Document:

<PAGE>

                                                                Exhibit 10.18(b)

                            SECOND AMENDMENT OF LEASE
                  (PARTIAL TERMINATION AND SURRENDER AGREEMENT)

     THIS AGREEMENT (this "Agreement") is made as of the 31st day of March, 2000
                           ---------
between EASTVIEW HOLDINGS LLC ("Landlord"), a Delaware limited liability
                                --------
company, having an address at c/o LCOR Asset Management L.P., One Penn Plaza,
Suite 3310, New York, New York 10119, and EMISPHERE TECHNOLOGIES, INC.
("Tenant"), a Delaware corporation, having an address at 765 Old Saw Mill River
  ------
Road, Tarrytown, New York 10591.

                              W I T N E S S E T H :
                              - - - - - - - - - -

     WHEREAS, Landlord's predecessor-in-interest and Tenant entered into a Lease
dated as of March 31, 1997 (the "Original Lease"), for certain premises shown on
                                 --------------
Exhibit A of the Original Lease (the "Original Premises") in the Linde Building
                                      -----------------
(765 Old Saw Mill River Road) (the "Linde Building") and the Spine Building (777
                                    --------------
Old Saw Mill River Road) (the "Spine Building") located within the project known
                               --------------
as The Landmark at Eastview, in the Towns of Mt. Pleasant and Greenburgh, New
York, as the Original Lease was amended by the Amendment of Lease dated as of
January 31, 1999 (the "First Amendment") (as amended, the "Lease");
                       ---------------                     -----

     WHEREAS, the First Amendment of Lease added approximately 2359 rentable
square feet of space in the mezzanine level of the Linde Building (the

"Mezzanine Space") to the Original Premises; and
 ---------------

     WHEREAS, Tenant wishes to surrender, and to be released from certain of its
obligations under the Lease with respect to, the entire Mezzanine Space (the

"Surrender Space", which Surrender Space is more particularly shown hatched on
 ---------------
Schedule A attached to this Agreement), and Landlord is willing to grant such
--------
release and accept such surrender of the Surrender Space, upon the terms and
conditions set forth in this Agreement.

     NOW, THEREFORE, in consideration of the mutual covenants herein contained
and for other good and valuable consideration, the mutual receipt and legal
sufficiency of which are hereby acknowledged, Landlord and Tenant agree as
follows:

     1. All capitalized terms not otherwise defined in this Agreement shall have
the meanings ascribed to them in the Lease.
<PAGE>

     2.  On or before December 31, 2000 (the "Surrender Date") Tenant shall
                                              --------------
vacate and surrender possession of the Surrender Space to Landlord and shall
surrender all of Tenant's right, title and interest in and to the Surrender
Space under the Lease, with the intent and purpose that the Term of the Lease
with respect to the Surrender Space shall be extinguished in the same manner and
with the same effect as if the Term of the Lease had expired on the Surrender
Date.

     3. Tenant shall pay all Fixed Rent and Additional Charges accruing under
the Lease with respect to the Surrender Space through and including the
Surrender Date in accordance with the Lease.

     4. On the Surrender Date, Tenant shall deliver the Surrender Space to
Landlord vacant, broom clean and free and clear of all tenancies, subtenancies
and occupancies, and otherwise in the condition in which the Premises are
required to be surrendered to Landlord under the terms of the Lease (as amended
by this Agreement) upon the expiration of the Term of the Lease, and otherwise
in accordance with the terms of the Lease (as amended by this Agreement),
including, without limitation, Articles 12 and 13 of the Lease.

     5. On the Surrender Date, Landlord shall accept the surrender of the
Surrender Space and release Tenant from its obligations under the Lease with
respect only to the Surrender Space, except that Tenant shall continue to remain
liable thereafter: (a) for Landlord's liabilities, costs and expenses of every
nature occasioned by Tenant's failure to surrender the Surrender Space to
Landlord in accordance with the terms of the Lease, as amended by this Agreement
(including, without limitation, reasonable attorneys' fees and disbursements and
reasonable attorneys' fees and disbursements incurred in establishing liability
under this Paragraph 5 and in collecting amounts payable hereunder); (b) for all
           -----------
liabilities and claims incurred by or made against Landlord and/or Tenant for
labor and materials asserted to have been furnished to Tenant or anyone claiming
by, through or under Tenant with respect to the Surrender Space, up to and
including the Surrender Date; (c) for any claims by Landlord against Tenant for
contribution or indemnification or both arising out of third-party claims
against Landlord to the extent provided for in the Lease, as amended by this
Agreement; (d) for all obligations and liabilities of Tenant with respect to the
Surrender Space accruing on or prior to the Surrender Date; and (e) for all
other obligations of Tenant with respect to the Surrender Space expressly
provided in the Lease to survive the termination or expiration of the Lease.
<PAGE>

     6. Effective on the Surrender Date, Tenant releases Landlord and its
successors and assigns from and against any and all claims, obligations and
liabilities of every kind or nature whatsoever thereafter arising out of or in
connection with the Surrender Space.

