Document:

<PAGE>

                                                                    EXHIBIT 10.5

                        FIRST AMENDMENT TO LEASE BETWEEN

                      SCIENCE PARK DEVELOPMENT CORPORATION

                                       and

                        GENAISSANCE PHARMACEUTICALS, INC.

Date:    December 1, 1999

<PAGE>

         This First Amendment to Lease (this "FIRST AMENDMENT") is made and
entered into as of the 1st 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 "LEASE"), pursuant to which Tenant leases from Landlord
certain space in the building known as Building 5 North in Science Park, New
Haven, Connecticut;

         WHEREAS, Landlord desires to lease to Tenant and Tenant desires to
lease from Landlord certain space on the first floor of Building 5 North, which
space consists of approximately 7,953 rentable square feet as shown on the floor
plan attached hereto as EXHIBIT A-1 and certain mechanical space on the third
floor of Building 5 North, which space consists of approximately 156 rentable
square feet as shown on the floor plan attached hereto as EXHIBIT A-2 (herein
collectively referred to as the "FIRST AMENDMENT SPACE"), upon and subject to
the terms, covenants and conditions contained in the Lease as modified by this
First 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.       PREPARATION OF FIRST AMENDMENT SPACE. Landlord, at its expense, shall
         (i) obtain required demolition permits and selectively demolish and
         remove tenant improvements from the First Amendment Space, (ii) cause
         to be removed from the First Amendment 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 First
         Amendment 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 North 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 First Amendment 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 exclusive possession of the First
         Amendment Space to Tenant in the condition specified in the immediately
         preceding sentence by December 15, 1999.

<PAGE>

2.       LANDLORD'S NOTICE. Promptly after the conditions of Subsections 1(i)
         -(iv) have been satisfied, Landlord will deliver written notice thereof
         to Tenant ("LANDLORD'S NOTICE") .

3.       FIRST AMENDMENT SPACE LEASE COMMENCEMENT DATE. Landlord hereby agrees
         to lease to Tenant and Tenant hereby agrees to lease from Landlord the
         First Amendment Space, upon and subject to the terms of the Lease, as
         modified by this First Amendment. Landlord shall deliver, and Tenant
         shall accept, exclusive possession of the First Amendment Space on the
         date Tenant receives Landlord's Notice, which date shall be deemed to
         be the Lease Commencement Date with respect to the First Amendment
         Space (the "FIRST AMENDMENT SPACE LEASE COMMENCEMENT DATE").

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

5.       CONFIRMATION OF TERM & EXTENSIONS. Landlord and Tenant hereby agree
         that the Rent Commencement Date with respect to the Original Leased
         Premises was March 1, 1999 and the Expiration Date of the initial
         5-year Term of the Lease with respect to the entire Leased Premises,
         including the Original Leased Premises and the First Amendment Space,
         is February 28, 2004. The two 5-year Extension Options granted in
         Section 2.2 of the Lease shall apply to the entire Leased Premises,
         including the Original Leased Premises and the First Amendment Space.
         Tenant may not exercise an Extension Option with respect to less than
         the entire Leased Premises.

6.       FIRST AMENDMENT SPACE RENT COMMENCEMENT DATE. Subject to extensions
         pursuant to Sections 2.3B. and 2.3C. of the Lease, the Rent
         Commencement Date with respect to the First Amendment Space (the "FIRST
         AMENDMENT 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 First Amendment 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 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, "First Amendment 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 First Amendment Space Lease Commencement Date and the First
         Amendment Space Rent Commencement Date.

                                       2

<PAGE>

7.       RENT.

               (a) In accordance with the provisions of this First Amendment,
         Tenant shall pay to Landlord base rent for the First Amendment Space
         commencing on the First Amendment Space Rent Commencement Date and
         thereafter as follows:

<TABLE>
<CAPTION>
--------------------------------------------------------------------------------
       LEASE YEAR            BASE RENT/RSF       MONTHLY RENT       ANNUAL RENT
--------------------------------------------------------------------------------
  <S>                        <C>                 <C>                <C>
   1 3/1/99 - 2/28/00            $11.40             $ 7,704          $ 92,443
--------------------------------------------------------------------------------
   2 3/1/00 - 2/28/01            $12.20             $ 8,244          $ 98,930
--------------------------------------------------------------------------------
   3 3/1/01 - 2/28/02            $13.05             $ 8,819          $105,822
--------------------------------------------------------------------------------
  4-5 3/1/02 - 2/28/04           $16.05             $10,846          $130,149
--------------------------------------------------------------------------------
</TABLE>

                  (b) Commencing on the First Amendment Space Rent Commencement
         Date and continuing thereafter until the Expiration Date of the Lease,
         Tenant shall: (i) pay to Landlord Base Rent for the First Amendment
         Space 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,
         as more particularly set forth in Section 7(a) hereof; (ii) pay for
         electricity and gas consumed within the First Amendment Space in
         accordance with Section 3.4 of the Lease, (iii) pay Additional Rent
         with respect to the First Amendment Space in accordance with Section
         3.5 of the Lease, and (iv) a portion of the Taxes in accordance with
         Article 4 of the Lease, as hereby amended.

