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                                                                    Exhibit 10.8

                               SUBLEASE AGREEMENT

This Sublease Agreement (this "Sublease") dated March 1, 1999, for reference
purposes only, is entered into by and between METAXEN LLC, a Delaware limited
liability company ("Sublessor") and EXELIXIS PHARMACEUTICALS, INC., a Delaware
corporation ("Sublessee"), and is subject to the terms and conditions of that
certain Build-To-Suit Lease ("Master Lease") dated May 27, 1997 (as amended by
that certain First Amendment to Lease dated as of April 13, 1998 (the "First
Amendment")) entered into by BRITANNIA POINTE GRAND LIMITED PARTNERSHIP, a
California limited partnership ("Master Lessor"), as Landlord, and Sublessor as
Tenant. A copy of the Master Lease is attached hereto as Exhibit "A".

         1.       Premises. Sublessor hereby leases to Sublessee, and Sublessee
hereby hires from Sublessor, on and subject to the terms and conditions
hereinafter set forth, the following premises (the "Sublease Premises"),
situated in the City of South San Francisco, County of San Mateo, State of
California, commonly known as a portion of the ground floor of Building H (the
"Building") in the Britannia Pointe Grand Business Park (the "Center") and
consisting of the following: (i) approximately three thousand forty (3,040)
leasable square feet backward lined in Exhibit "B", attached hereto, and
incorporated herein by this reference (the "Ground Floor Leased Area"); (ii)
approximately fifty percent (50%) of four thousand nine hundred sixty eight
(4,968) leasable square feet dotted in the above referenced Exhibit B (the
"Ground Floor Shared Area"); (iii) approximately three thousand nineteen (3,019)
leasable square feet backward lined in Exhibit "B-1", attached hereto and
incorporated herein by this reference (the "Second Floor Leased Area"); and (iv)
approximately twenty five percent (25%) of five thousand six hundred seventy
seven (5,677) leasable square feet forward dotted in the above referenced
Exhibit B-1 (the "Second Floor Shared Area"). The Sublease Premises include the
laboratory benches, water systems, fume hoods, laminar flow hoods and other
laboratory support space as specified in Exhibit "B-2", attached hereto, and
incorporated herein by this reference. Sublessee shall have the right to use the
Common Areas as described in the Master Lease, subject to the rights of Master
Lessor, Sublessor and other tenants of the Center. The right of Sublessee to use
the Ground Floor Shared Area and the Second Floor Shared Area is non-exclusive
and shall be subject to reasonable rules and requirements of Sublessor.
Sublessor shall have the primary right to use both the Ground Floor Shared Area
and the Second Floor Shared Area. Sublessee shall have the right to use no more
than fifty percent (50%) of the Ground Floor Shared Area. Furthermore, Sublessee
shall have the right to use no more than twenty five percent (25%) the Second
Floor Shared Area.

         2.       Master Lease.

                  a.       Sublease is Subordinate to Master Lease. This
Sublease is subject and subordinate to the Master Lease. Sublessee shall not
commit or permit to be committed on the Sublease Premises any act or omission
which shall violate any terms or condition of the Master Lease. If the Master
Lease terminates, this Sublease shall terminate. Sublessor shall have no
liability to Sublessee, if the Master Lease terminates without fault of
Sublessor. Sublessor hereby represents and warrants to Sublessee that (i)
Sublessor knows of no claims or defenses or circumstances which, with the
passage of time, would lead to claims or defenses by Master

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Lessor against Sublessor as tenant under the Master Lease; (ii) this Sublease,
if consented to by Master Lessor as provided for herein, does not violate any
provision of the Master Lease, and (iii) no provision of this Sublease is in
violation of the terms of the Master Lease. Sublessor hereby covenants and
agrees that, without the prior written consent of Sublessee, which consent shall
not be unreasonably withheld or delayed, Sublessor shall not (i) terminate the
Master Lease, (ii) amend or otherwise modify the terms of the Master Lease,
unless such modification would apply only to a matter that would take effect
only after the Expiration Date (or earlier termination of this Sublease), or
(iii) willfully breach the terms of the Sublease or the Master Lease. Sublessor
hereby agrees to perform its obligations as tenant under the Master Lease if and
to the extent those obligations are not assumed by Sublessee pursuant to the
terms of this Sublease.

                  b.       Application of Master Lease Provisions. Except as
otherwise expressly provided in this Sublease, Sublessee shall assume and
perform, with respect to the Sublease Premises, the obligations of the Sublessor
as Lessee under the Master Lease arising after the date of this Sublease.
Therefore, except as otherwise provided, for the purpose of this Sublease;
wherever in the Master Lease "Landlord" is used, it shall be deemed to mean the
Sublessor herein, and wherever in the Master Lease "Tenant" is used, it shall be
deemed to mean the Sublessee herein, and wherever in the Master Lease "Lease" is
used, it shall be deemed to mean this Sublease.

                  c.       Incorporation of Master Lease Provisions.