     7. Effective on the Surrender Date, the Lease shall be amended as follows
in order to reflect the Surrender of the Surrender Space: (a) "Tenant's
Proportionate Share" under the Lease shall mean 9.03% (subject to change as set
forth in Sections 4.01(c) and 4.06 of the Original Lease); (b) the "Fixed Rent"
as defined in Section 1.04 of the Original Lease shall be reduced by $23,590 per
annum, and effective September 1, 2003, the Fixed Rent, as decreased pursuant to
this sentence, shall be reduced by an additional $4,718 per annum. From and
after the Surrender Date, all references in the Lease to "Exhibit B" shall be
deemed to mean Exhibit B as modified by this Paragraph 7.

     8. Except as expressly set forth in this Agreement, nothing contained in
this Agreement shall affect Tenant's obligations and liabilities with respect to
the remainder of the Premises other than the Surrender Space demised to Tenant
under the Lease (the "Remaining Premises"), which obligations and liabilities
                      ------------------
shall continue under the Lease (as amended by this Agreement) as if this
Agreement had not been made. From and after the Surrender Date, the term
"Premises" under the Lease (and all references in the Lease thereto) shall be
deemed to mean only the Remaining Premises.

     9. Landlord shall have no obligation to perform any work in, or to
otherwise alter or improve the Remaining Premises (or to pay Tenant any sum
toward any such work, alterations or improvements), in order to separately
demise the Remaining Premises or otherwise, in connection with, or as a result
of, this Agreement.

     10. Tenant represents and warrants on behalf of itself and its successors
and assigns, that it has not done or suffered to be done (and Tenant agrees that
it will not do or suffer to be done) anything whereby the Surrender Space or any
alteration, decoration, installation or improvement in and to the Surrender
Space (collectively, the "Improvements") has or will become encumbered in any
                          ------------
way whatsoever and that no one other than Tenant has acquired or will acquire
through or under Tenant any right, title or interest in, to or under the
Surrender Space or the Improvements. This Paragraph 10 shall survive the
                                           ------------
termination or expiration of the Lease and this Agreement.

                                      -3-
<PAGE>

     11.  Simultaneously with the execution and delivery of this Agreement,
Landlord and Tenant shall execute a New York State Combined Real Estate Transfer
Tax Return and Credit Line Mortgage Certificate (the "TP-584").  Tenant shall
                                                      ------
file the TP-584 on or before the date required by law with the New York State
Department of Taxation and Finance and shall give Landlord written notice of
such filing. Although Landlord and Tenant do not anticipate that any New York
State Real Estate Transfer Tax ("State Transfer Tax") will be payable in
                                 ------------------
connection with this Agreement or the transaction contemplated hereby, to the
extent any State Transfer Tax is due and payable by Tenant as transferor, Tenant
shall pay same as and when due and shall also pay any and all late fees,
penalties and interest assessed for failure to pay same when due. Tenant shall
indemnify and hold harmless Landlord for, from and against any and all
liabilities, losses, claims, costs and expenses (including, without limitation,
reasonable attorneys' fees and disbursements and reasonable attorneys' fees and
disbursements incurred in establishing liability, and in collecting amounts
payable, under this Paragraph 11) arising from a breach of Tenant's obligations
                    ------------
under this Paragraph 11 or incurred in connection with any State Transfer Tax
           ------------
and/or any other real estate or real property transfer tax that is or may
become, or may be asserted to be or become, due, owing or imposed in connection
with this Agreement or the surrender of the Surrender Space now or hereafter by
the State of New York or any agent or instrumentality of such State, including,
without limitation, any late charges, penalties and interest imposed or to be
imposed in connection therewith. Tenant shall file such other returns,
affidavits and/or other documents, if any, that may be required in connection
with such other taxes and Landlord shall sign such returns, affidavits and
documents as required by law and otherwise cooperate with Tenant in making any
filing required in connection with such taxes. This Paragraph 11 shall survive
                                                     ------------
the termination or expiration of the Lease and this Agreement.

