Document:

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                                                                 EXHIBIT 10.49

                     FIRST AMENDMENT TO EMPLOYMENT AGREEMENT

         This First Amendment to Employment Agreement ("Amendment"), effective
as of July 28, 2000, is made by and between NANOGEN, INC., a Delaware
corporation (the "Company"), and CLARE BROMLEY, III (the "Executive").

                                    RECITALS

         WHEREAS, the Company and Executive have entered into an Employment
Agreement, dated October 29, 1999 (the "Employment Agreement"); and

         WHEREAS, the Company and Executive wish to amend the Employment
Agreement as described herein.

         NOW, THEREFORE, the Company and Executive, in consideration of the
mutual promises set forth herein, agree as follows:

                                      TERMS

1.       RENEWAL. In Article I, Section B RENEWAL, the last sentence of the
         second paragraph shall be amended to decrease the number of months from
         "18" to "6", during which the Executive shall be paid his salary and
         benefits after termination as described therein.

2.       SECTION 280G. In Article III, Section E SECTION 280G relating to
         restrictions on payments made pursuant to the Employment Agreement that
         may be considered "excess parachute payments" during Change of Control
         events as defined therein, shall be deleted in its entirety.

3.       REMAINDER OF AGREEMENT. The other terms and conditions contained in the
         Employment Agreement shall remain in effect pursuant to the Employment
         Agreement and such terms and conditions, where applicable, shall also
         govern this Amendment.

4.       GOVERNING LAW. This Amendment shall be construed in accordance with the
         laws of the State of California, notwithstanding its conflicts of law
         provisions.

5.       EXECUTIVE ACKNOWLEDGMENT. Executive acknowledges (a) that he has
         consulted with or has had the opportunity to consult with independent
         counsel of his own choice concerning this Amendment, and has been
         advised to do so by the Company, and (b) that he has read and
         understands this Amendment, is fully aware of its legal effect, and has
         entered into it freely based on his own judgment.

6.       COUNTERPARTS. This Amendment may be executed in one or more
         counterparts, all of which taken together constituted one and the same
         agreement.

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         Executed by the parties as of the day and year first above written.

                                   NANOGEN, INC.

                                   By:
                                          /s/Howard C. Birndorf
                                      --------------------------
                                            Howard C. Birndorf
                                            Chairman  and  Chief
                                            Executive Officer

                                   EXECUTIVE

                                         /s/Clare Bromley, III
                                   -----------------------------
                                            Clare Bromley, III<PAGE>

                                                                    EXHIBIT 10.4

                              ANIKA RESEARCH, INC.
                              160 New Boston Street
                                Woburn, MA 01801

                                 April 29, 1993

MedChem Products, Inc.
232 West Cummings Park
Woburn, MA 01801
Attn: Jonathan D. Donaldson, President
      and Chief Executive Officer

Gentlemen:

      This letter agreement is being sent to you to confirm our understanding
regarding payments to be made by Anika Research, Inc. ("Anika") to MedChem
Products, Inc. ("MedChem") in connection with the commercial sale of Anika's
hyaluronic acid ("HA") product called ORTHOVISC(TM) for the non-surgical
treatment of temporomandibular joint dysfunction ("TMJ Products"). In
consideration of MedChem's prior investment in the development of TMJ Products,
Anika has agreed to make the following payments ("Payments"), subject to the
limitations below, to MedChem:

            (a) Payments will equal three percent (3%) of the Net Sales (as
      defined below) of TMJ Products by Anika during a period: beginning on the
      date of the first commercial sale of TMJ Products and ending on February
      27, 1996; and

            (b) Payments will equal twelve percent (12%) of the Net Sales of TMJ
      Products by Anika following February 27, 1996.

      The Payments will be made to MedChem on January 15, April 15, July 15 and
October 15 of each year until Anika's obligation to make such Payments expires
in accordance with this agreement. Concurrently with each Payment, Anika will
provide to MedChem the number of units of TMJ Products sold by Anika during the
preceding fiscal quarter of MedChem (or part thereof).

      Anika will keep separate, true and accurate books and records respecting
all transactions related to this agreement in accordance with generally accepted
accounting practices consistently applied, which books and records shall be kept
and maintained so as to permit verification of the payments due MedChem under
this agreement. Anika shall maintain such books and records for a period of at
least three (3) years following the close of the fiscal year in which they
pertain.

      For purposes of determining the Payments to be made to . MedChem, "Net
Sales" shall mean Anika's aggregate gross invoice price from or on account of
the sale of TMJ Products, less: (i) trade and quantity discounts actually
allowed; (ii) returns, rebates and allowances

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actually allowed; (iii) transportation, shipping and insurance charges
separately stated on the invoice and paid by the customer; and (iv) sales and
excise taxes, foreign tariffs and duties.