                  (c) In addition, commencing in the sixth Lease Year, with
         respect to First Amendment Space only, Tenant shall pay Tenant's OE
         Share (as hereinafter defined) of increases in Operating Expenses over
         the Base Expense Year in accordance with the terms of Article 37 of the
         Lease, as amended by this First Amendment.

8.       DEFINITIONS.

                  (a) The second sentence of Section 4.1(a) of the Lease is
         hereby deleted and substituted therefor is, "The Building shall mean
         Building 5 North and Building 5 South."

                  (b) The first sentence of Section 4.1(d) of the Lease is
         hereby deleted and substituted therefor is the following:

                                       3

<PAGE>

                           "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, 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; Landlord represents that as of the
                           date hereof the combined area of Building 5 North and
                           Building 5 South measured in rentable square feet is
                           102,938 rentable square feet.

                  (c) The Term " Property defined in Section 1.1(a) of the Lease
         is also known as Map 256, Block 0393 and Lot 00100 in the New Haven Tax
         Assessor's office.

9.       TAX PAYMENT; ENTERPRISE ZONE The text of Section 4.2 of the Lease is
         hereby deleted and substituted therefor is the following:

                  (a)      TAX PAYMENT.

                           (i) Commencing on the Rent Commencement Date up to
                  the day immediately preceding the First Amendment Space Rent
                  Commencement Date, with respect to the Original Leased
                  Premises, Tenant shall pay to Landlord as Additional Rent due
                  hereunder, for any Tax Year, any part of which shall occur
                  during the Term or any Extension Term, an amount (the "TAX
                  PAYMENT") equal to: (i) Tenant's Pro-Rata Share (as defined in
                  the Lease without reference to the First Amendment) of the
                  Taxes attributable to the land underlying the Building that
                  constitutes part of the Property and those portions of the
                  Building that do not constitute improvements made by, or on
                  behalf of Tenant or other tenants (collectively, the "BASE
                  BUILDING"), plus 100% of the Taxes attributable to the
                  Tenant's Work (as defined under the Lease without reference to
                  the First Amendment).

                           (ii) Commencing on the First Amendment Space Rent
                  Commencement Date with respect to the entire Leased Premises
                  including the Original Leased Premises and the First Amendment
                  Space, Tenant shall pay to Landlord as Additional Rent due
                  hereunder, for any Tax Year, any part of which occurs after
                  the First Amendment Space Rent 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
                  this Lease as amended by the First 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

                                       4

<PAGE>

                  Article 4, unless specified to the contrary, shall mean
                  Tenant's Work both as defined under this Lease and under the
                  First Amendment).

                           (iii) Landlord shall request the New Haven Tax
                  Assessor's informal opinion regarding apportionment of the
                  Taxes among the Base Building and the Tenant's Work in order
                  to calculate the Tax Payment due under subsections 4.2(a)(i)
                  and 4.2(a)(ii) above. Absent manifest error, the New Haven Tax
                  Assessor's opinion shall be binding on the parties. If the New
                  Haven Tax Assessor refuses to participate in such
                  apportionment, the Landlord shall make the initial
                  determination, and if Tenant disagrees therewith, Tenant shall
                  pay its portion of the Taxes in accordance with Landlord's
                  determination without prejudice, and shall otherwise have the
                  same right to audit and challenge Landlord's determination as
                  Tenant has with respect to Landlord's determination of the
                  Enterprise Zone benefit pursuant to Section 4(d) below.

                  (b) ENTERPRISE ZONE BENEFITS. Notwithstanding anything to the
                  contrary contained herein, Tenant shall be entitled to apply
                  for Enterprise Zone tax treatment with respect to the Tenant's
                  Work and the Building 5 Improvements, and Landlord shall
                  cooperate with Tenant in connection with any such application.
                  Tenant shall be entitled to 100% of the benefits available
                  from the Enterprise Zone program with respect to the Tenant's
                  Work and Tenant's Pro-Rata Share of the benefits available
                  from the Enterprise Zone program with respect to the Building
                  5 Improvements. All Enterprise Zone benefits to which Tenant
                  is entitled hereunder shall reduce the Tax Payments due from
                  Tenant hereunder. Landlord shall request the New Haven Tax
                  Assessor's opinion, formal or informal, regarding
                  apportionment of the Enterprise Zone tax benefits among the
                  Tenant's Work (with reference to the cost of the Tenant's
                  Work) and the Building 5 Improvements (with reference to the
                  cost of the Building 5 Improvements). Absent manifest error,
                  the New Haven Tax Assessor's opinion shall be binding on the
                  parties.

                  (c) APPORTIONMENT OF BENEFITS.If the New Haven Tax Assessor is
                  unable or unwilling to apportion the benefits of the
                  Enterprise Zone program to Tenant's Work separate and apart
                  from the Building 5 Improvements, Landlord, again with
                  reference to the cost of the Tenant's Work and the Building 5
                  Improvements, shall apportion the Enterprise Zone benefits
                  among the Tenant's Work and the Building 5 Improvements and
                  Tenant shall share in such benefits in accordance with the
                  provisions of subsection (b) above.

