         Print Title: President and
                      Executive Director


CONNECTICUT INNOVATIONS, INC.


By:      /s/ Victor Budnick                 Date: 12/14/99
         -----------------------
         Print Name: Victor Budnick
         Print Title: President and
                      Executive Director



                                       15
<PAGE>



                                   EXHIBIT A-1

                          FLOOR PLAN OF 2ND FLOOR SPACE
                                BUILDING 5 SOUTH


<PAGE>



                                   EXHIBIT A-2

                          FLOOR PLAN OF 3RD FLOOR SPACE
                                BUILDING 5 SOUTH


<PAGE>



                                   EXHIBIT A-3

                            DESIGNATED PARKING AREAS


<PAGE>


                                   EXHIBIT B-1

                       LANDLORD'S WORK - BUILDING 5 SOUTH

1.       Building 5 South's entryway, including its exterior door, will be
         renovated to include painting, new carpeting, acoustical ceilings.

2.       All non-double pane windows will be replaced to match the new windows
         at Building 5 North.

3.       The fire alarm system will be updated as required by code.

4.       The roof will be repaired or replaced as required.

5.       The exterior of Building 5 South will be cleaned and upgraded with the
         intent of achieving a look comparable in quality to Building 4 (that
         portion of Landlord's Work described in this subparagraph 5 is referred
         to in this Second Amendment as the "EXTERIOR WORK").


<PAGE>



                                   EXHIBIT B-2

                        INTERIOR WORK - BUILDING 5 SOUTH


1.       Piping and supply of chilled and hot water sufficient to operate
         Tenant's HVAC System will be installed up to the Additional Space.

2.       Modifications and/or upgrades to fire alarm system and sprinkler system
         if required by fire marshal.

3.       Installation of hot water supply and return.

4.       Installation of baseboard heating system.

5.       Window replacement work.