      The Payments will be made to MedChem on all commercial sales of TMJ
Products following the grant by the U.S. Food and Drug Administration of a
pre-market approval for TMJ Products and shall continue until the earlier to
occur of (i) ten (10) years following the first commercial sale of TMJ Products
by Anika, and (ii) such time as Anika has made Payments to MedChem under this
agreement totalling $35 million. Furthermore, Anika's obligation to make
Payments to MedChem will cease if Anika appoints MedChem to be Anika's exclusive
distributor of TMJ Products in the United States. This agreement should not be
construed as an agreement or commitment by Anika to appoint MedChem as Anika's
exclusive distributor of TMJ Products.

      In the event that Anika reasonably believes that its obligation to make
the Payments under this agreement is materially impairing its ability to
effectively market and sell TMJ Products, Anika and MedChem agree to renegotiate
the terms of this agreement in good faith, provided that MedChem is under no
obligation to alter the amount or timing of the Payments.

      If this agreement is satisfactory to you, I would ask that you execute a
copy of this letter and return it to me.

                                        Sincerely yours,

                                        ANIKA RESEARCH, INC.

                                        By:/s/ DAVID A. SWANN
                                           ------------------
                                           David A. Swann
                                           Chairman of the Board,
                                           President and Chief Executive Officer

Agreed to and
Accepted this 29th
day of April, 1993:

MEDCHEM PRODUCTS, INC.

By: /s/ JONATHAN D. DONALDSON
    -------------------------
    Jonathan D. Donaldson
    President and Chief
    Executive Officer<PAGE>

                                                                    Exhibit 10.8
                      Cummings Properties Management, Inc.
                                  Standard Form

                                COMMERCIAL LEASE

      In consideration of the covenants herein contained, Cummings Properties
Management, Inc., hereinafter called LESSOR, does hereby lease to Anika
Research, Inc. (a MA corp.) 160 New Boston Street, Woburn, MA 01801 hereinafter
called LESSEE, the following described premises, hereinafter called the leased
premises: approximately 22,870 square feet at 233, 234, 236, 238 and 240 West
Cummings Park, Woburn, MA 01801

      TO HAVE AND HOLD the leased premises for a term of five (5) years
commencing at noon on February 28, 1996 and ending at noon on February 28, 2001
unless sooner terminated as herein provided. LESSOR and LESSEE now covenant and
agree that the following terms and conditions shall govern this lease during the
term hereof and for such further time as LESSEE shall hold the leased premises.

      1. RENT. LESSEE shall pay to LESSOR base rent at the rate of three hundred
eight thousand seventy (308,070.00) U.S. dollars per year, drawn on a U.S. bank,
payable in advance in monthly installments of $25,672.50 on the first day in
each calendar month in advance, the first monthly payment to be made upon
LESSEE's execution of this lease, including payment in advance of appropriate
fractions of a monthly payment for any portion of a month at the commencement or
end of said lease term. All payments shall be made to LESSOR or agent at 200
West Cummings Park, Woburn, Massachusetts 01801, or at such other place as
LESSOR shall from time to time in writing designate. If the "Cost of Living" has
increased as shown by the Consumer Price Index (Boston, Massachusetts, all
items, all urban consumers), U.S. Bureau of Labor Statistics, the amount of base
rent due during each calendar year of this lease and any extensions thereof
shall be annually adjusted in proportion to any increase in the Index. All such
adjustments shall take place with the rent due on January 1 of each year during
the lease term. The base month from which to determine the amount of each
increase in the Index shall be January 1996, which figure shall be compared with
the figure for November 1996 and each November thereafter to determine the
percentage increase (if any) in the base rent to be paid during the following
calendar year. In the event that the Consumer Price Index as presently computed
is discontinued as a measure of "Cost of Living" changes, any adjustment shall
then be made on the basis of a comparable index then in general use.

      2. SECURITY DEPOSIT. LESSEE shall pay to LESSOR a security deposit in the
amount of fifty-one thousand (51,000.00) dollars upon the execution of this
lease by LESSEE**, which shall be held as security for LESSEE's performance as
herein provided and refunded to LESSEE without interest at the end of this lease
subject to LESSEE's satisfactory compliance with the conditions hereof. LESSEE
may not apply the security deposit to payment of the last month's rent. In the
event of any default or breach of this lease by LESSEE, LESSOR shall immediately
apply the security deposit first to any unamortized improvements completed for

--------
** and $25,500.00 on or before February 28, 1996

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LESSEE's occupancy, then to offset any outstanding invoice or other payment due
to LESSOR, with the balance applied to outstanding rent. If all or any portion
of the security deposit is applied to cure a default or breach during the term
of the lease, LESSEE shall be responsible for restoring said deposit forthwith
and failure to do so shall be considered a substantial default under the lease.
LESSEE's failure to remit the full security deposit or any portion thereof when
due shall also constitute a substantial lease default.

      3. USE OF PREMISES. LESSEE shall use the leased premises only for the
purpose of executive and administrative offices and research, development and
manufacturing of medical use products.