                  (d) AUDIT RIGHT. If Tenant disagrees with Landlord's
                  determination of the Enterprise Zone benefits attributable to
                  the Building 5

                                       5

<PAGE>

                  Improvements and/or to the Tenant's Work (in the absence
                  of a determination by the New Haven Tax Assessor), Tenant
                  shall pay its Taxes without prejudice, and may give
                  Landlord notice that it disputes Landlord's determination.
                  Within forty-five days following Landlord's receipt of such
                  notice, Tenant shall have the right to audit Landlord's
                  calculations. If the parties fail to agree on the correct
                  measure of Enterprise Zone benefit due Tenant, either party
                  may submit the dispute to binding arbitration under the
                  commercial leasing rules of the American Arbitration
                  Association with three (3) arbitrators, each having at least
                  ten (10) years of commercial real estate leasing experience in
                  New Haven County. If the arbitrators award Tenant Enterprise
                  Zone benefits that are three (3%) percent or greater than the
                  amount Tenant would have received under Landlord's original
                  determination, Landlord shall pay all costs of the
                  arbitration, including Tenant's reasonable attorneys fees,
                  otherwise, Tenant shall pay all costs of the arbitration
                  including Landlord's reasonable attorneys fees.

10.      TAX RELIEF. Section 4.4 of the Original Lease 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."

11.      THE BUILDING. The phrase "Building 5 North" in Section 11.4 of the
         Original Lease is replaced by the phrase "Building 5 North and Building
         5 South".

12.      PARKING. The rental of the First Amendment Space will include the use
         of twenty-five (25) parking spaces in addition to the eighty (80)
         parking spaces provided for under the Lease, for a total of one hundred
         five (105) parking spaces, all of which parking spaces shall be made
         available to Tenant as of the date Tenant takes occupancy of the First
         Amendment Space for the purpose of conducting its business therein. The
         term "TENANT'S PARKING SPACES" as used in the Lease shall mean said 105
         parking spaces, of which four (4) spaces shall be designated with
         signage as being reserved for Tenant's visitors. The four (4) spaces
         designated as Tenant's visitor parking shall be in addition to the
         fifteen (15) spaces reserved for Tenant's exclusive use pursuant to
         Section 1.2 of the Original Lease. Tenant's Parking Spaces shall be
         located in the areas shown on EXHIBIT A-4 attached hereto and made a
         part hereof. Tenant shall use Tenant's Parking Spaces in common with
         the other tenants of Science Park (except for its 15 reserved spaces
         and its visitor parking spaces which are for Tenant's exclusive use),
         but shall have the right to use all of Tenant's Parking Spaces within
         the areas shown on EXHIBIT A-4 at all times during the Term, and any
         Extension Term.

                                       6

<PAGE>

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

14.      LANDLORD'S WORK AND INTERIOR WORK.

                  (a) Pursuant to the provisions of Sections 2.4B, 2.4E - H and
         2.6 of the Lease, Landlord, at its expense, shall undertake the work
         described on EXHIBIT B-1 [CONTINUED] and EXHIBIT B-3 attached hereto
         and made a part hereof (collectively, the "LANDLORD'S WORK").

                  (b) As part of the Landlord's Work that Landlord is obligated
         to perform hereunder, Landlord hereby agrees to complete all of the
         work described on EXHIBIT B-3 attached hereto and made a part hereof
         (the "INTERIOR WORK"). Landlord hereby agrees to complete the
         Landlord's Work in a good and workmanlike fashion. Except as otherwise
         provided herein to the contrary, 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 First Amendment Space, except
         as otherwise expressly provided in the Lease, as modified by this First
         Amendment. Substantial completion of the Landlord's Work shall be
         evidenced by issuance of a certificate of occupancy. Landlord and
         Tenant shall each use their best efforts to collectively cause Fusco
         Corporation and Svigals Associates to coordinate the Interior Work with
         the Tenant's Work (as defined in Article 12 of this First Amendment)
         with respect to the First Amendment Space in order not to delay
         completion of the Tenant's Work with respect to the First Amendment
         Space. That portion of the Landlord's Work, not including the Interior
         Work, shall be finished pursuant to the existing time requirements for
         completion of the Landlord's Work under the Original Lease.

                  (c) It shall be Landlord's obligation to perform the Interior
         Work at Landlord's expense. Landlord shall use its best efforts to
         substantially complete all of the Interior Work by the First Amendment
         Space Rent Commencement Date. In addition, Landlord represents that all
         electrical, mechanical, plumbing and other building systems serving the
         First Amendment Space will be in working order on the First Amendment
         Space Rent Commencement Date. 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.

15.      TENANT'S WORK. Tenant, at Tenant's expense, agrees to make improvements
         to the First Amendment 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 Lease shall govern

                                       7

<PAGE>

         the approval of same. 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.

16.      LIMITATION ON LANDLORD'S LIABILITY. Notwithstanding anything to the
         contrary contained in the Lease or this First Amendment, if the Science
         Park Development Corporation transfers fee simple title to the
         Property, voluntarily or involuntarily, or if the Landlord converts
         from a non-profit to a profit organization, the Lease shall be amended
         by deleting Sections 11.3A and 11.3B in their entirety and substituting
         therefor the following:

                           A. Landlord shall not be liable to Tenant, and to the
                  fullest extent allowed by law, Tenant, for itself and its
                  employees, contractors, subcontractors, agents, licensees and
                  invitees hereby waives any and all claims, actions and causes
                  of action which they or any of them may have now or in the
                  future arising from Landlord's negligence including, without
                  limitation, claims for damages resulting from loss of life,
                  bodily injury or damage to any property on or about the
                  Property or the approaches, entrances, streets, sidewalks or
                  corridors thereto, except as herein otherwise provided and
                  except that the foregoing shall not apply in the event of
                  breach of this Lease by, or gross negligence of, and/or
                  willful misconduct of Landlord, its employees or agents.
                  Tenant shall promptly notify Landlord of any defective
                  condition in the Building of which it becomes aware.