     12.  Landlord and Tenant each represents and warrants to the other that it
has not dealt with any broker in connection with this Agreement other than LCOR
Asset Management L.P. (the "Broker").  The execution and delivery of this
                            ------
Agreement by each party shall be conclusive evidence that such party
acknowledges that the other party has relied upon the foregoing representation
and warranty. Landlord and Tenant shall indemnify and hold harmless the other
from and against any and all claims for commission, fee or other compensation by
any person (other than the Broker with respect to Tenant's indemnity to
Landlord), who claims to have dealt with such party in connection with this
Agreement and for any and all costs incurred by the indemnified

                                      -4-
<PAGE>

party in connection with such claims, including, without limitation, reasonable
attorneys' fees and disbursements. This Paragraph 12 shall survive the
expiration or earlier termination of the Lease or this Agreement.

     13. This Agreement shall not be binding upon or enforceable against
Landlord or Tenant unless and until Landlord and Tenant shall have each executed
and unconditionally delivered to the other an executed counterpart of this
Agreement.

     14. This Agreement may be executed in several counterparts, each of which
shall be an original and all of which shall constitute but one and the same
instrument.

     15. This Agreement shall be governed by, and construed and interpreted in
accordance with, New York law, without regard to conflicts of law principles.

     16.  Except as amended by this Agreement, the Lease is ratified and
confirmed and remains in full force and effect.

     IN WITNESS WHEREOF, Landlord and Tenant have duly executed this Agreement
as of the day and year first written above.

                                     LANDLORD:

                                     EASTVIEW HOLDINGS LLC

                                     By:  EASTVIEW SPE INC.,
                                          its managing member

                                          By:______________________
                                              Name:
                                              Title:

                                     TENANT:

                                     EMISPHERE TECHNOLOGIES, INC.

                                     By:___________________________
                                         Name:
                                         Title:

                                      -5-
<PAGE>

STATE OF NEW YORK  )
                   ) ss.:
COUNTY OF NEW YORK )

     On the ______ day of _____ in the year 2000 before me, the undersigned,
personally appeared _______________________, personally known to me or proved to
me on the basis of satisfactory evidence to be the individual(s) whose name(s)
is (are) subscribed to the within instrument and acknowledged to me that
he/she/they executed the same in his/her/their capacity (ies), and that by
his/her/their signature(s) on the instrument, the individual(s), or the person
upon behalf of which the individual(s) acted, executed the instrument.

                                         -------------------------
                                         Notary Public

STATE OF NEW YORK  )
                   ) ss.:
COUNTY OF NEW YORK )

     On the ______ day of _____ in the year 2000 before me, the undersigned,
personally appeared _______________________, personally known to me or proved to
me on the basis of satisfactory evidence to be the individual(s) whose name(s)
is (are) subscribed to the within instrument and acknowledged to me that
he/she/they executed the same in his/her/their capacity (ies), and that by
his/her/their signature(s) on the instrument, the individual(s), or the person
upon behalf of which the individual(s) acted, executed the instrument.

                                         -------------------------
                                         Notary Public

                                      -6-
<PAGE>

                                   SCHEDULE A
                                   ----------

                                 Surrender Space
                                 ---------------

                                      A-1<PAGE>

                                                                Exhibit 10.18(c)

                            THIRD AMENDMENT OF LEASE

     THIS AGREEMENT dated as of March 31, 2000, between EASTVIEW HOLDING, LLC, a
Delaware limited liability company, having an address at c/o LCOR Asset
Management, L.P., One Penn Plaza, Suite 3310, New York, New York 10119
("Landlord"), and EMISPHERE TECHNOLOGIES, INC., a Delaware corporation, having
----------
an address at 765 Old Saw Mill River Road, Tarrytown, New York 10591 ("Tenant").
                                                                       ------

                                 W I T N E S S E T H:

     WHEREAS, Landlord's predecessor-in-interest and Tenant entered into a Lease
dated as of March 31, 1997 (the "Original Lease"), for certain premises shown on
                                 --------------
Exhibit A of the Original Lease (the "Original Premises") in the Linde Building
                                      -----------------
(765 Old Saw Mill River Road) (the "Linde Building") and the Spine Building (777
                                    --------------
Old Saw Mill River Road) (the "Spine Building") located within the project known
                               --------------
as The Landmark at Eastview, in the Towns of Mt. Pleasant and Greenburgh, New
York, as the Original Lease was amended by the Amendment of Lease dated as of
January 31, 1999 (the "First Amendment"), and as further amended by the Second
                       ---------------
Amendment of Lease (Partial Termination and Surrender Agreement) dated as of the
date hereof (the "Second Amendment") ( as amended, the "Lease");
                  ----------------                      -----