      4. ADDITIONAL RENT. LESSEE shall pay to LESSOR as additional rent a
proportionate share (based on square footage leased by LESSEE as compared with
the total leaseable square footage of the building of which the leased premises
are a part) of any increase in the real estate taxes levied against the land and
building of which the leased premises are a part, whether such increase is
caused by an increase in the tax rate, or the assessment on the property, or a
change in the method of determining real estate taxes. LESSEE shall make payment
within thirty (30) days of written notice from LESSOR that such increased taxes
are payable, and any additional rent shall be prorated should the lease
terminate before the end of any tax year. The base from which to determine the
amount of any increase in taxes shall be the rate and the assessment in effect
as of July 1, 1995. In the event that said building was not assessed as a
completed building as of the aforementioned date, then the base assessment shall
be as of the first date when the building is assessed as a completed structure.

      5. UTILITIES. LESSOR shall provide equipment per LESSOR's building
standard specifications to heat the leased premises in season and to cool all
office areas between May 1 and November 1. LESSEE shall pay all charges for heat
and electricity used on the leased premises. LESSEE shall pay LESSOR for all
water and sewer use as determined by LESSOR either by a separate water meter
serving the leased premises, or as a proportionate share of water and sewer
charges for the entire building of which the leased premises are a part if not
separately metered, and LESSEE shall pay LESSOR a proportionate share of any
other fees and charges relating in any way to water or sewer use at the
building. No plumbing, construction or electrical work of any type shall be done
without LESSOR's prior written approval and the appropriate municipal permit.

      6. COMPLIANCE WITH LAWS. LESSEE acknowledges that no trade, occupation,
activity or work shall be conducted in the leased premises or use made thereof
which may be unlawful, improper, noisy, offensive, or contrary to any applicable
statute, regulation, ordinance or bylaw. LESSEE shall keep all employees working
in the leased premises covered with Worker's Compensation Insurance and shall
obtain any licenses and permits necessary for LESSEE's occupancy. LESSEE shall
be responsible for causing the leased premises and any alterations by LESSEE
which are allowed hereunder to be in full compliance with any applicable
statute, regulation, ordinance or bylaw.

      7. FIRE, CASUALTY, EMINENT DOMAIN. Should a substantial portion of the
leased premises, or of the property of which they are a part. be substantially
damaged by fire or other casualty, or be taken by eminent domain, LESSOR may
elect to terminate this lease. When such fire, casualty, or taking renders the
leased premises substantially unsuitable for their intended use, a just and
proportionate abatement of rent shall be made, and LESSEE may elect to

                                       2
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terminate this lease if: (a) LESSOR fails to give written notice within thirty
(30) days of intention to restore the leased premises, (b) LESSOR fails to
restore the leased premises to a condition substantially suitable for their
intended use within ninety (90) days of said fire, casualty or taking. LESSOR
reserves all rights for damages or injury to the leased premises for any taking
by eminent domain, except for damage to LESSEE's property or equipment.

      8. MAINTENANCE OF PREMISES. LESSOR will be responsible for all structural
maintenance of the leased premises and for the normal daytime maintenance of all
space heating and cooling. equipment, sprinklers, doors, locks, plumbing and
electrical wiring, but specifically excluding damage caused by the careless,
malicious, willful, or negligent acts of LESSEE or others, chemical, water or
corrosion damage from any source, arid maintenance of any non "building
standard" leasehold improvements. LESSEE agrees to maintain at its expense all
other aspects of the leased premises in the same condition as they are at the
commencement of the term or as they may be put in during the term of this lease,
normal wear and tear and damage by fire or other casualty only excepted, and
whenever necessary, to replace light bulbs, plate glass and other glass therein,
acknowledging that the leased premises are now in good order and the light bulbs
and glass whole. LESSEE will properly control or vent all solvents, degreasers,
smoke, odors, etc. and shall not cause the area surrounding the leased premises
to be in anything other than a neat and clean condition, depositing all waste in
appropriate receptacles. LESSEE shall be solely responsible for any damage to
plumbing equipment, sanitary lines, or any other portion of the building which
results from the discharge or use of any acid or corrosive substance by LESSEE.
LESSEE shall not permit the leased premises to be overloaded. damaged, stripped
or defaced, nor suffer any waste, and will not keep animals within the leased
premises. If the leased premises include any wooden mezzanine type space, the
floor capacity of such space is suitable only for office use, light storage or
assembly work. If the leased premises are carpeted or partially carpeted. LESSEE
will protect carpet with plastic or masonite chair pads under any rolling
chairs. Unless heat is provided at LESSOR's expense, LESSEE shall maintain
sufficient heat to prevent freezing of pipes or other damage. Any increase in
air conditioning equipment or electrical capacity, or any installation and/or
maintenance of equipment which is necessitated by some specific aspect of
LESSEE's use of the leased premises shall be at LESSEE's expense. All
maintenance provided by LESSOR shall be during LESSOR's normal business hours.