                           (1)      All of the terms and conditions in the
Master Lease, as they relate to the Sublease Premises, are incorporated herein
except for: 1.1 (Premises); 1.2 (Landlord's Reserved Rights); Sections 1.3
(First Refusal); 2,1 (Term); 2.2 (Early Possession); 2.3 (Delay in Possession);
2.6 (Option to Extend); 3.1 (Minimum Rent); 4.1 (Stock Warrants); 6,2 (Real
Property Taxes); 7 (Operating Expenses); 8.1 (Payment of Utilities); Tenant's
obligation for HVAC repair and entry into a service contract under 10.2(a);
12.1(b); 19.1 (Notices), 19.11 (Financial Information); Financial Information);
19.15 (Brokers); 19.16 (Memorandum of Lease), Articles 4 (Stock Warrants), 5
(Construction) and Article 18 (Security Deposit), the First Amendment to Lease
as it pertains to warrants, and Exhibit C.

                           (2)      Except as otherwise provided herein,
Sublessor is responsible for all financial obligations under the Master Lease.

                           (3)      As between Sublessor and Sublessee only, it
is hereby agreed that any breach or default under that certain AGREEMENT BETWEEN
METAXEN AND EXELEXSIS REGARDING PROPRIETARY INFORMATION AND NON SOLICITATION
(the "Non-Solicitation Agreement") dated as of even date herewith shall
constitute an additional default under section 16.1 of the Master Lease and
shall not require any additional notice to either Sublessor or Sublessee except
as expressly provided in said Non-Solicitation Agreement. Any such breach or
default shall entitle the party to the remedies provided in the Master Lease, in
addition to the remedies provided in the Non-Solicitation Agreement.

                                       2

<PAGE>

                  d.       Indemnity. Except to the extent caused by Sublessor,
or Sublessor's agents', employees' or invitees' negligence or willful
misconduct, Sublessee shall indemnify and hold Sublessor harmless against and
from all liability, judgments, costs, damages, claims or demands, including
reasonable attorney's fees, arising out of Sublessee's failure to comply with or
perform Sublessee's obligations under this Sublease, including, but not limited
to, Sublessee's obligation to immediately disclose any violations of the
warranty as set forth in section 2.f, below. Except to the extent caused by
Sublessee, or Sublessee's agents', employees' or invitees' negligence or willful
misconduct, Sublessor shall indemnify and hold Sublessee harmless against and
from all liability, judgments, costs, damages, claims or demands, including
reasonable attorney's fees, arising out of Sublessor's failure to comply with or
perform Sublessor's obligations under this Sublease.

                  e.       Master Lease in Effect. Sublessor represents to
Sublessee that the Master Lease is in full force and effect and that, to
Sublessor's knowledge, no default exists on the part of any party to the Master
Lease; furthermore Sublessor represents and warrants that it has not received
any notification from Master Lessor of any default under the Master Lease or
notice of any potential default under the Master Lease. Subject to the terms and
provisions of this Sublease, Sublessor agrees to keep the Master Lease in full
force and effect during the term of this Sublease, subject, however, to any
earlier termination of the Master Lease without the default of Sublessor.

                  f.       Warranty. Section 6.2 of the Master Lease creates a
warranty in favor of Sublessor. Sublessee shall provide Sublessor with written
notification of any violation of the warranty in Section 6.2, promptly following
the discovery by Sublessee of such violation.

                  g.       To the extent that any financial terms contained in
this Sublease that are applicable to Sublessor and Sublessee only conflict with
similar provisions in the Master Lease, this Sublease shall prevail.

         3.       Sublease Term; Delivery of Possession.

                  a.       Term. The term of this Sublease shall begin on March
1, 1999 ("Commencement Date") and end no earlier than May 31,2000 and no later
than September 30 2000 ("Expiration Date") unless sooner terminated pursuant to
any provision hereof or of the Master Lease (the "Term"). Any extension beyond
the Expiration Date must be in a writing signed by both parties on or before one
hundred twenty (120) days prior to the Expiration Date. In no event shall the
term of this Sublease extend beyond the expiration of the Master Lease. The
actual Expiration Date shall be that date set forth in a written notice to
Sublessor delivered by Sublessee no earlier than May 1, 2000, and shall be
effective at the completion of the 30th day thereafter, so long as the actual
Expiration Date is no earlier than May 31, 2000 and no later than September 30,
2000.

                  b.       Delivery of Possession.

                           (1)      If Sublessee is to seek to have any
improvements performed in either the Ground Floor Leased Area or the Second
Floor Leased Areas (Sublessee shall have no

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right to modify or otherwise alter the Ground Floor Shared Area and/or the
Second Floor Shared Area) and if Sublessee shall fail to deliver to Sublessor a
schedule of improvements, along with plans and specifications thereto (including
projected costs) reasonably acceptable to Sublessor on or before sixty (60) days
following the execution of this Sublease, Sublessor, in its discretion, may
terminate its obligations under this Sublease at any time.