                           B.  [INTENTIONALLY OMITTED]

17.      SUBORDINATION AND NON-DISTURBANCE. As used herein, the term "LANDLORD'S
         LENDERS" 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 First Amendment Space is a
         part. Tenant's obligations under this First Amendment are subject to
         receipt of non-disturbance agreements: (A) from CDA, simultaneously
         with the execution and delivery of this First 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 Lease. Provided CHFA and
         CDA execute and deliver said non-disturbance agreements, the Lease, as
         modified by this First 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 First Amendment
         Space, or the property of which the Leased Premises are a part, and (b)
         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 First Amendment Space, or the property of which the
         Leased Premises are a part. Tenant agrees to execute, at no expense to
         Landlord, any

                                       8

<PAGE>

         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 First Amendment, 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.

18.      NEW CII LOAN   A.Tenant has a commitment from CII for a new loan in the
         amount of $2,720,000 to finance construction of the Tenant's Work in
         both the First Amendment Space and other space in Building 5 South.
         Section 15.1B of the Lease is hereby modified to permit Tenant to
         assign its right, title and interest in and to the First 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 the First Amendment or
         to sublet the First Amendment 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.

         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 First Amendment Space, (b) verifying the nonexistence of
         any security interests in personal property and fixtures that form a
         part of the First Amendment Space, other than the rights therein, if
         any, of 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 First Amendment Space or any part
         thereof in derogation of Landlord's title. Upon the execution of this
         First 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.

19.      SIGNS. Article 28 of the Original Lease is hereby amended by
         designating same as subsection "A" and adding the following as a new
         second paragraph:

                  B. Notwithstanding anything to the contrary contained herein,
                  Tenant shall have the exclusive right to install a sign with
                  its name and logo on the outside of the Building that is
                  clearly visible from the streets bounding the Building.
                  Landlord shall have the right to approve such sign, and such
                  approval shall not be unreasonably

                                       9

<PAGE>

                  withheld. Tenant, at its sole cost and expense, shall be
                  responsible for obtaining any approvals required by applicable
                  law in connection with having any such sign, and shall remove
                  such signage at the expiration of the Term, as same may be
                  extended. Tenant, at its expense, shall use reasonable
                  diligence to restore the facade of the Building to the
                  condition it was in at the time Tenant installed the sign,
                  reasonable wear and tear and loss by fire or other casualty
                  excepted.

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

21.      HVAC SERVICE. The text of Article 36 of the Lease is hereby deleted and
         substituted therefor is the following:

         "A. Landlord, at its sole cost, shall operate the Building's boilers
         and chillers to supply hot and chilled water sufficient to operate
         Tenant's air-conditioning, heating and ventilating systems ("TENANT'S
         HVAC SYSTEM") and Landlord's heating, ventilating and cooling systems
         serving the common areas of the Building Monday through Friday from
         8:00 a.m. to 6:00 p.m. ("BUSINESS HOURS"). Landlord, at its expense,
         may install submeters or energy measuring devices (on the two chillers,
         the boilers, and on the hot and chilled water supply lines that serve
         Tenant's HVAC System) to measure the energy supplied to the Tenant's
         HVAC System. Landlord, at its expense, shall also operate the boilers
         and chillers to supply hot and chilled water to Tenant's HVAC System
         and other systems serving the said common areas outside Business Hours.
         Landlord's responsibility as to costs of operating the boilers and
         chillers outside of Business Hours shall be without regard to the
         requirement to supply Tenant's after-hours HVAC requirements and only
         to the extent required to maintain temperatures within the Building at
         off-hours setback points normal for an office building.

         B. If required for Tenant's laboratory requirements, Landlord shall
         operate the boilers and chillers 24 hours a day, 365 days a year to
         provide heated and chilled water to Tenant's HVAC System. Tenant shall
         reimburse Landlord as Additional Rent due hereunder for its share of
         the costs of energy to supply chilled or hot water outside of Business
         Hours over and above the costs for which Landlord is responsible absent
         a laboratory requirement pursuant to the last sentence of Section 36A
         hereof. Tenant's share of the costs of such after-Business Hours
         operation of the boilers and chillers shall be apportioned daily among
         those tenants using such services for HVAC outside of Business Hours on
         the basis of the floor areas of such tenants, after accounting for the
         basic off-hours needs of the Building to be attributed to the Landlord
         as set forth in the last sentence of Section 36A hereof. Alternatively,
         if Landlord installs an energy measuring system to track directly the
         energy supplied by the chillers and boilers to each of the tenants in
         the Building requiring hot and cold water outside of Business Hours,

                                       10

<PAGE>

         over and above the after-hours costs for which Landlord is responsible
         pursuant to Section 36A hereof, the cost of the energy used shall be
         computed and billed as Additional Rent based on actual utilization.