      9. ALTERATIONS. LESSEE shall not make structural alterations or additions
of any kind to the leased premises, but may make nonstructural alterations
provided LESSOR consents thereto in writing.*** All such allowed alterations
shall be at LESSEE's expense and shall conform with LESSOR's construction
specifications. If LESSOR provides any services or maintenance for LESSEE in
connection with such alterations or otherwise under this lease, any just invoice
will be promptly paid. LESSEE shall not permit any mechanics' liens, or similar
liens, to remain upon the leased premises in connection with work of any
character performed or claimed to have been performed at the direction of LESSEE
and shall cause any such lien to be released or removed forthwith without cost
to LESSOR. Any alterations or additions shall become part of the leased premises
and the property of LESSOR. Any alterations completed by LESSOR shall be
LESSOR's "building standard" unless noted otherwise. LESSOR shall have the right
at any time to change the arrangement of parking areas, stairs, walkways or
other

------------
*** such consent shall not be unreasonably withheld

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common areas of the building of which the leased premises are a pany of such
consent shall not be unreasonably withheld.

      10. ASSIGNMENT OR SUBLEASING. LESSEE shall not assign this lease or sublet
or allow any other firm or individual to occupy the whole or any part of the
leased premises without LESSOR'S prior written consent. Notwithstanding such
assignment or subleasing. LESSEE and GUARANTOR shall remain liable to LESSOR for
the payment of all rent and for the full performance of the covenants and
conditions of this lease. LESSEE shall pay LESSOR promptly for legal and
administrative expenses incurred by LESSOR in connection with any consent
requested hereunder by LESSEE.

      11. SUBORDINATION. This lease shall be subject and subordinate to any and
all mortgages and other instruments in the nature of a mortgage, now or at any
time hereafter, and LESSEE shall, when requested, promptly execute and deliver
such written instruments as shall be necessary to show the subordination of this
lease to said mortgages or other such instruments in the nature of a mortgage.

      12. LESSOR'S ACCESS. LESSOR or agents of LESSOR may at any reasonable time
enter to view the leased premises, to make repairs and alterations as LESSOR
should elect to do for the leased premises, the common areas or any other
portions of the building of which the leased premises are a part, to make
repairs which LESSEE is required but has failed to do, and to show the leased
premises to others.

      13. SNOW REMOVAL. The plowing of snow from all roadways, access ways and
unobstructed parking and loading areas shall be at the sole expense of LESSOR.
The control of snow and ice on all steps serving the leased premises and all
other areas not readily accessible to plows shall be the sole responsibility of
LESSEE. Notwithstanding the foregoing, however. LESSEE shall hold LESSOR and
OWNER harmless from any and all claims by LESSEE's agents, representatives,
employees, callers or invitees for damage or personal injury resulting in any
way from snow or ice on any area serving the leased premises.

      14. ACCESS AND PARKING. LESSEE shall have the right without additional
charge to use parking facilities provided for the leased premises in common with
others entitled to the use thereof. Said parking areas plus any stairs,
walkways, elevators or other common areas shall in all cases be considered a
part of the leased premises to the extent that they are utilized by LESSEE, or
LESSEE'S employees, agents, callers or invitees. LESSEE will not obstruct in any
manner any portion of the building or the walkways or approaches to said
building, and will conform to all rules and regulations now or thereafter made
by LESSOR for parking, and for the care, use, or alteration of the building, its
facilities and approaches. LESSEE further warrants that LESSEE will not permit
any employee or visitor to violate this or any other covenant or obligation of
LESSEE. No unattended parking will be permitted between 7:00 PM and 7:00 AM
without LESSOR'S prior written approval, and from December 1 through March 31
annually, such parking shall be permitted only in those areas specifically
designated for assigned overnight parking. Unregistered or disabled vehicles, or
storage trailers of any type, may not be parked at any time. LESSOR may tow, at
LESSEE'S sole risk and expense, any misparked vehicle belonging to LESSEE or
LESSEE'S agents, employees, invitees or callers, at any time. LESSOR shall not
be responsible for providing any security services for the leased premises.

      15. LESSEE'S LIABILITY AND INSURANCE. LESSEE shall be solely responsible
as between LESSOR and LESSEE for deaths or personal injuries to all persons

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whomsoever occurring in or on the leased premises (including any extension
thereof) from whatever cause arising and damage to property to whomsoever
belonging arising out of the use, control, condition or occupation of the leased
premises by LESSEE; and LESSEE agrees to indemnify and save harmless LESSOR and
OWNER from any and all liability, including but not limited to expenses, damage,
causes of action, suits, claims or judgments caused by or in any way growing out
of any matters aforesaid except for death, personal injuries or property damage
directly resulting from the sole negligence of LESSOR. LESSEE will secure and
carry at its own expense a comprehensive general liability policy insuring
LESSEE, LESSOR and OWNER against any claims based on bodily injury (including
death) or property damage arising out of the condition of the leased premises or
their use by LESSEE, such policy to insure LESSEE, LESSOR and OWNER against any
claim up to One Million (1,000,000) Dollars in the case of any one accident
involving bodily injury (including death), and up to One Million (1,000,000)
Dollars against any claim for damage to property. LESSOR and OWNER shall be
included in each such policy as additional insureds. LESSEE will file with
LESSOR prior to occupancy certificates and any applicable riders or endorsements
showing that such insurance is in force, and thereafter will file renewal
certificates prior to the expiration of any such policies. All such insurance
certificates shall provide that such policies shall not be cancelled without at
least ten (10) days prior written notice to each insured. In the event LESSEE
shall fail to provide or maintain such insurance at any time during the term of
this lease, then LESSOR may elect to contract for such insurance at LESSEE's
expense.