     WHEREAS, the First Amendment of Lease added approximately 2359 rentable
square feet of space in the mezzanine level of the Linde Building (the
"Mezzanine Space") to the Original Premises;
----------------

     WHEREAS, the Second Amendment of Lease will terminate the Lease with
respect to the entire Mezzanine Space as of the date upon which Tenant vacates
and surrenders the Mezzanine Space in the condition required under the Second
Amendment and in accordance with the other terms of the Second Amendment, which
date Tenant agrees shall not be later than December 31, 2000;

     WHEREAS, Landlord and Tenant desire to amend the Lease to add the following
additional premises to the Original Premises and otherwise amend the Lease, all
on the terms and conditions provided in this Agreement:

          (i)  approximately 17,045 rentable square feet of space on the second
     floor of the Linde Building substantially as shown hatched on the floor
     plan annexed hereto as Schedule A-1 (the "Additional Premises No. 1");
                            ------------       -------------------------

          (ii)  approximately 13,912 rentable square feet of space on the G
     level of the Spine Building substantially as shown hatched on the floor
     plan annexed hereto as Schedule A-2 (the "Additional Premises No. 2");
                            ------------       -------------------------

          (iii)  approximately 2,056 rentable square feet of space on the G
     level of the Spine Building substantially as shown hatched on the floor
     plan annexed hereto as Schedule A-3 (the "Additional Premises No. 3"); and
                            ------------       -------------------------

          (iv)  approximately 7,888 rentable square feet of space on the G level
     of the Spine Building substantially as shown hatched on the floor plan
     annexed hereto as Schedule A-4 (the "Additional Premises No. 4");
                       ------------       -------------------------
<PAGE>

     (Additional Premises No. 1, Additional Premises No. 2, Additional Premises
     No. 3, and Additional Premises No. 4 are hereinafter collectively referred
     to as, the "Additional Premises").
                 -------------------

     NOW, THEREFORE, in consideration of the mutual covenants contained in this
Agreement, Landlord and Tenant agree as follows:

     1.  Capitalized Terms.  All capitalized terms used in this Agreement which
         -----------------
are not otherwise defined herein shall have the meanings ascribed to them in the
Lease.

     2.  Commencement Dates for the Additional Premises.
         ----------------------------------------------

          (i)  The Additional Premises No. 1 is hereby added to, and shall be
considered a part of, the Original Premises effective on January 1, 2001 or the
date Tenant or any person claiming under or through Tenant first occupies the
Additional Premises No. 1 for the conduct of its business, whichever occurs
earlier (the "Additional Premises No. 1 Commencement Date").
              -------------------------------------------

          (ii)  The Additional Premises No. 2 is hereby added to, and shall be
considered a part of, the Original Premises effective on October 15, 2000 or the
date Tenant or any person claiming under or through Tenant first occupies the
Additional Premises No. 2 for the conduct of its business, whichever occurs
earlier (the "Additional Premises No. 2 Commencement Date").
              -------------------------------------------

          (iii)  The Additional Premises No. 3 is hereby added to, and shall be
considered a part of, the Original Premises effective on January 1, 2001 or the
date Tenant or any person claiming under or through Tenant first occupies the
Additional Premises No. 3 for the conduct of its business, whichever occurs
earlier (the "Additional Premises No. 3 Commencement Date").
              -------------------------------------------

          (iv)  The Additional Premises No. 4 is hereby added to, and shall be
considered a part of, the Original Premises effective on May 1, 2001 or the date
Tenant or any person claiming under or through Tenant first occupies the
Additional Premises No. 4 for the conduct of its business, whichever occurs
earlier (the "Additional Premises No. 4 Commencement Date").
              -------------------------------------------
The commencement dates for Additional Premises No. 1, Additional Premises No. 2,
Additional Premises No. 3, and Additional Premises No. 4 are hereinafter
collectively referred to as, the respective "Commencement Dates").
                                             ------------------

     The leasing of the Additional Premises shall be upon all of the terms,
conditions and provisions of the Lease, except as otherwise provided in this
Agreement.  After the respective Commencement Dates, all references in the Lease
to the "Premises" or the "demised premises" shall be deemed to include the
Additional Premises (or the portion thereof for which the commencement date has
occurred), unless the context requires otherwise and except as otherwise
provided in this Agreement.  Landlord and Tenant confirm that the Expiration
Date under the Lease is August 31, 2007 (subject to Tenant's options to extend
the Lease under Article 42 of the Lease).