         C. Landlord's share of the cost of operation of the boilers and
         chillers outside of Business Hours shall be determined as promptly as
         possible after the date hereof by an impartial professional engineer
         selected by mutual agreement of Landlord and Tenant. Said engineer, at
         Landlord's expense, shall compute the share of energy costs for the
         Landlord to maintain the Building outside of Business Hours at normal
         office building temperatures absent laboratory use and under various
         weather and temperature conditions over a one-year period. The balance
         of the costs of such operation outside of Business Hours shall be
         apportioned proportionately among the Tenants requiring such services
         on the basis of the tenant's rentable square footage. If a direct
         energy measurement system is installed to track the after-Business
         Hours energy requirements of tenants in the Building, the engineer
         shall establish proper procedures for the utilization of said system so
         that Landlord and all tenants pay for their proper share of after-hours
         energy utilization. Landlord shall provide Tenant with a copy of the
         engineer's report as well as an opportunity to discuss details of the
         analysis and of the energy management system.

         D. Landlord shall bill Tenant monthly for its share of after-Business
         Hours operation of the boilers and chillers, commencing on the Rent
         Commencement Date with respect to the Original Leased Premises, and on
         the First Amendment Space Rent Commencement Date with respect to the
         First Amendment Space, throughout the Term as long as Tenant maintains
         a requirement for hot and chilled water outside of Business Hours. All
         such billings shall be accompanied by Landlord's calculation of
         Tenant's share of such cost for each month as well as the appropriate
         reports from metering and reporting devices.

22.      OPERATING EXPENSES. The Lease is hereby amended by adding a new Article
         37 as follows:

                         ARTICLE 37. OPERATING EXPENSES

         37.1     DEFINITIONS. As used in this Article, the following terms
                  shall have the following meanings:

                  (a) "First Amendment Space" shall have the same meaning as set
                  forth in the First Amendment to Lease.

                  (b) With respect to the First Amendment Space, "Base Expense
                  Year" shall mean the twelve month period commencing on the
                  date Tenant first occupies the First Amendment Space for
                  purposes of conducting its business therein.

                                       11

<PAGE>

                  (c) "Building" shall mean the entirety of Building 5 North and
                  Building 5 South of Science Park, including any below grade
                  portions thereof.

                  (d) "Operating Expense Year" shall mean each calendar year
                  following the Base Expense Year, all or any portion of which
                  falls within the Term of this Lease, as extended from time to
                  time. Notwithstanding the foregoing, the first Operating
                  Expense Year shall commence on the first day following the
                  expiration of the Base Expense Year and shall end on the
                  following December 31, and the last Operating Expense Year
                  shall end on the last day of the Term. Tenant's obligation
                  under this Article to pay estimated and actual amounts towards
                  Operating Expenses for the first and last Operating Expense
                  Year shall be prorated by multiplying the total estimated or
                  actual (as the case may be) Operating Expenses paid or
                  incurred during the first or last (as the case may be)
                  Operating Expense Year, as well as the total Operating
                  Expenses paid or incurred during the Base Expense Year, by a
                  fraction, the numerator of which shall be the number of days
                  in the first or last (as the case may be) Operating Expense
                  Year, and the denominator of which shall be 365.

                  (e) "Operating Expenses" shall mean all reasonable and
                  customary operating expenses (other than Taxes and Building 5
                  Improvements) incurred or borne by Landlord in connection with
                  the operation, maintenance and repair of Building 5 North and
                  Building 5 South and the Park Expenses (as hereinafter
                  defined) including:

                  1. Reasonable wages and salaries of all employees below the
                  level of manager engaged in the physical operation and/or
                  maintenance of the Building, including Landlord's portion of
                  social security taxes and any other taxes which may be levied
                  against Landlord on such wages and salaries.

                  2. Property management fees paid or incurred with respect to
                  the Building.

                  3. Costs incurred in connection with supply of electricity to
                  the common areas of the Building

                  4. Costs incurred in connection with the normal and customary
                  use by all tenants of the Building of all energy sources,
                  including gas, water and sewer and hot water charges (but not
                  including those amounts paid directly by Tenant pursuant to
                  this lease or by the tenants of the Building pursuant to their
                  leases).

                                       12

<PAGE>

                  5. The cost of janitorial and office supplies and similar
                  materials used in the operation and/or maintenance of the
                  Building.

                  6. The cost of all maintenance and services incurred in the
                  operation of the Building and all service agreements pursuant
                  thereto, including, but not limited to, protection and
                  security service, window cleaning, tenant area and common area
                  cleaning and janitorial service, plant and landscaping service
                  (to the extent not included in the Park Expenses) including
                  maintenance of the grounds, plantings and replantings (after
                  completion of the Building 5 Work), trash removal and
                  recycling pick-up.

                  7. Insurance premiums for liability, fire and loss of rents
                  insurance for the Building, and insurance premiums for both
                  Workers Compensation Insurance and Unemployment Compensation
                  Insurance covering employees below the level of manager to the
                  extent that their employment related activities are
                  attributable to operation of the Building.