      16. FIRE INSURANCE. LESSEE shall not permit any use of the leased premises
which will adversely affect or make voidable any insurance on the property of
which the leased premises are a part. or on the contents of said property. or
which shall be contrary to any law or regulation from time to time established
by the Insurance Services Office (or successor), local Fire Department, LESSOR's
insurer, or any similar body. LESSEE shall on demand reimburse LESSOR, and all
other tenants, all extra insurance premiums caused by LESSEE'S use of the leased
premises. LESSEE shall not vacate the leased premises or permit same to be
unoccupied other than during LESSEE'S customary non-business days or hours.

      17. BROKERAGE. LESSEE warrants and represents to LESSOR that LESSEE has
dealt with no broker or third person with respect to this lease and LESSEE
agrees to indemnify LESSOR against any brokerage claims arising by virtue of
this lease. LESSOR warrants and represents to LESSEE that LESSOR has employed no
exclusive broker or agent in connection with the letting of the leased premises.

      18. SIGNS. LESSOR authorizes, and LESSEE at LESSEE'S expense agrees to
erect, signage for the leased premises in accordance with LESSOR'S building
standards for style, size, location, etc. LESSEE shall obtain the prior written
consent of LESSOR before erecting any sign on the leased premises, which consent
shall include approval as to size, wording, design and location. LESSOR may
remove and dispose of any sign not approved, erected or displayed in conformance
with this lease.

      19. DEFAULT AND ACCELERATION OF RENT. In the event that: (a) LESSEE shall
default in the observance or performance of any of LESSEE's covenants,
agreements, or obligations hereunder other than substantial monetary payments as
provided below, and such default shall not be corrected within thirty (30) days
after written notice thereof; or (b) LESSEE vacates the leased premises, then
LESSOR shall have the right thereafter, while such default continues and without
demand or further notice, to re-enter and take possession of the leased

                                       5
<PAGE>

premises, to declare the terms of this lease ended, and to remove LESSEE's
effects, without being guilty of any manner of trespass, and without prejudice
to any remedies which might be otherwise used for arrears of rent or other
default ar breach of the lease. If LESSEE shall default in the payment of the
security deposit, rent, taxes, or any substantial invoice for goods and/or
services or other sum herein specified, and such default shall continue for ten
(10) days after written notice thereof, and, because both parties agree that
nonpayment of said sums when due is a substantial breach of the lease, and,
because the payment of rent in monthly installments is for the sole benefit and
convenience of LESSEE, then in addition to the foregoing remedies the entire
balance of rent which is due hereunder shall become immediately due and payable
as liquidated damages. LESSOR, without being under any obligation to do so and
without thereby waiving any default, may remedy same for the account and at the
expense of LESSEE. If LESSOR pays or incurs any obligations for the payment of
money in connection therewith, such sums paid or obligations incurred plus
interest and costs, shall be paid to LESSOR by LESSEE as additional rent. Any
sums received by LESSOR from or on behalf of LESSEE at any time shall be applied
first to any unamortized improvements completed for LESSEE's occupancy, then to
offset any outstanding invoice or other payment due to LESSOR, with the balance
applied to outstanding rent. LESSEE agrees to pay reasonable attorney's fees
and/or administrative costs incurred by LESSOR in enforcing any or all
obligations of LESSEE under this lease at any time. LESSEE shall pay LESSOR
interest at the rate of eighteen (18) percent per annum on any payment from
LESSEE to LESSOR which is past due.

      20. NOTICE. Any notice from LESSOR to LESSEE relating to the leased
premises or to the occupancy thereof shall be deemed duly served when left at
the leased premises addressed to LESSEE, or served by constable, or sent to the
leased premises by certified mail, return receipt requested, postage prepaid,
addressed to LESSEE. Any notice from LESSEE to LESSOR relating to the leased
premises or to the occupancy thereof shall be deemed duly served when served by
constable, or delivered to LESSOR by certified mail, return receipt requested,
postage prepaid, addressed to LESSOR at 200 West Cummings Park, Woburn, MA 01801
or at LESSOR'S last designated address. No oral notice or representation shall
have any force or effect. Time is of the essence in service of any notice.