     3.  Condition of Additional Premises.  Tenant shall accept possession of
         --------------------------------
the Additional Premises in "as is" condition on the respective Commencement
Dates and Landlord shall have no obligation to perform any work or make any
installations in order to prepare the Additional

                                      -2-
<PAGE>

Premises for Tenant's occupancy. The taking of occupancy of the whole or any
part of the Additional Premises by Tenant shall be conclusive evidence, as
against Tenant, that Tenant accepts possession of the same and that the
Additional Premises and the Building were in good and satisfactory condition at
the time such occupancy was so taken and that the Additional Premises were
substantially as shown on Schedules A-1, A-2, A-3 and A-4.
                          --------------------------------

     4.  License Period.  Landlord shall permit Tenant and Tenant's contractors
         --------------
to enter the Additional Premises during the period from and after (i) the date
hereof (with respect to the Additional Premises No. 1, the Additional Premises
No. 2 and the Additional Premises No. 3) and (ii) August 15, 2000 (with respect
to the Additional Premises No. 4) until the respective Commencement Dates (the
"License Periods"), for purposes of taking measurements and, after Landlord
----------------
shall have approved Tenant's plans and specifications therefor, to perform the
Alterations necessary to prepare the Additional Premises for Tenant's initial
occupancy in conformance with Article 12 of the Lease (collectively "Tenant's
                                                                     --------
Initial Alterations").  Landlord's review of the plans shall be done in
-------------------
accordance with Article 12 of the Lease, except, for purposes of this Agreement
only, (a) Tenant shall not be required to pay for Landlord's costs or expenses
to review Tenant's plans and (b) Landlord shall complete its review of Tenant's
plans (or any revision thereof) within five Business Days after the date such
plans were delivered to Landlord.   Notwithstanding the foregoing in this
Paragraph 4, Tenant shall have the right to access the Additional Premises No. 4
during Business Hours after the date hereof for purposes of taking measurements
only, provided Tenant shall have given reasonable advance notice to Landlord and
the tenant occupying such space (which notice  may be verbal).  During the
respective License Periods, Tenant shall, in addition to such other requirements
as are set forth in this Paragraph 4, comply, and cause any and all of its
                         -----------
agents, contractors, employees or invitees (collectively, "Persons Within
                                                           --------------
Tenant's Control") to comply with all of the other terms, covenants and
----------------
obligations on the part of Tenant to be kept, observed and performed pursuant to
the Lease, as amended by this Agreement, except that Tenant shall not be
required to pay with respect to the Additional Premises only, Fixed Rent, the
Tax Payment or the Operating Payment during the respective License Periods.
Prior to any entry permitted under this  Paragraph 4 (an "Early Entry"), Tenant
                                         -----------      -----------
shall provide Landlord with such proof as Landlord may reasonably require that
all persons entering upon the Additional Premises are covered by the insurance
required under Article 10 of the Original Lease.  Tenant shall be liable for any
and all damages and liability resulting from any Early Entry, and, as an express
condition of any Early Entry, Tenant shall indemnify and hold Landlord harmless
from and against any and all claims, liability, cost and expense (including,
without limitation, reasonable attorneys' fees and disbursements) arising from
or in connection with any Early Entry by Tenant or Persons Within Tenant's
Control in the Additional Premises.  During the respective License Periods,
Tenant shall pay Landlord's charges for such items for which Tenant is
separately billed under the Lease, including, without limitation, HVAC Electric
and Basic Electric used within the Additional Premises, and extra cleaning
services required as a result of Tenant's Initial Alterations. Such charges and
items shall be payable to Landlord within thirty (30) days after demand.  In
addition to the foregoing payments, commencing on January 1, 2001 and ending on
the Additional Premises No. 4 Commencement Date, Tenant shall pay to Landlord,
as an Additional Charge, $2,000 per month for maintenance and engineering work
performed by Landlord.  Upon completion of the Tenant's Initial Alterations (or
any phase thereof) Tenant shall deliver "as built" plans to Landlord.  In the
event Tenant does not obtain final "as built" plans, Tenant shall deliver to
Landlord a copy of Tenant's contractor's final marked plans.