                  8. The cost of all required non-structural repairs,
                  replacements and maintenance in the Building (in each case, to
                  the extent not covered by insurance, manufacturer's or
                  installer's warranties or condemnation proceeds), including
                  but not limited to, window glass, heating and cooling units
                  and systems, bathroom fixtures and all plumbing facilities,
                  all common area interior walls, floors and covering, utility
                  conduits and force mains, signs, elevators, sidewalks and
                  steps, all building service equipment, lighting units and
                  fixtures including bulb and tubes, all other building fixtures
                  and equipment, except to the extent any of the foregoing
                  repairs, replacements or maintenance is necessitated by the
                  acts or omissions of one tenant and except to the extent
                  excluded pursuant to Section 37.1(f) below.

                  9. Any costs incurred by Landlord for any capital
                  improvements, repairs or replacements, other modifications or
                  structural repairs to the Building (not attributable to latent
                  defects or the Building 5 Improvements), which are required by
                  a change in the law or a new law applicable to the Property
                  passed after the First Amendment Space Commencement Date with
                  respect to the First Amendment Space; the costs for any item
                  in this clause, (or series of related items, undertaken within
                  a reasonably short period of time, which, if taken together,
                  would reasonably constitute a single item) shall be amortized
                  over the maximum useful life of such item(s), in accordance
                  with the U.S. Internal Revenue Code and Regulations in effect
                  from time to time.

                                       13

<PAGE>

                  10. Any costs incurred by Landlord in making structural
                  repairs, capital improvements or other modifications to the
                  Building (which are not attributable to latent defects or the
                  Building 5 Improvements), which will reduce Operating
                  Expenses; the costs for any such item (or series of related
                  items, undertaken within a reasonably short period of time,
                  which, if taken together, would reasonably constitute a single
                  item) shall be amortized, over the maximum useful life of such
                  item(s), in accordance with the U.S. Internal Revenue Code and
                  Regulations in effect from time to time; provided however, any
                  required annual amortization amount will not exceed the
                  reduction in Operating Expenses realized by Tenant for the
                  relevant Operating Expense Year and the amortization schedule
                  will be extended beyond the maximum useful life, if necessary,
                  to fully amortize same.

                  (f) Notwithstanding anything to the contrary contained in the
                  Lease as amended, "Operating Expenses" and "Park Expenses" (as
                  hereinafter defined) shall not include:

                  1. Items which are the direct responsibility of any tenant or
                  are caused by the intentional or negligent act of any tenant,
                  its agents, licensees or business invitees;

                  2. Expenses of alterations to any portion of the Building for
                  the accommodation of a specific tenant or tenants;

                  3. All third party costs and expenses of leasing space in the
                  Building, including, without limitation, legal fees and
                  broker's commissions and advertising, and the salary of any
                  employee of Landlord dedicated exclusively to leasing space in
                  Science Park;

                  4. Costs actually covered by Landlord's insurance or other
                  manner of reimbursement and for which payment is received by
                  Landlord;

                  5. The cost of any capital improvement, repair or replacement
                  except as specifically provided in Sections 37.1(e) 9 and 10
                  above;

                  6. Cost attributable to the Building 5 Improvements;

                  7. Costs incurred due to Landlord violations of any of the
                  terms and conditions of any leases in the Building and/or
                  costs attributable to enforcing leases against tenants in the
                  Building, such as attorney's fees, court costs, adverse
                  judgments and similar expenses;

                                       14

<PAGE>

                  8. Overhead and profit paid to subsidiaries or affiliates of
                  the Landlord for management services or materials to the
                  extent that the costs of those items would not have been paid
                  had the services and materials been provided by unaffiliated
                  parties on a competitive basis;

                  9. Debt service on any mortgages of the Landlord and rental
                  under any ground or underlying lease and charges and fees
                  incurred by Landlord in connection with the procurement and
                  recording of any such mortgage or ground or underlying lease,
                  and amortization of debt;

                  10. Repairs and other work occasioned by fire, or other
                  casualty or condemnation, whether or not the Landlord is
                  reimbursed by insurance proceeds or condemnation award;

                  11. Any costs, fines or penalties incurred due to violations
                  by Landlord of any governmental rule or authority and the
                  defense of same;

                  12. All items and services for which Landlord is reimbursed
                  under other leases for space in the Building, or under other
                  provisions of this Lease; and/or

                  13. Notwithstanding anything to the contrary herein set forth,
                  the cost of any environmental remediation, monitoring,
                  cleanup, testing, reporting, investigation or study, or any
                  damages payable by Landlord.

                  (g) "Controllable Operating Expenses" shall mean all Park
                  Expenses and all Operating Expenses, except for the cost of
                  utility charges (electricity, gas, water and sewer) and
                  insurance included in the definition of Operating Expenses.

                  (h) "Operating Expense Cap" shall mean that Tenant shall not
                  be charged for any increase in Controllable Operating Expenses
                  in excess of five (5%) percent over the Controllable Operating
                  Expenses for the Base Expense Year, with respect to the first
                  Operating Expense Year, or in excess of five (5%) percent over
                  the Controllable Operating Expenses for the immediately
                  preceding Operating Expense Year, with respect to each
                  succeeding Operating Expense Year.