                           (2)      Sublessor will deliver the Sublease Premises
subject to all- applicable zoning, municipal, county and state laws, ordinances
and regulations governing and regulating the use of the Sublease Premises, and
Sublessee accepts the Sublease Premises subject thereto. Sublessee shall accept
the Sublease Premises in broom clean condition and otherwise "as is".
Notwithstanding the foregoing, Sublessor represents and warrants to Tenant that,
as of the Commencement Date, the Sublease Premises, including any improvements
made by Master Lessor shall be operational as designed and Building services
serving the Sublease Premises shall be operational as designed. If, during the
first sixty (60) days of the Term hereof, Sublessee notifies Sublessor of any
defects in the condition of the Sublease Premises, Sublessee shall have no
obligation to repair such defects upon the expiration or earlier termination of
this Sublease and Sublessor shall promptly notify Master Lessor, if it is the
responsibility of Master Lessor, or if the responsibility of Sublessor, shall
promptly commence the repair of any such defect. Sublessor shall assign its
rights or, alternatively, shall itself enforce such rights pursuant to any
manufacturer or other warranty covering the Sublease Premises.

                           (3)      Sublessor and Sublessee shall conduct a
walk-through inspection of the Sublease Premises prior to the Commencement Date,
and if the building systems in the Sublease Premises are found not to be in good
and working condition, a "punchlist" shall be developed identifying those areas
of repairs which are necessary to bring such building systems into good and
working condition and Sublessor shall immediately notify Master Lessor of the
need of such repairs, unless the repairs are the responsibility of Sublessor, in
which case Sublessor shall promptly commence such repair. Sublessor shall use
its reasonable efforts if necessary to compel Master Lessor to make such repairs
(if such repairs are the obligation of Master Lessor)

                  c.       Early Possession. In the event Sublessee, with
Sublessor's consent, takes possession of the Sublease Premises prior to the
Commencement Date, such occupancy shall be subject to all the provisions of this
Sublease, shall not advance the termination date of this Sublease, and Sublessee
shall pay Base Rent for the period prior to the Commencement Date at the Base
Rent prescribed for the initial month of the Sublease term, prorated at the rate
of l/30th thereof per day. If Sublessor consents to entry by Sublessee for the
purpose of installing furniture, equipment, telephone and computer systems, and
the like and/or for temporary staging or storage of Sublessee's property, such
entry shall not trigger an obligation to pay Base Rent prior to the
Commencement Date. It is contemplated that Sublessee shall have access to the
Premises on March 1, 1999, pursuant to the terms of this section relating to
early possession.

         4.       Rent. Sublessee shall pay to Sublessor no later than the first
day of each calendar month of the Term of this Sublease without deduction, set
off, prior notice or demand, as rent for the Sublease Premises, monthly rent
("Base Rent") as set forth in the rent schedule below, and

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subject to the terms and provisions of section 3.2 of the Master Lease. Base
Rent shall commence on March 1, 1999 (the "Rent Commencement Date").

                                 Rent Schedule

<TABLE>
<CAPTION>
Leased Premises             Base Rent/Month   Rent/Sq.ft/month  Approx. Sq. Feet
---------------             ---------------   ----------------  ----------------
<S>                         <C>               <C>               <C>
Ground Floor Leased Area      $ 5,472.00            $1.80          3,040
Ground Floor Shared Area(1)   $ 4,471.20            $1.80          2,484 (2)
Second Floor Leased Area      $10,566.50            $3.50          3,019
Second Floor Shared Area(3)   $ 4,967.38            $3.50          1,419.25 (4)
                              ----------

Total                         $25,477.00
</TABLE>

Sublessor and Sublessee each hereby acknowledge and agree that the parties
hereto intend this Sublease to be on a "full-service" basis and Sublessee shall
only be responsible to pay Base Rent and no other operating costs or service
expenses.

         5.       Security Deposit. Concurrently herewith, Sublessee shall
deposit Fifty Thousand Nine Hundred Fifty Four Dollars ($50,944.00) with
Sublessor as security for Sublessee's performance of its obligations under the
terms of this Sublease. Sublessor shall not be required to keep the any cash
portion of the Security Deposit separate from its general funds, or to pay any
interest thereon. The Security Deposit shall be held by Sublessor and may be
applied by Sublessor in accordance with the provisions of Article 18 of the
Master Lease.

         6.       Use.

                  a.       Permitted Use. The Sublease Premises shall be used
and occupied only for office, biotechnology/pharmaceutical research and
development, manufacturing, warehousing related to such uses, and other
permitted uses under the Master Lease. Sublessee shall use and occupy the
Sublease Premises in accordance with the Master Lease, including, but not
limited to Section 11.6, thereof.

                  b.       No Representations or Warranties. Sublessee
acknowledges that neither Sublessor nor Sublessor's agents have made any
representation or warranty as to the suitability of the Sublease Premises for
the conduct of Sublessee's business.

         7.       Operating Expenses. At no time prior to the Expiration Date,
is Sublessee required to pay as additional rent the amounts for which Sublessor
is liable to.Master Lessor pursuant to Article 7 (Operating Expenses) of the
Master Lease. In addition, until the Expiration

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

(1) Gross Ground Floor Shared Area equal to 4,968 square feet divided by 2, or
    2,484x1.80.

(2) See footnote 1, above.

(3) Gross Second Floor Shared Area equal to 5,677 square feet divided by 4, or
    1,419.25x3.50

(4) See footnote 3, above.