                                      -3-
<PAGE>

     5.  Landlord's Contribution for the Additional Premises No. 1.  In
         ---------------------------------------------------------
consideration of Tenant's acceptance of the Additional Premises No. 1 "as is",
and of Tenant's performance of the Tenant's Initial Alterations with respect
thereto in conformance with the terms of the Lease and Paragraph 4 above,
                                                       -----------
Landlord shall pay up to but not in excess of an amount equal to $337,368
("Landlord's Contribution") for Tenant's actual costs of performing or
-------------------------
installing the Tenant's Initial Alterations to the Additional Premises No. 1.
For purposes of the preceding sentence, actual costs of performing or installing
Tenant's Initial Alterations shall include all so-called "hard" construction
costs and "soft" construction costs, such as costs and fees for design and
engineering and Tenant's professional and construction consultants ("Soft
                                                                     ----
Costs").  Tenant shall submit to Landlord a line item budget setting forth
estimated construction costs and Soft Costs prior to commencement of the
Tenant's Initial Alterations.  Provided that there shall not then be existing a
Tenant default beyond any notice and grace period provided under the Lease,
Landlord shall pay for such costs by paying the contractors, suppliers or
consultants designated by Tenant or by reimbursing Tenant (at Tenant's option)
from time to time during the progress of the Tenant's Initial Alterations (but
not more than once per month) within 30 days after receipt from Tenant of (i)
supporting documentation therefor approved by Tenant, accompanied by a
certification of the architect supervising the work (for work covered by such
architect's design), stating that the portion of the work for which Tenant is
applying for payment has been completed substantially in accordance with the
plans and specifications approved by Landlord, (ii) itemized bills for labor and
materials constituting portions of the Tenant's Initial Alterations submitted by
the contractors, suppliers or consultants of the services or materials rendered
(and where Tenant elects to be reimbursed, such bills shall have been marked
"paid" by the contractor, supplier or consultant) and (iii) waivers of liens
evidencing the payment for any prior work performed and materials supplied for
which Tenant previously applied for payment, executed and acknowledged by the
contractors, suppliers and consultants which are entitled by statute to file
mechanics liens..  Notwithstanding anything to the contrary contained in this
Paragraph 5, if, at the time Landlord's Contribution is required to be made,
-----------
Tenant is in arrears in the payment of Fixed Rent or Additional Charges, then
Landlord may offset the amount of such arrearages against the payment due from
Landlord under this Paragraph 5.
                    -----------

     6.  Fixed Rent.
         ----------

          (a)  Additional Premises No. 1.  Effective on the Additional Premises
               -------------------------
No. 1 Commencement Date, the Fixed Rent under the Lease shall be increased by
the following sums on account of the Additional Premises No. 1:

               (i)  $351,836.00 per annum ($29,319.67 per month) from the
                    Additional Premises No. 1 Commencement Date through the day
                    preceding the fifth anniversary of the Commencement Date;
                    and

               (ii) $359,554.00 per annum ($29,962.83 per month) from the fifth
                    anniversary of the Commencement Date through the Expiration
                    Date.

          (b)  Additional Premises No. 2.  Effective on the Additional Premises
               -------------------------
No. 2 Commencement Date, the Fixed Rent under the Lease shall be increased by
$319,976.00 per

                                      -4-
<PAGE>

annum ($26,664.67 per month) on account of the Additional Premises No. 2.

          (c)  Additional Premises No. 3.  Effective on the Additional Premises
               -------------------------
No. 3 Commencement Date, the Fixed Rent under the Lease shall be increased by
$45,232.00 per annum ($3,769.33 per month) on account of the Additional Premises
No. 3.

          (d)  Additional Premises No. 4.  Effective on the Additional Premises
               -------------------------
No. 4 Commencement Date, the Fixed Rent under the Lease shall be increased by
$173,954.00 per annum ($14,461.33 per month) on account of the Additional
Premises No. 4.

          (e)  Fixed Rent for a partial month shall be prorated on a per diem
basis.

          (f)   Notwithstanding anything to the contrary in the Lease, with
respect to the entire Premises, Tenant shall pay to Landlord (i) all Fixed Rent
in equal monthly installments in advance on the first day of each and every
calendar month during the term of the Lease and (ii) Additional Charges in
lawful money of the United States of America, without notice or demand, either
by (A) good and sufficient check drawn to Landlord's order on a bank or trust
company with an office in the State of New York, at Eastview Holdings LLC, c/o
First Union National Bank, P.O. Box 8500-4985, Philadelphia, Pennsylvania,
19178-4985, or (B) wire transfer to the following account: First Union National
Bank, ABA No. 031-201-467, Account No. 2000003297504 for credit to CDC Mortgage
Capital Inc., as Mortgagee of Eastview Holdings LLC, or at such other place, or
to Landlord's agent and at such other place, as Landlord may designate from time
to time.