                  (i) "Tenant's OE Share" with respect to the First Amendment
                  Space shall mean a fraction, the numerator of which shall be
                  the total number of rentable square feet in the First
                  Amendment Space and the

                                       15

<PAGE>

                  denominator of which shall be the total number of rentable
                  square feet in the Building, which Landlord represents is
                  currently 102,938 rentable square feet.

                  (j) "Park Expenses" shall mean a fraction (equal to the
                  rentable area of the Building divided by the rentable area of
                  all buildings then owned by Landlord in Science Park including
                  Buildings 4, 5 and 25) of the reasonable and customary
                  overhead, administrative and operating expenses (other than
                  Operating Expenses that are not Park Expenses, Taxes and
                  Building 5 Improvements) incurred or borne by Landlord in
                  connection with the operation and maintenance of the Property
                  (as defined in Section 1.1 of the Original Lease) and
                  including, without limitation, employee salaries up to and
                  including the level of building manager, together with the
                  reasonable salary of the executive director of the Landlord
                  (subject to the provisions of Section 37.2 hereof), security
                  guard services, snow plowing of the driveways and parking
                  areas and landscaping maintenance. Landlord hereby represents
                  that currently the said fraction described above is equal to
                  approximately 30.00%.

         37.2     GROSS-UP PROVISION. If the Building is not fully occupied
                  during all or a portion of the Base Expense Year, Landlord
                  shall, in accordance with sound accounting and management
                  practices, determine the amount of Operating Expenses that
                  would have been included in the 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
                  Base Expense Year. In addition, if the Building is not fully
                  occupied during all or a portion of any Operating Expense
                  Year, Landlord may, in accordance with sound accounting and
                  management practices, determine the amount of Operating
                  Expenses that would have been paid or incurred had the
                  Building been fully occupied, and the amount so determined
                  shall be deemed to have been the amount of Operating Expenses
                  for such year. Notwithstanding anything to the contrary
                  contained herein, once the Landlord hires an Executive
                  Director, the reasonable salary of the Executive Director
                  shall be added to the Park Expenses included in each Base
                  Expense Year.

         37.3     OPERATING EXPENSE PAYMENTS. In addition to Base Rent and other
                  Additional Rent due and payable by Tenant pursuant to the
                  other provisions of this Lease, Tenant shall pay to Landlord ,
                  as Additional Rent, commencing in the fifth (5th) Operating
                  Expense Year, an amount equal to Tenant's OE Share of the
                  amount of Operating Expenses paid or incurred by Landlord
                  during each Operating Expense Year in excess of the amount of
                  Operating Expenses paid or

                                       16

<PAGE>

                  incurred by Landlord during the Base Expense Year; provided,
                  however, that for purposes of the calculations made under this
                  Article: (i) in no event shall Tenant be charged for Operating
                  Expenses in excess of the Operating Expense Cap; and (ii) in
                  no event shall Landlord charge Tenant more than Tenant's OE
                  Share of 100% of the actual cost of Operating Expenses
                  incurred by Landlord. Operating Expenses for partial Operating
                  Expense Years shall be divided by the number of months in such
                  partial year and multiplied by twelve (12) for purposes of
                  determining whether the Operating Expense Cap has been
                  exceeded.

         37.4     ESTIMATED OE PAYMENTS. Additional Rent due and payable by
                  Tenant to Landlord pursuant to this Article shall be paid in
                  the following manner:

                  (a) Landlord shall reasonably estimate in advance the amounts
                  Tenant shall owe under this Article for any full or partial
                  Operating Expense Year. Beginning in the fifth Operating
                  Expense Year, Tenant shall pay such estimated amounts, on a
                  monthly basis, on or before the first day of each calendar
                  month during the fifth and each following Operating Expense
                  Year. Such estimate may be reasonably adjusted from time to
                  time by Landlord.

                  (b) Within 120 days after the end of each Operating Expense
                  Year, or as soon thereafter as practicable, Landlord shall
                  provide a statement (the "STATEMENT") to Tenant showing: (i)
                  the amount of actual Operating Expenses for such Operating
                  Expense Year, with a listing of amounts for major categories
                  of Operating Expenses, and such amounts for the Base Expense
                  Year, (ii) any amount paid by Tenant towards Additional Rent
                  payable under this Article during such Operating Expense Year
                  on an estimated basis, (iii) any revised estimate of Tenant's
                  obligations for Operating Expenses for the current Operating
                  Expense Year, and (iv) a calculation of whether the Operating
                  Expense Cap has been exceeded.

                  (c) If the Statement shows that the estimated payments made by
                  Tenant during the Operating Expense Year were less than
                  Tenant's actual obligations for the payment of Additional Rent
                  under this Article for such Year, Tenant shall pay the
                  difference. If the Statement shows an increase in Tenant's
                  estimated payments for the current Operating Expense Year,
                  Tenant shall pay the difference between the new and former
                  estimates, for the period from the first day of the
                  then-current Operating Expense Year through the month in which
                  the Statement is sent, subject to the Operating Expense Cap.

                                       17

<PAGE>

                  Tenant shall make such payments within thirty (30) days after
                  the Statement is deemed to have been given under the terms of
                  this Lease.