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Date, Sublessee shall have no liability for any utilities it consumes in the
Premises, The parties hereto hereby acknowledge that this Sublease is on a "full
service" basis and Sublessee shall not be responsible for any operating costs or
expenses, insurance or taxes.

         8.       Alterations. Notwithstanding the provisions of Article 9 of
the Master Lease, any alteration, which requires Master Lessor's approval
pursuant to the Master Lease, shall not be commenced by Sublessee unless and
until such consent is obtained. At the time Sublessor and Master Lessor consent
to any alteration, additions or improvements, Sublessor and Master Lessor shall
inform Sublessee in writing whether Sublessee is responsible for the removal of
such alterations and improvements at the expiration or earlier termination of
the term of this Sublease, provided that Sublessee, in its request for consent
to the alteration, addition, or improvement, has expressly requested that
Sublessor and Master Lessor specify the nature and extent of any such removal
obligation. If such notification is not made, Sublessee shall have no
responsibility to remove any such alteration or improvement at the expiration or
earlier termination of this Sublease. Any alteration made by Sublessee shall
become a part of the Sublease Premises, and at Sublessor's election (and to the
extent required, the consent of the Master Lessor), shall be surrendered to
Sublessor at the end of the Sublease term. Any alteration made by Sublessee
shall, at Sublessor's election become Sublessor's property throughout the
Sublease term except for any specialized improvements installed by Sublessee
(which improvements shall be part of Sublessee's Equipment and Alterations, as
defined in Exhibit B-2), which improvements shall remain the property of
Sublessee and which improvements shall be . removed by Sublessee at the
expiration or earlier termination hereof. In the event Sublessor is (or becomes)
obligated under the Master Lease to remove any of Sublessee's alterations,
Sublessee shall be obligated to remove same at Sublessee's sole cost and expense
and to restore the Sublease Premises to its condition prior to the alteration
but only to the extent required by Sublessor or Master Lessor in their written
consent to any such alteration. In the event that Sublessee removes any items it
is permitted to remove under Exhibit B-2, Sublessee, subject to the provisions
of the second sentence of this section 8, at its sole cost and expense, shall
restore the Sublease Premises to its condition prior to alteration.

         9.       Repairs. Pursuant to the Master Lease, Master Lessor is
responsible to repair and maintain the roof (structural portions only), exterior
walls and other structural portions of the Building and the Common Areas. As to
such matters, Sublessor's sole obligation to Sublessee shall be to request
performance of such obligations by Master Lessor. In the event Master Lessor
breaches its obligations, Sublessor will assign to Sublessee its right to
enforce such obligation and shall otherwise cooperate with Sublessee in
connection therewith, provided, however, Sublessee, at its sole cost and
expense, shall be responsible for enforcement thereof without reimbursement from
Sublessor. Sublessee, not Master Lessor, shall be responsible for the repair of
the roof and structural portions of the Building to the extent the need for
maintenance or repair is caused by the gross negligence or willful misconduct
of Sublessee, in which case Sublessee shall pay to Sublessor the cost of
(including reasonable overhead expense of Sublessor) the maintenance and repairs
caused by Sublessee (except (i) to the extent the damage is covered by any
insurance maintained by Master Lessor or Sublessor, or, (ii) if Master Lessor
fails to maintain the insurance required to be maintained by Master Lessor
pursuant to the terms of the Master Lease, to the extent the damage would have
been covered by insurance, if Master Lessor

                                       6

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had maintained the required insurance). There shall be no abatement of Base Rent
and no liability of Master Lessor or Sublessor by reason of any injury to or
interference with Sublessee's business arising from the making of any repairs,
alterations or improvements in or to the fixtures, appurtenances and equipment
therein, provided that Sublessor shall request Master Lessor to use reasonable
efforts to minimize the interruption of Sublessee's use and occupancy of the
Sublease Premises in connection with its performance of the repairs and
maintenance (although nothing contained herein shall be deemed to obligate
Master Lessor to pay any overtime costs in order to minimize such interference,
or otherwise to perform the repairs or maintenance during hours other than
normal business hours). As to all matters that neither Master Lessor nor
Sublessee is required to maintain or repair under the Master Lease or this
Sublease, as the case may be, Sublessor shall be responsible therefore, and
shall promptly and regularly maintain and repair the Sublease Premises.
Notwithstanding anything to foregoing, any damage caused by the negligence or
willful misconduct of Sublessee, shall promptly be repaired by Sublessee, at
Sublessee's own cost and expense, and in a manner reasonably acceptable to
Master Lessor and Sublessor.