        21. OCCUPANCY. In the event that LESSEE takes possession of said leased
premises prior to the start of said term. LESSEE will perform and observe all of
LESSEE's covenants from the date upon which LESSEE takes possession except the
obligation for the payment extra rent to any period of less than one month.
LESSEE shall not remove LESSEE's goods or property from the leased premises
other than in the ordinary and usual course of business, without having first
paid and satisfied LESSOR for all rent which may become due during the entire
term of this lease. In the event that LESSEE continues to occupy or control all
or any part of the leased premises after the agreed termination of this lease
without the written permission of LESSOR, then LESSEE shall be liable to LESSOR
for any and all loss, damages or expenses incurred by LESSOR, and all other
terms of this lease shall continue to apply except that rent shall be due in
full monthly installments at a rate of one hundred fifty (150) percent of that
which would otherwise be due under this lease, it being understood between the
parties that such extended occupancy is as a tenant at sufferance and is solely
for the benefit and convenience of LESSEE and as such has greater rental value.
LESSEE's control or occupancy of all or any part of the leased premises beyond
noon on the last day of any monthly rental period shall constitute LESSEE's
occupancy for an entire additional month, and increased rent as provided in this
section shall be due and payable immediately in advance. LESSOR's acceptance

                                       6
<PAGE>

of any payments from LESSEE during such extended occupancy shall not alter
LESSEE's status as a tenant at sufferance.

      22. FIRE PREVENTION. LESSEE agrees to use every reasonable precaution
against fire and agrees to provide and maintain approved, labeled fire
extinguishers, emergency lighting equipment, and exit signs and complete any
other modifications within the leased premises as required or recommended by the
Insurance Services Office (or successor organization), OSHA, the local Fire
Department, or any similar body.

      23. OUTSIDE AREA. No goods, equipment, or things of any type or
description shall be held or stored outside the leased premises at any time
without prior written consent from LESSOR. Any goods, equipment or things left
outside the leased premises without LESSOR's prior written consent shall be
deemed abandoned and may be removed at LESSEE's expense without notice by
LESSOR. A single two-yard capacity dumpsters hereby authorized for the disposal
of trash, provided that the location of said receptacle is approved by LESSOR.
LESSEE agrees to have said container provided and serviced at its expense by
whichever disposal firm may from time to time be designated by LESSOR. If a
dumpster is provided on a shared cost basis. LESSEE shall pay its proportionate
share of the costs associated with said dumpster.

      24. ENVIRONMENT. LESSEE will so conduct and operate the leased premises as
not to interfere in any way with the use and enjoyment of other portions of the
same or neighboring buildings by others by reason of odors, smoke, smells,
noise, pets, accumulation of garbage or trash, vermin or other pests, or
otherwise, and will at its expense employ a professional pest control service if
necessary. LESSEE agrees to maintain efficient and effective devices for
preventing damage to heating equipment from solvents, degreasers, cutting oils,
propellants, etc. which may be present at the leased premises. No hazardous
materials or wastes shaft be stored, disposed of, or allowed to remain at the
leased premises at any time*, and LESSEE shall be solely responsible for any and
all corrosion or other damage associated with the use, storage and/or disposal
of same by LESSEE.

      25. RESPONSIBILITY. Neither LESSOR nor OWNER shall be held liable to
anyone or loss for damage caused in any way by the use, leakage, seepage or
escape of water from any source, or for the cessation of any service rendered
customarily to said premises or buildings, or agreed to by the terms of this
lease, due to any accident, the making of repairs, alterations or improvements,
labor difficulties, weather conditions, mechanical breakdowns, trouble or
scarcity in obtaining fuel, electricity, service or supplies from the sources
from which they are usually obtained for said building, or any cause beyond
LESSOR's immediate control.

      26. SURRENDER. LESSEE shall at the termination of this lease remove all of
LESSEE's goods and effects from the leased premises. LESSEE shall deliver to
LESSOR the leased premises and all keys and locks thereto, all fixtures and
equipment connected therewith, and all alterations, additions and improvements
made to or upon the leased premises, whether completed by LESSEE, LESSOR or
others, including but not limited to any offices, partitions, window blinds,
floor coverings (including computer floors), plumbing and plumbing fixtures, air
conditioning equipment and ductwork of any type, exhaust fans or heaters, water
coolers, burglar alarms, telephone wiring, air or gas distribution piping,
compressors. overhead cranes, hoists, trolleys or conveyors, counters, or signs
attached to walls or floors, all electrical work, including

----------------
* except as provided in the Rider to Lease

                                       7
<PAGE>

but not limited to lighting fixtures of any type, wiring, conduit, EMT,
transformers, distribution panels, bus ducts, raceways, outlets and disconnects,
and furnishings or equipment which have been bolted, welded, nailed, screwed,
glued or otherwise attached to any wall, floor or ceiling, or which have been
directly wired to any portion of the electrical system or which have been
plumbed to the water supply, drainage or venting systems serving the leased
premises. LESSEE shall deliver the leased premises sanitized from any chemicals
or other contaminants, and broom clean and in the same condition as they were at
the commencement of this lease or any prior lease between LESSOR and MedChem
Products, Inc. for the leased premises, or as they were modified during said
term with LESSOR's written consent, reasonable wear and tear and damage by fire
or other casualty only excepted. In the event of LESSEE's failure to remove any
of LESSEE's property from the leased premises upon termination of the lease.
LESSOR is hereby authorized, without liability to LESSEE for loss or damage
thereto, and at the sole risk of LESSEE, to remove and store any such property
at LESSEE's expense, or to retain same under LESSOR's control, or to sell at
public or private sale (without notice), any or all of the property not so
removed and to apply the net proceeds of such sale to the payment of any sum due
hereunder, or to destroy such abandoned property. In no case shall the leased
premises be deemed surrendered to LESSOR until the termination date provided
herein or such other date as may be specified in a written agreement between the
parties, notwithstanding the delivery of any keys to LESSOR.