                  (d) If the Statement shows that Tenant's estimated payments
                  exceeded Tenant's actual obligations for the payment of
                  Operating Expenses under this Article, or if for some reason
                  Tenant's estimated payments exceeded the Operating Expense
                  Cap, then Tenant shall receive a credit for the difference
                  against payments of rent next due. If the Term shall have
                  expired and no further rent shall be due, Tenant shall receive
                  a refund of such difference, within sixty (60) days after
                  Landlord sends the Statement. Notwithstanding anything to the
                  contrary contained herein, if Tenant's estimated payments
                  would cause the Operating Expense Cap to be exceeded, Tenant
                  shall only be obligated to make estimated payments up to the
                  Operating Expense Cap with respect to each Operating Expense
                  Year.

                  (e) No delay by Landlord of nine (9) months or less in
                  providing the Statement (or separate statements) shall be
                  deemed a default by Landlord or a waiver of Landlord's right
                  to require payment of Tenant's obligations under this Article.
                  After such nine (9) month period, Landlord shall be estopped
                  from billing for past Operating Expenses. In no event shall a
                  decrease in Operating Expenses below the Base Expense Year
                  amount ever decrease the monthly Base Rent, or give rise to a
                  credit in favor of Tenant.

         37.5     BOOKKEEPING AND AUDITING. Landlord shall maintain records
                  respecting Operating Expenses and determine the same in
                  accordance with sound accounting and management practices,
                  consistently applied. Tenant or its representative shall have
                  the right to examine those books and records of Landlord and
                  any managing agent reasonably necessary for purposes of
                  auditing the Statement in question, provided Tenant gives
                  Landlord reasonable prior notice specifying the particular
                  respects in which the Statement is claimed to be incorrect.
                  Such examination shall take place during normal business hours
                  at the place or places where such records are normally kept
                  with forty-five (45) days following such notice from Tenant.
                  Each Statement shall be considered final, except as to matters
                  to which exception is taken after examination of Landlord's
                  records in the foregoing manner and within the foregoing
                  times. If Tenant takes exception to any matter contained in
                  the Statement as provided herein, Landlord shall refer the
                  matter to an independent certified public accounting firm
                  having a national practice, whose certification as to the
                  proper amount shall be final and conclusive as between
                  Landlord and Tenant. Tenant shall promptly pay the cost of
                  such

                                       18

<PAGE>

                  certification unless such certification determines that Tenant
                  was overbilled by more than two (2%) percent. Pending
                  resolution of any such exceptions in the foregoing manner,
                  Tenant shall continue paying, without prejudice to Tenant's
                  position, Tenant's OE Share of the excess of Operating
                  Expenses paid or incurred during the applicable Operating
                  Expense Year over the applicable Base Expense Year in the
                  amounts determined by Landlord, subject to adjustment after
                  any such exceptions are so resolved, and subject to the
                  Operating Expense Cap.

         37.6     SURVIVAL. The parties obligations set forth in this Article 37
                  shall survive the expiration or earlier termination of this
                  Lease for a period of one year, but such survival shall not be
                  deemed to effect the waiver set forth in Section 37.4(e)
                  hereof.

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

24.      MERGER. All understandings, letters of intent or agreements between
         Tenant and Landlord, which predate this First 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 First Amendment shall be binding or effective. This
         First Amendment and the Lease are the sole and complete expression of
         the agreement between Landlord and Tenant as to the subject matter
         thereof.

25.      SEVERABILITY. If any of the provisions of this First 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 First 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.

26.      GOVERNING LAW. The laws of the State of Connecticut will govern the
         interpretation of this First Amendment.

27.      BINDING NATURE. This First 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 First Amendment or otherwise.

                                       19

<PAGE>

         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

                                       20

<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

                                       21

<PAGE>

                                   EXHIBIT A-1

                       FLOOR PLAN OF FIRST AMENDMENT SPACE
                          FIRST FLOOR BUILDING 5 NORTH

                                       22

<PAGE>

                             EXHIBIT A-2 [CONTINUED]

                       FLOOR PLAN OF FIRST AMENDMENT SPACE
                         THIRD FLOOR BUILDING FIVE NORTH

                                       23

<PAGE>

                                   EXHIBIT A-4

                           LOCATION OF PARKING SPACES

                                       24

<PAGE>

                             EXHIBIT B-1 [CONTINUED]

                       LANDLORD'S WORK - BUILDING 5 NORTH

1.       Building 5 North'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

                                       25

<PAGE>

                                   EXHIBIT B-3

                      INTERIOR WORK - FIRST AMENDMENT SPACE

1.       Piping and supply of chilled and hot water sufficient to operate
         Tenant's HVAC system will be installed up to the First Amendment 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.<PAGE>

                                                                  Exhibit 10.6

                        SECOND AMENDMENT TO LEASE BETWEEN

                      SCIENCE PARK DEVELOPMENT CORPORATION

                                       and

                        GENAISSANCE PHARMACEUTICALS, INC.

Date:  December __, 1999

<PAGE>

         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".

<PAGE>

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

                                       2
<PAGE>

                  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

                                       3
<PAGE>

                                    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

                                       4
<PAGE>

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.

                                       5
<PAGE>

                  (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

                                       6
<PAGE>

                  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

                                       7
<PAGE>

         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

                                       8
<PAGE>

         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

                                       9
<PAGE>

(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.

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00008-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00008-of-00352.parquet"}]]