         10.      Insurance.

                  a.       Sublessee shall maintain commercial general liability
insurance coverage as required by section 12. l(a) of the Master Lease (but
prorated based upon the Sublease Premises to the Premises under the Master
Lease) which has been incorporated into this Sublease by reference. Each policy
of insurance, which Sublessee is required to maintain pursuant to this Lease,
shall name both Sublessor and Master Lessor (as well as Master Lessor's general
partners and Managing Agent) as additional insureds (including cross-liability
endorsements). Sublessee's insurance coverage shall be primary and
non-contributory as respects any insurance maintained by Sublessor and/or Master
Lessor. Sublessee shall deliver evidence of the coverage required hereunder (i)
thirty (30) days prior to occupancy and (ii) within ten (10) days of the renewal
date for each policy of insurance required hereunder.

                  b.       Pursuant to the terms of the Master Lease as provided
in Section 12. l(b) thereof, Master Lessor is obligated to maintain certain
insurance coverage with respect to certain perils. Sublessor's sole obligation
to Sublessee with respect to Master Lessor's obligations pursuant to said
Section 12.1(b) shall be to request performance of such obligations by Master
Lessor. In the event Master Lessor breaches its obligations, Sublessor will
assign to Sublessee its right to enforce such obligation and shall otherwise
cooperate with Sublessee in connection therewith, provided, however, Sublessee,
at its sole cost and expense, shall be responsible for enforcement thereof
without reimbursement from Sublessor. In the event Sublessor cannot assign such
rights, Sublessor shall diligently enforce its rights as Tenant under the Master
Lease.

         11.      Damage or Destruction.

                  a.       Master Lessor Has Obligation to Restore. If the
Sublease Premises are damaged or destroyed, Master Lessor has the obligation
pursuant to Article 15 of the Master Lease to repair the Sublease Premises
unless Master Lessor has the right to terminate. If Master Lessor fails to
perform its obligations pursuant to Article 15 of the Master Lease, Sublessor's
sole obligation to Sublessee shall be to request performance of such obligations
by Master Lessor. In

                                       7

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the event Master Lessor breaches its obligations, Sublessor will assign to
Sublessee its right to enforce such obligation, provided, however, Sublessee, at
its sole cost and expense, shall be responsible for enforcement thereof without
reimbursement from Sublessor. In the event Sublessor cannot assign its rights,
Sublessor shall diligently enforce its rights under the Master Lease.

                  b.       Termination of Master Lease. If the Master Lease
terminates pursuant to Article 15 of the Master Lease, this Sublease shall
terminate concurrently with the termination of the Master Lease.

                  c.       Sublessee Notice; Right to Terminate. Within twenty
(20) days following written request from Sublessor, Sublessee shall give notice
to Sublessor in writing whether Sublessee agrees to continue this Sublease in
effect if Master Lessor reasonably determines that the repair of the Sublease
Premises or the Building cannot be completed within three hundred sixty five
(365) days after the casualty. If Sublessee does not so agree to continue this
Sublease in effect then this Sublease shall terminate. If Sublessee agrees to
continue this Sublease in effect as aforesaid, then Sublessor shall have no
right to exercise its right (if any) to terminate the Master Lease or this
Sublease. If (i) Master Lessor reasonably determines that the repair of the
Sublease Premises or the Building cannot be completed within three hundred sixty
five (365) days after the casualty, (ii) neither Master Lessor nor Sublessor
have elected to terminate the Master Lease, and (iii) Sublessee agrees to
continue this Sublease in effect notwithstanding the time to reconstruct, then
this Sublease shall continue in effect, and Sublessee shall fulfill all of the
obligations of Sublessor pursuant to the provisions of Article 15 of the Master
Lease, as it pertains to the Sublease Premises.

                  d.       Limited Obligation to Repair. Master Lessor's
obligation, should Master Lessor elect or be obligated to repair or rebuild,
shall be limited to the terms and conditions of the Master Lease. Master Lessor
shall have no obligation to replace or restore the Sublessee Equipment and
Alterations (as described in Exhibit B-2) or any other alterations installed by
Sublessor or Sublessee, unless specifically required by the Master Lease.

                  e.       Abatement of Rent. Rent under this Sublease shall
abate to the same extent as the Rent owing by Sublessor under the Master Lease
abates during any casualty repair period.

                  f.       Damage Near End of Term. In addition to the rights to
terminate specified in subsection 11. c of this Sublease, either Sublessor or
Sublessee shall have the right to cancel and terminate this Sublease as of the
date of the occurrence of destruction or damage if the Sublease Premises or the
Building is substantially destroyed or damaged (i.e., there is damage or
destruction which Sublessor reasonably determines would require more than sixty
(60) days to repair) and made untenantable during the last twelve (12) months of
the term of the Master Lease. Sublessor or Sublessee, as applicable, shall give
written notice of its election to terminate this Sublease under this subsection
f. within thirty (30) days after Master Lessor or Sublessor determines that the
damage or destruction would require more than sixty (60) days to repair. If
either Master Lessor or Sublessor elects to terminate the Master Lease pursuant
to Article 15 of

                                       8

<PAGE>

the Master Lease, this Sublease shall terminate concurrently with the
termination of the Master Lease. If neither Master Lessor nor Sublessor
terminates the Master Lease and if neither Sublessor nor Sublessee elects to
terminate this Sublease, the repair of the damage shall be governed by Article
15 of the Master Lease.