      27. GENERAL. (a) The invalidity or unenforceability of any provision of
this lease shall not affect or render invalid or unenforceable any other
provision hereof. (b) The obligations of this lease shall run with the land, and
this lease shall be binding upon and inure to the benefit of the parties hereto
and their respective successors and assigns, except that LESSOR and OWNER shall
be liable only for obligations occurring while lessor, owner, a master lessee of
the premises. (c) Any action or proceeding arising out of the subject matter of
this lease shall be brought by LESSEE within one year after the cause of action
has occurred and only in a court of the Commonwealth of Massachusetts. (d) If
LESSOR is acting under or as agent for any trust or corporation, the obligations
of LESSOR shall be binding upon the trust or corporation, but not upon any
trustee, office,. director, shareholder, or beneficiary of the trust or
corporation individually. (e) If LESSOR is not the owner (OWNER) of the leased
premises, LESSOR represents that said OWNER has agreed to be bound by the terms
of this lease unless LESSEE is in default hereof. (f) This lease is made and
delivered in the Commonwealth of Massachusetts, and shall be interpreted,
construed, and enforced in accordance with the laws thereof. (g) This lease was
the result of negotiations between parties of equal bargaining strength, and
when executed by both parties shall constitute the entire agreement between said
parties. No other oral or written representation shall have any effect hereon,
and this agreement may not be altered, extended or amended except by written
agreement attached hereto or as otherwise provided herein. (h) Notwithstanding
any other statements herein, LESSOR makes no warranty, express or implied,
concerning the suitability of the leased premises for LESSEE's intended use. (i)
LESSEE agrees that if LESSOR does not deliver possession of the leased premises
as herein provided for any reason, LESSOR shall not be liable for any damages to
LESSEE for such failure, but LESSOR agrees to use reasonable efforts to deliver
possession to LESSEE at the earliest possible date, and a proportionate
abatement of rent for such time as LESSEE may be deprived of possession of said
leased premises shall be LESSEE's sole remedy. (j) Neither the submission of
this lease form, nor the prospective acceptance of the security deposit and/or
rent shall constitute a reservation of or option for the leased premises, or an
offer to lease, it being

                                       8
<PAGE>

expressly understood and agreed that this lease shall not bind either pany in
any manner whatsoever until it has been executed by both parties. (k) LESSEE
shall not be entitled to exercise any option contained herein if LESSEE is in
default of any terms or conditions hereof. (l) The headings in this lease are
for convenience only and shall not be considered part of the terms hereof. (m)
No endorsement by LESSEE on any check shall bind LESSOR in any way.

      28. SECURITY AGREEMENT. THIS PARAGRAPH DOES NOT APPLY

      29. WAIVERS, ETC. No consent or waiver, express or implied, by LESSOR, to
or of any breach of any covenant, condition or duty of LESSEE shall be construed
as a consent or waiver to or of any other breach of the same or any other
covenant, condition or duly. If LESSEE is several persons, several corporations
or a partnership, LESSEE's obligations are joint or partnership and also
several. Unless repugnant to the context, `LESSOR" and "LESSEE" mean the person
or persons, natural or corporate, named above as LESSOR and as LESSEE
respectively, and their respective heirs, executors. administrators, successors
and assigns.

      30. AUTOMATIC FIVE-YEAR EXTENSIONS. This lease, including all terms,
conditions. escalations. etc. shall be automatically extended for additional
successive periods of five (5) years each unless LESSOR or LESSEE shall serve
written notice, either pany to the other, of either pany's desire not to so
extend the lease. The time for serving such written notice shall be not more
than twelve (12) months or less than six (6) months prior to the expiration of
the then current lease period. Time is of the essence.

      31. ADDITIONAL PROVISIONS. (Continued on attached rider it necessary.)

                              See Attached Rider -

      IN WITNESS WHEREOF. LESSOR AND LESSEE have hereunto set their hands and
common seals and intend to be legally bound hereby this 10th day of March, 1995.

LESSOR: CUMMINGS PROPERTIES MANAGEMENT, INC.    LESSEE: ANIKA RESEARCH, INC.