     7.  Tenant's Proportionate Share.
         ----------------------------

          (a)  Additional Premises No. 1.  Effective on the Additional Premises
               -------------------------
No. 1 Commencement Date, Tenant's Proportionate Share shall be increased on
account of the Additional Premises No. 1 by an amount equal to 2.31%.

          (b)  Additional Premises No. 2.  Effective on the Additional Premises
               -------------------------
No. 2 Commencement Date, Tenant's Proportionate Share shall be increased on
account of the Additional Premises No. 2 by an amount equal to 1.88%.

          (c)  Additional Premises No. 3.  Effective on the Additional Premises
               -------------------------
No. 3 Commencement Date, Tenant's Proportionate Share shall be increased on
account of the Additional Premises No. 3 by an amount equal to .28%.

          (d)  Additional Premises No. 4.  Effective on the Additional Premises
               -------------------------
No. 4 Commencement Date, Tenant's Proportionate Share shall be increased on
account of the Additional Premises No. 4 by an amount equal to 1.07%.

     After the occurrence of all of the respective Commencement Dates,  Tenant's
Proportionate Share as defined in Section 4.01 (c) of the Original Lease shall
mean an amount equal to 14.57%.  Until such time, Tenant's Proportionate Share
shall increase as set forth above as the respective Commencement Dates occur.

                                      -5-
<PAGE>

     8.  Broker.  Landlord and Tenant each represents and warrants to the other
         ------
that it has not dealt with any broker in connection with this Agreement other
than LCOR Asset Management L.P. (the "Broker").  The execution and delivery of
                                      ------
this Agreement by each party shall be conclusive evidence that such party
acknowledges that the other party has relied upon the foregoing representation
and warranty.  Landlord and Tenant shall indemnify and hold harmless the other
from and against any and all claims for commission, fee or other compensation by
any person (other than the Broker with respect to Tenant's indemnity to
Landlord), who claims to have dealt with such party in connection with this
Agreement and the leasing of the Additional Premises and for any and all costs
incurred by the indemnified party in connection with such claims, including,
without limitation, reasonable attorneys' fees and disbursements.  This
provision shall survive the expiration or earlier termination of the Lease or
this Agreement.

     9.  Parking.
         -------

          (a)  Additional Premises No. 1.  Effective on the Additional Premises
               -------------------------
No. 1 Commencement Date, the number of parking spaces Tenant may use on a non-
exclusive basis as set forth in Section 35.01 and Exhibit D of the Original
Lease shall be increased by 40.

          (b)  Additional Premises No. 2.  Effective on the Additional Premises
               -------------------------
No. 2 Commencement Date, the number of parking spaces Tenant may use on a non-
exclusive basis as set forth in Section 35.01 and Exhibit D of the Original
Lease shall be increased by 60.

          (c)  Additional Premises No. 3.  Effective on the Additional Premises
               -------------------------
No. 3 Commencement Date, the number of parking spaces Tenant may use on a non-
exclusive basis as set forth in Section 35.01 and Exhibit D of the Original
Lease shall be increased by 4.

          (d)  Additional Premises No. 4.  Effective on the Additional Premises
               -------------------------
No. 4 Commencement Date, the number of parking spaces Tenant may use on a non-
exclusive basis as set forth in Section 35.01 and Exhibit D of the Original
Lease shall be increased by 16.

     After the occurrence of all of the respective Commencement Dates, the total
number of parking space Tenant may use on a non-exclusive basis as set forth in
Section 35.01 and    Exhibit D of the Original Lease shall be 320.  Until such
time, the total number of parking spaces Tenant may use shall increase as set
forth above as the respective Commencement Dates occur.

     10.  Inapplicable Provisions.  The following provisions in the Original
          -----------------------
Lease shall be inapplicable to the Additional Premise:
     - 1.04(b) (Fixed Rent Abatement);
     - 1.10(k) (Rent Commencement Date);
     - 4.01(c) (only references to "Applicable Abatement Factor");
     - 4.01(d) and (e) (Abatement);
     - Article 30 (Broker);
     - Article 38 (prior mortgagee approval); and
     - Exhibit K (equipment to be supplied by Landlord).