                  g.       Insurance Proceeds. If this Sublease is terminated,
Master Lessor and Sublessor may each keep all their respective insurance
proceeds resulting from the damage except for those proceeds, if any, which
specifically insured Sublessee's personal property and trade fixtures which
Sublessee has a right or obligation to remove upon the expiration of the
Sublease term. Sublessor shall be entitled to receive from Sublessee the
proceeds of insurance carried by Sublessee with respect to Sublessee
Improvements or other alterations installed in the Sublease Premises by
Sublessor or at Sublessor's expense. To the extent that Sublessee has paid for
any alterations regardless of whether the alterations may become the property of
Sublessor upon termination of this Sublease, Sublessee shall receive any portion
of the insurance proceeds payable with respect to the then unamortized cost
(based on a 2 year life of the alteration on a straight line amortization
schedule) for the applicable alterations, reduced by the amounts necessary to
pay off any equipment lease or other lien against the applicable alteration, and
the balance of the proceeds, if any, will be payable to Sublessor. With respect
to those Alterations, which Sublessee is obligated to remove at the end of the
Sublease term which are the property of Sublessee, all proceeds of any
insurance, carried by Sublessor or Sublessee shall be paid to Sublessee.

                  h.       Uninsured Casualty. If the Master Lease terminates
pursuant to the provisions of Article 15 of the Master Lease, this Sublease
shall terminate.

         12.      Eminent Domain. If all or any part of the Sublease Premises is
taken for public or quasi-public use by a governmental authority under the power
of eminent domain or is conveyed to a governmental authority in lieu of such
taking, and if the taking or conveyance causes the remaining part of the
Sublease Premises to be untenantable and inadequate for use by Sublessee for the
purpose for which they were leased, then Sublessee, at its option and by giving
notice within fifteen (15) days after the taking, may terminate this Sublease as
of the date Sublessee is required to surrender possession of the Sublease
Premises. If a part of the Sublease Premises is taken or conveyed but the
remaining part is tenantable and adequate for Sublessee's use in Sublessee's
reasonable determination, then this Sublease shall be terminated as to the part
taken or conveyed as of the date Sublessee surrenders possession. All
compensation awarded for the taking or conveyance shall be the property of
Master Lessor and Sublessor, as their interests may appear, and Sublessee hereby
assigns to Sublessor all its right, title and interest in and to the award,
unless the governmental authority makes only one (1) award, and the award
contains compensation for the value of moving expenses, Sublessee's personal
property, trade fixtures and alterations (including the Sublessee Improvements),
Sublessee's Equipment and Alterations, in which case, subject to the rights of
any mortgagee or beneficiary of a deed of trust holding a lien on the Property
and to Master Lessor's rights under the Master Lease, Sublessee shall be
entitled to the compensation paid for Sublessee's moving expenses, trade
fixtures, personal property, Sublessee's Equipment and Alterations, and the
portion of the award attributable to the then unamortized cost of alterations
and improvements constructed at Sublessee's expense (which are

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<PAGE>

to be amortized on a straight line basis over the initial term of this
Sublease). Sublessee shall have the right, however, to recover from the
governmental authority, but not from Sublessor or Master Lessor, except as
provided in the preceding sentence, such compensation as may be awarded to
Sublessee on account of the interruption of Sublessee's business, moving and
relocation expenses and removal of Sublessee's trade fixtures and personal
property.

         13.      Assignment and Subletting. Notwithstanding any provision of
this Sublease to the contrary, if Sublessor consents to a sublet, Sublessee
shall pay to Sublessor on a monthly basis as additional Rent, on the date Base
Rent is due, an amount equal to fifty percent (50%) of the amount by which the
rent payable to Sublessee ("Subrent") under the sublease exceeds the rent due
for the applicable portion of the Sublease Premises after deducting from the
Subrent (A) the actual out-of pocket costs incurred by Sublessee for brokerage
commissions and tenant concessions (which concessions are not reflected in the
reduced Subrent) and (B) the costs of any additional improvements constructed by
Sublessee in connection with the sublease (amortized on a straight line basis
over the term of the sublease). Notwithstanding the foregoing, Sublessee may
assign this Sublease or sublet any portion of the Sublease Premises without
Sublessor's or Master Lessor's consent to any of the following (i) any
corporation which controls, is controlled by or under common control with
Sublessee; (ii) any corporation resulting from the merger or consolidation of
Sublessee; and (iii) any person or entity which acquires all of the assets of
Sublessee as a going concern of the business that is being conducted on the
Sublease Premises (collectively, "Sublessee Affiliate"), provided that such
assignee assumes in full the obligations of Sublessee under the Sublease. Any
right of Sublessor or Master Lessor to terminate the Sublease or the Master
Lease in response to a requested assignment or subletting shall not apply to an
assignment of the Sublease or a subletting of the Sublease Premises to a
Sublessee Affiliate. Sublessee shall have the same assignment and sublease
rights and limitations as provided in section 13.1 of the Master Lease.

         14.      Access to Premises. Master Lessor shall have the same right of
access to the Sublease Premises as Sublessor which right of access is described
in Section 14 of the Master Lease.