By: /s/ JAMES MCKEOWN                     By: /S/ SEAN MORAN
    -----------------                         --------------
    President                                 Sean Moran

                                                3/6/95

                                       9
<PAGE>

                                 RIDER TO LEASE

      The following additional provisions are incorporated into and made a part
of the attached lease:

A.    The leased premises consists of a total of approximately 22,820 square
      feet comprised of the following individual units: approximately 5,595
      square foot at 233 West Cummings Park; approximately 5,560 square feet at
      234 West Cummings Park; approximately 7,195 square foot at 236 West
      Cunnings Park; approximately 1,940 square foot at 238 West Cummings Park;
      and approximately 2,530 square fast at 240 West Cummings Park

B.    LESSOR and LESSEE acknowledge that Anika Research, Inc. has been occupying
      the leased premises as a subtenant of MedChem Products, Inc. LESSEE
      therefore now accepts the leased premises (specifically including but not
      limited to the underground hazardous substances storage system located
      under the paved area in front of the leased premises) from LESSOR in "as
      is" condition. LESSEE further represents and warrants that the leased
      premises are in satisfactory condition as of the execution date of this
      lease.

C.    LESSOR, as an expense incorporated entirely into the base rent and at no
      further cost to LESSEE, shall modify the leased premises according to a
      mutually agreed upon plan attached hereto about February 28, 1996. LESSEE
      shall have no further obligation to repay LESSOR for such modifications,
      notwithstanding anything to the contrary in this lease.

D.    With reference to Section 24 hereinabove, no hazardous materials or wastes
      shall be used, processed, stored, a disposed of in any manner or form
      within the leased premises or any extension thereof in violation of any
      applicable local, state, or federal law, rule or regulation. LESSEE shall
      be responsible for and shall indemnify and hold LESSOR harmless from any
      and all liability, damage or personal injury associated with any use,
      processing, storage, or disposal of such materials by LESSEE.

E.    The parties acknowledge and agree that the leased premises include the
      existing underground hazardous substances storage system referred to
      above, and LESSEE agrees to empty and clean said system in accordance with
      any laws, regulations and ordinances applicable thereto prior to the
      termination of the lease and provide LESSOR with a written report
      evidencing that said system has been emptied and cleaned in accordance
      with any laws, regulation and ordinances applicable thereto. In the event
      a governmental authority requires removal of said system on or before the
      termination of this lease, then LESSEE shall be solely responsible, at its
      sole cost and expense, for removal and any related work required by said
      governmental authority and for restoration of any affected areas,
      including any paving and landscaping; provided that LESSEE shall have the
      right to replace said system with another storage system as long as the
      replacement system is installed with LESSOR'S prior written approval, said
      approval not to be unreasonably withheld, and in accordance with all
      applicable laws, regulations and ordinances. If no governmental authority
      requires removal of the system before the termination of this lease,
      LESSOR may, in its sole discretion, require its removal by serving LESSEE
      with

                                       10
<PAGE>

      written notice to that effect within one (1) month alter the termination
      of this lease. In such event, LESSEE, at its sole cost and expense, shall
      remove said system in accordance with all applicable laws, regulations and
      ordinances, and shall restore any affected areas, including any paving and
      landscaping.

F.    LESSEE, at LESSEE'S sole expense, shall return the leased premises at the
      end of the lease term or any extension thereof free from any and all
      hazardous substances and wastes and biological, radiological, chemical or
      other contamination which, in any such case, is in violation of any
      applicable laws, regulations or ordinances and which, in any such case,
      has been placed on or about the leased premises by LESSEE. Prior to the
      end of the lease term, LESSEE shall be solely responsible for remedying
      any and all damage, removing any and all contamination and disposing of
      any hazardous substances and wastes caused or generated by LESSEE on or
      about the leased premises, to the extent such damage, contamination,
      substances and wastes are in violation of any applicable law. Time is of
      the essence.

G.    On or before the termination date of this lease, LESSEE, at LESSEES sole
      expense, shall engage an independent and accredited industrial hygiene
      consultant or other appropriate, accredited consultant to be selected by
      LESSEE with LESSOR's written consent said consent not to be unreasonably
      withheld or delayed, to inspect the interior of the leased premises. Said
      consultant shall state that, after reasonable investigation, no
      biological, radiological, chemical or other contamination generated in any
      way by LESSEE is present in the interior of the leased premises in any
      level that exceeds any governmental law, rule or regulation as a result of
      LESSEE's use of the leased premises. Said consultant shall also state
      that, after reasonable investigation, there is no contamination resulting
      from LESSEE's use of the leased premises which renders the leased premises
      unsuitable for future use and occupation by others. LESSEE shall provide
      LESSOR with a copy of said consultant's report. Time is of the essence.

H.    Prior to the termination date of this lease, LESSEE may remove equipment
      and furniture listed on the attached Exhibit A which have been installed
      by LESSEE if LESSEE has satisfactorily complied with all other conditions
      of this lease and if LESSEE repairs any and all damage resulting from such
      removal and restores the leased premises to their condition prior to the
      installation of said equipment, all on a timely basis prior to the end of
      the lease term. Time is of the essence.

LESSOR:  CUMMINGS PROPERTIES MANAGEMENT, INC.      LESSEE:  ANIKA RESEARCH, INC.

By: /s/ JAMES MCKEOWN                              By: /s/ SEAN MORAN
    -----------------                                  --------------
    President                                      Sean Moran
                                                   Chief Financial Officer

DATE: March 10, 1995

                                       11

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