Opthea Ltd — Major Shareholding Notification 2008

May 11, 2008

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12 May 2008

The Companies Section The Australian Stock Exchange Limited South Tower, Rialto Level 45 525 Collins Street MELBOURNE VIC 3000

Dear Sir/Madam

Cease to be a Substantial holder of Metabolic Pharmaceuticals Limited

We enclose Form 605 “Notice of Ceasing to be a Substantial Holder” with respect to a holding in Metabolic Pharmaceuticals Limited by Polychip Pharmaceuticals Pty Ltd (“Polychip”), a wholly owned subsidiary of Circadian Technologies Limited.

The notice is in reference to the sale by Polychip of the balance of its holding of 36,012,701 Metabolic ordinary shares as recently announced by Circadian.

Yours faithfully

Natalie Korchev Company Secretary

Level 1, 10 Wallace Avenue, Toorak, Victoria 3142, Australia P: +61 (3) 9826 0399 Circadian Technologies Limited F: +61 (3) 9824 0083 ABN 32 006 340 567 www.circadian.com.au

FORM 605

Corporations Act 2001 Section 671B

NOTICE OF CEASING TO BE A SUBSTANTIAL HOLDER

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To: METABOLIC PHARMACEUTICALS LIMITED

ACN: 083 866 862

1. Details of substantial holder (1)

Name: POLYCHIP PHARMACEUTICALS PTY LTD (a wholly owned subsidiary of Circadian Technologies Limited)

ACN: 006 455 456

The holder ceased to be a substantial holder on 12/5/2008 The previous notice was given to the company on 12/1/2007 The previous notice was dated 12/1/2007

2. Changes in relevant interests

Particulars of each change in, or change in the nature of, a relevant interest (2) of the substantial holder or an associate (3) in voting securities of the company or scheme, since the substantial holder was last required to give a substantial holding notice to the company or scheme are as follows:

Date ofchange	Person whoserelevant interestchanged	Nature of change (4)	Considerationgiven inrelation tochange (5)	Class (6) andnumber ofsecuritiesaffected	Person’svotesaffected(no. ofshares)
12/5/2008	PolychipPharmaceuticalsPty Ltd	Sale of shares – off-market transaction	$0.048 per share	Ordinary shares36,012,701	36,012,701

3. Changes in association

The persons who have become associates (3) of, ceased to be associates of, or have changed the nature of their association (7) with, the substantial holder in relation to voting interests in the company or scheme are as follows:

as follows:
Name and ACN (ifapplicable)	**Nature of association **
Not applicable

6. Addresses

The addresses of persons named in this form are as follows:

Name	Address (Registered Office)
PolychipPharmaceuticalsPtyLtd	Level 1,10 WallaceAvenue,Toorak, Victoria
Circadian Technologies Limited	Level 1, 10 Wallace Avenue, Toorak, Victoria

Signed by: Natalie Korchev Company Secretary

Dated: 12 May 2008