         15.      Surrender at End of Term. Upon expiration or termination of
this Sublease, Sublessee shall surrender the Sublease Premises to Sublessor in
good and sanitary order, except for any alterations Sublessee is not required to
remove, normal wear and tear, acts of God, damage, destruction (except to the
extent Sublessee is obligated to restore the same under this Sublease) and
eminent domain covered by the provisions of this Sublease. Sublessee shall
remove from the Sublease Premises all of Sublessee's personal property and trade
fixtures, Sublessee's Equipment and Alterations, and any alterations and
improvements Sublessee is required to remove pursuant to Sublessor's or Master
Lessor's written consent to such alterations and improvements, and shall repair
all damage caused by the removal. Except to the extent caused by Sublessor's or
Master Lessor's or their agents', employees' or invitees', negligence or willful
misconduct, Sublessee shall indemnify Sublessor against all loss or liability
resulting from delay by Sublessee in so surrendering the Sublease Premises,
including without limitation, any claims made by any succeeding tenant, losses
to Sublessor due to lost opportunities to lease to a succeeding tenant, and
reasonable attorneys' fees and costs. Sublessee shall have no

                                       10

<PAGE>

obligation to remove any fixtures, alterations, or personal property placed or
installed in the Sublease Premises prior to the Commencement Date hereof.

         16.      Sublessor Indemnity re: Hazardous Materials.

                  a.       Sublessor will provide to Sublessee copies of the
documents referred to in section 17.4 of the Master Lease.

                  b.       Sublessee shall indemnify, defend and hold Sublessor
harmless from and against any claim, damage, loss, liability, cost or expense
(including reasonable attorneys' fees) arising out of any spill or release of
any Hazardous Substance (as defined in Section 11.6 of the Master Lease which
has been incorporated by reference into this Sublease) on or about the Sublease
Premises by Sublessee, its employees, agents or contractors during the period of
time Sublessee has occupied the Sublease Premises. Sublessor shall indemnify,
defend and hold Sublessee harmless from and against any claim, damage, loss,
liability, cost or expense (including reasonable attorneys' fees) arising out of
any spill or release of any Hazardous Substance (as defined in Section 11.6 of
the Master Lease which has been incorporated by reference into this Sublease) on
or about the Sublease Premises by Sublessor, its employees, agents or
contractors during the period of time Sublessee occupies the Sublease Premises.

                  c.       Sublessor is entitled to indemnification from the
Master Lessor under certain circumstances as provided in Section 11.6 of the
Master Lease. To the extent such indemnification may apply to the benefit of
Sublessee, Sublessor agrees to cooperate with Sublessee to enforce such
indemnity obligation against Master Lessor; provided, however, Sublessee shall
pay any and all costs incurred by Sublessor or Sublessee in connection with the
enforcement thereof for the benefit of Sublessee.

         17.      Signs. Master Lessor shall have the same approval rights with
respect to signs as Sublessor; Sublessor shall use its best efforts to obtain
Master Lessor's approval of signage rights reasonably satisfactory to Sublessee,
so long as such rights do not unreasonably interfere with the rights of
Sublessor under the Master Lease.

         18.      Holding Over. This Sublease shall terminate without further
notice at the expiration of the Sublease term. Any holding over by Sublessee
after expiration or sooner termination of this Sublease without the consent of
Sublessor shall be construed to be a tenancy at sufferance. Base Rent for the
Sublease Premises during any tenancy at sufferance, or if Sublessor shall have
consented to Sublessee's holding over, shall be at a rate equal to 150% of the
Base Rent for the last month of the term, and shall otherwise be on the terms
and conditions herein specified insofar as applicable.

         19.      Brokers. Sublessor and Sublessee each warrants and represents
for the benefit of the other that it has had no dealings with any real estate
broker or agent in connection with the negotiation of this Sublease, and that it
knows of no real estate broker or agent who is or might be entitled to a real
estate brokerage commission or finder's fee in connection with this Sublease.

                                       11

<PAGE>

Sublessor and Sublessee warrant and represent that they have dealt with no real
estate broker in connection with this Sublease.

                  a.       Broker Disclaimer. Sublessor and Sublessee agree and
accept that, except as otherwise expressly stated herein, no broker or agent has
made or conducted any investigation, determination, warranty or representation
with respect to any of the following: (a) the legality of the present or any
possible future use of the Sublease Premises under any federal, state or local
law; (b) the physical condition or square footage of the Sublease Premises; (c)
the terms of the Master Lease or any other relevant legal document or agreement;
or (d) the presence or location of any hazardous materials on or about the
property in which the Sublease Premises are located (including, but not limited
to, asbestos, PCB's, other toxic, hazardous or contaminated substances, and
underground storage tanks).

                  b.       Acknowledgement: The parties acknowledge that they
are not relying on information from any real estate licensee relating to the
field of toxic materials, hazardous waste, underground tanks, and asbestos
contamination, location of the property within or outside a specific flood zone
or special studies seismic area, nor the property's compliance with the
guidelines as set forth in the Americans with Disabilities Act (ADA) regarding
the determination of the condition of the subject Premises, but rather from
their own independently initiated investigations.

         20.      Notices. All notices or demands of any kind required to be
given by Sublessor or Sublessee hereunder shall be in writing and shall be
deemed delivered forty-eight (48) hours after depositing the notice or demand in
the United States Mail, certified or registered, postage prepaid, addressed to
the Sublessor or Sublessee respectively at the addresses set forth after their
signatures at the end of this Sublease. Either party may change its address by
written notice to the other party in accordance with this Section 20. All Base
Rent shall be paid by Sublessee to Sublessor at the same address.

