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Exhibit 10.2

        CONFIDENTIAL TREATMENT REQUESTED
UNDER 17 C.F.R. §§ 200.80(b)4, AND 240.24

AMENDMENT NUMBER ONE TO
DEVELOPMENT AND LICENSE AGREEMENT
BETWEEN
ELI LILLY AND COMPANY AND
ISIS PHARMACEUTICALS, INC.

        This Amendment Number One (the "Amendment") to the Development and
License Agreement between Eli Lilly and Company ("Lilly") and ISIS
Pharmaceuticals, Inc. ("ISIS"), effective August 14, 2001 (the "Agreement") is
made effective as of June 5, 2003.

1.The parties hereby mutually agree to amend the Agreement as follows:

Exhibit C, Development Plan, to the Agreement is hereby deleted in its entirety
and replaced with the revised Exhibit C attached hereto.

2.In consideration of the activities outlined in the revised Development Plan,
and in satisfaction of all outstanding invoices and currently accrued payment
due from either party to the other related to the Agreement, Lilly agrees to pay
ISIS the sum of [***] to be paid by Lilly to ISIS via wire transfer within ten
(10) days of the effective date of this Amendment. This payment constitutes the
entire compensation for the Development Plan. Upon receipt of such payment, Isis
will have no further claim against Lilly for any payment whatsoever under either
the original Exhibit C to the Agreement or the amended Exhibit C attached
hereto. The parties agree that ISIS will not undertake any additional activity
related to the Agreement without the prior written consent of Lilly. ISIS waives
its right to payment or reimbursement for any such activities undertaken without
Lilly's prior consent.

        IN WITNESS WHEREOF, each of Lilly and ISIS have caused this Amendment to
be signed by its duly authorized representatives.

 
 
 
 
  ELI LILLY AND COMPANY   ISIS PHARMACEUTICALS, INC.
 
 
 
 
  By: /s/  CHARLES E. GOLDEN      

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  By: /s/  B. LYNNE PARSHALL      

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  Name: Charles E. Golden

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  Name: B. Lynne Parshall

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  Date: June 3, 2003

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  Date: June 5, 2003

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Exhibit C
Development Plan
[***]

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AMENDMENT NUMBER ONE TO DEVELOPMENT AND LICENSE AGREEMENT BETWEEN ELI LILLY AND
COMPANY AND ISIS PHARMACEUTICALS, INC.