     11.  Modification of HVAC Electric. Notwithstanding anything to the
          -----------------------------
contrary in Section

                                      -6-
<PAGE>

16.01 and Exhibit E of the Original Lease, the amount of the Additional Charges
for HVAC Electric supplied to the Premises (including the Additional Premises)
shall be determined based upon Landlord's established mathematical model as
described in Schedule B annexed to this Agreement.
             ----------

     12.  In accordance with Article 31 of the Original Lease, Landlord and
Tenant hereby designate the follow addresses for all notice, consent, approval
or other communication required or permitted  under the lease:

          if to Tenant at Tenant's address set forth on the first page of this
     Agreement or at any place where Tenant or any agent or employee of Tenant
     may be found if given subsequent to Tenant's vacating, deserting,
     abandoning or surrendering the Premises, or

          if to Landlord, at Landlord's address set forth on the first page of
     this Agreement, Attn: Director of Property Management, and with a copy to
     (i) LCOR Asset Management L.P., 777 Old Saw Mill River Road, Tarrytown, New
     York 10591, Attention: Management Office and (ii) any mortgagee or superior
     lessor who may have requested the same, by notice given in accordance with
     Article 31 of the Original Lease (as amended by this Paragraph 12) at the
                                                          ------------
     address designated by such mortgagee or superior lessor.

     13.  Rent Cap for First Extension Term.  Section 42.01 of the Lease is
          ---------------------------------
hereby amended as follows: in the event Tenant exercises the First Extension
Option, the Fixed Rent payable by Tenant to Landlord during the First Extension
Term shall be at an annual rate equal to the lesser of (a) 95% of the Fair
Market Rental for the Premises, determined in accordance with Section 42.04 and
(b) $32 multiplied by the number of rentable square feet in the Premises.

     14.  No Oral Modification.  This Agreement may not be changed or terminated
          --------------------
orally, but only by an agreement in writing signed by Landlord and Tenant.

     15.  No Offer.  This Agreement is offered for signature by Tenant and it is
          --------
understood that this Agreement shall not be binding upon Landlord unless and
until Landlord shall have executed and delivered a fully executed copy of this
Agreement to Tenant.

     16.   Ratification.  Except as modified by this Agreement, the provisions
           ------------
of the Lease are confirmed and approved and shall continue in full force and
effect.

                                      -7-
<PAGE>

     IN WITNESS WHEREOF, Landlord and Tenant have executed this Agreement as of
the day and year first above written.

                         EASTVIEW HOLDINGS LLC, Landlord

                         By:  EASTVIEW SPE INC., its Managing Member

                         By:________________________________________
                            Name:
                            Title:

                         EMISPHERE TECHNOLOGIES, INC., Tenant

                         By:________________________________________
                            Name:
                            Title:

                                      -8-
<PAGE>

                                  SCHEDULE A-1

                            ADDITIONAL PREMISES NO. 1
                            -------------------------

<PAGE>

                                  SCHEDULE A-2

                            ADDITIONAL PREMISES NO. 2
                            -------------------------
<PAGE>

                                 SCHEDULE A-3

                            ADDITIONAL PREMISES NO. 3
                            -------------------------
<PAGE>

                                  SCHEDULE A-4

                            ADDITIONAL PREMISES NO. 4
                            -------------------------
<PAGE>

                                   SCHEDULE B

                                   HVAC MODEL
                                   ----------

Monthly HVAC (Heating, Ventilation and Air Conditioning) billings for each
tenant are calculated by multiplying the monthly airflow in million cubic feet
(MCF) for each tenant by the cost per MCF, also calculated monthly.

The monthly air flow for each tenant is determined by multiplying the full-load
airflow rating of each fan feeding the tenant space in cubic feet per minute
(CFM) by the runtime factor provided on the fan schedule and by 60 to provide an
hourly usage in cubic feet. This is done each hour, and summed for the month to
provide a total airflow for the month, expressed in MCF.

The runtime factor for each fan is provided on a fan schedule, and accounts for
both partial runtime during an hour, and reduced flow on setback. Any changes to
the fan schedule for billing purposes must be requested by the tenant in writing
at least five (5) working days before the change is to take place.

Airflow from a fan providing air to more than one tenant will be allocated based
on the percentage of MCF delivered.

The cost per MCF is determined by taking the appropriate costs associated with
supplying and delivering conditioned air to tenant space and dividing it by the
total airflow provided to the site, calculated as above and summing across all
fans. This cost is calculated monthly.

                                      B-0

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