         21.      Condition To Effectiveness of This Sublease. This sublease is
contingent upon Sublessor obtaining the written consent of the Master Lessor to
this Sublease within 15 days of the date hereof. Sublessor and Sublessee
acknowledge and agree that in granting such consent, notwithstanding any other
provisions contained in or implied in this Sublease, Master Lessor shall not be
deemed or construed (a) to have released Sublessor from any responsibility for
the full and timely performance of all obligations of Sublessor as Tenant under
the Master Lease as it pertains to the Sublease Premises, nor (b) to have
authorized Sublessor to act on Master Lessor's behalf in exercising or waiving
any rights, remedies or privileges of Master Lessor as Landlord under the Master
Lease as it pertains to the Sublease Premises, nor (c) to have assumed; incurred
or undertaken any obligations or liabilities running directly to Sublessee with
respect to the Sublease Premises, it being the explicit intention and
understanding of the parties that notwithstanding the incorporation by reference
of the Master Lease into this Sublease (except as specifically excluded by
section 2 above, and as otherwise specifically excluded in this Sublease),
Master Lessor and Sublessor shall look solely to one another for the performance
of their respective obligations with respect to the Sublease Premises as
Landlord and Tenant under the Master Lease, and that Sublessor and Sublessee
shall look solely to one another for the

                                       12

<PAGE>

performance of their respective obligations with respect to the Sublease
Premises under this Sublease. Nothing in this Section 21 is intended, however,
to preclude Sublessee from enforcing, by direct action against Master Lessor,
any rights of Sublessor under the Master Lease to the extent such rights are
expressly assigned by Sublessor to Sublessee pursuant to this Sublease.

         22.      Authority. Each person executing this Sublease on behalf of a
party hereto represents and warrants that he or she is authorized and empowered
to do so and to thereby bind the party on whose behalf he or she is signing.

         23.      Attorneys' Fees. In the event either party shall bring any
action or proceeding for damages or for an alleged breach of any provision of
this Sublease to recover rents, or to enforce, protect or establish any right or
remedy hereunder, the prevailing party shall be entitled to recover reasonable
attorneys' fees and court costs as part of such action or proceeding.

         IN WITNESS WHEREOF, the undersigned have executed this Sublease as of
the dates set forth below.

Sublessor:

METAXEN LLC,
a Delaware limited liability company

By:   /s/ Michael J. Ross
      -----------------------------
      Michael J. Ross, Ph.D.
Its:  President and CEO                      Date 3/25/99

280 East Grand Avenue
South San Francisco, CA 94080

Sublessee:

EXELIXIS PHARMACEUTICALS, INC.,
a Delaware corporation

By:    /s/ George Scangos                           Date____________
       -----------------------
       George Scangos, Ph.D
       President and CEO
       260 Littlefield Avenue
       South San Francisco, CA 94080

                                       13

<PAGE>

                                      EXHIBIT "B-2"

Subject to the provisions of Article 9 of the Master Lease, the following
fixtures and equipment shall remain with_the Sublease Premises and shall be
surrendered by Sublessee at the expiration or earlier termination of the
Sublease:

         ALL FIXED PARTITIONS
         ALL CASE WORK AND BENCHES, SCREWED DOWN OR HARD WIRED TO THE
         BUILDING

Subject to the provisions of Article 9 of the Master Lease, the following
fixtures and equipment shall be removed from the Ground Floor Leased Area and
the Second Floor Leased Area at the expiration or earlier termination of the
Sublease (the "Sublessee Equipment and Alterations"):

                  Centrifuges
                  Tissue Culture Incubators
                  Tissue Culture Hoods
                  All robotic and automated devices purchased by the Sublessee
                  including Robotic Plate, Liquid Handling and Imaging Devices
                  Vibration Isolation Tables
                  Freezers
                  Refrigerator/Freezers
                  Microscopes
                  Free Standing shelving
                  Water treatment systems which are not part of the "house"
                  system

                                       14

<PAGE>

<TABLE>
<S>                       <C>
Subleases

Cytokinetics              8/1/98 - 8/31/00 ($52,250/mo first year, $53,625/mo second year)
                          first year: $3.80/sq ft; second year: $3.80/sq ft
                          13 750 square feet

Exelixis                  3/1/99-5/31/00 (9/30/00) ($25,477/mo)
                          ground floor: $1.80/sq ft                 3,040 Exe only, 4,986 (50%) shared
                          second floor: $3.50/sq ft                 3,019 Exe only, 5,677 (25%) shared
</TABLE>

<TABLE>
<CAPTION>
                                                                                      MetaXen
Who occupies how much space          MelaXen  Cytokinetics   Exelixis    M/E shared     %age
                                     ---------------------------------------------------------
<S>                          <C>     <C>      <C>            <C>         <C>          <C>
                             Ground     4,757     13,750        3040          4968         50%
                             Second    14,984          -        3019          5677         75%

                                       19,741     13,750       6,059        10,645     50,195
</TABLE>