OPKO HEALTH, INC. - and - OTI HOLDINGS LIMITED - and - EACH HOLDER OF EXCHANGEABLE SHARES in the capital of OTI Holdings Limited EXCHANGE AND SUPPORT AGREEMENT DATED: November 28, 2007

EXCHANGE AND SUPPORT AGREEMENT

ARTICLE 1 DEFINITIONS AND INTERPRETATION

1.1

DEFINITIONS

4

1.2

RULES OF INTERPRETATION

7

1.3

ENTIRE AGREEMENT

8

ARTICLE 2 REPRESENTATIONS AND WARRANTIES OF OPKO

2.1

REPRESENTATIONS AND WARRANTIES OF OPKO

8

ARTICLE 3 EXCHANGE RIGHT

3.1

GRANT OF EXCHANGE RIGHT

10

3.2

EXERCISE OF EXCHANGE RIGHT

10

3.3

DELIVERY OF EXCHANGE RIGHT CONSIDERATION

11

3.4

EFFECT OF EXERCISE

3.5

DEEMED EXERCISE OF EXCHANGE RIGHT SUBSEQUENT TO RETRACTION

3.6

NOTICE OF INSOLVENCY EVENT

12

ARTICLE 4 AUTOMATIC EXCHANGE RIGHT

4.1

NOTICE OF OPKO LIQUIDATION EVENT

12

4.2

AUTOMATIC EXCHANGE

13

4.3

CERTIFICATES

13

ARTICLE 5 ECONOMIC EQUIVALENCE

13

5.1

ECONOMIC EQUIVALENCE - OPKO OBLIGATIONS

5.2

ECONOMIC EQUIVALENCE - THE CORPORATION OBLIGATIONS

5.3

COVENANTS REGARDING EXCHANGEABLE SHARES

5.4

ADDITIONAL OPKO COVENANTS

16

5.5

DELIVERY OF OPKO COMMON SHARES

16

5.6

PROVISION OF FUNDS

17

5.7

OWNERSHIP OF COMMON SHARES

17

5.8

OPKO AND AFFILIATES NOT TO VOTE EXCHANGEABLE SHARES

17

5.9

GRANT OF CALL RIGHTS

18

5.10

NOTIFICATION OF CERTAIN EVENTS

18

5.11

QUALIFICATION OF OPKO COMMON SHARES

18

5.12

TENDER OFFERS

19

ARTICLE 6 TAX MATTERS

6.1

RIGHT TO WITHHOLD

19

6.2

SECTION 116 CLEARANCE CERTIFICATE FOR NON-RESIDENT HOLDERS

19

6.3

TRANSFER TAXES

21

ARTICLE 7 REGISTRATION

21

7.1

PIGGYBACK REGISTRATION.

7.2

REGISTRATION EXPENSES.

7.3

OBLIGATIONS OF OPKO.

22

7.4

OBLIGATIONS OF THE HOLDERS.

25

7.5

TERMINATION OF REGISTRATION RIGHTS.

25

7.6

DISPOSITIONS.

25

7.7

SEC RULE144 REPORTING.

25

7.8

INDEMNIFICATION AND CONTRIBUTION.

26

ARTICLE 8 GENERAL

8.1

TRANSFER AND ISSUANCE RESTRICTIONS

29

8.2

LEGENDS

29

8.3

SELLER ACKNOWLEDGEMENTS AND AGREEMENTS

30

8.4

COMPLIANCE WITH OTHER INSTRUMENTS

30

8.5

CHANGES IN CAPITAL OF OPKO AND THE CORPORATION

31

8.6

TERM

31

8.7

ENUREMENT

31

8.8

NOTICES TO PARTIES

31

8.9

NOTICE TO HOLDERS

32

8.10

AMENDMENT

32

8.11

ASSIGNMENT

32

8.12

FURTHER ASSURANCES

32

8.13

EXECUTION AND DELIVERY

33

A.

The parties wish to set out their understanding with respect to certain rights and obligations in connection with the exchange of shares of the Corporation for shares of Opko.

B.

Schedule A shall be automatically amended by the Corporation to include each additional investor that executes a counterpart instrument of accession to this Agreement in the form attached as Schedule B.

(b)

an amount equal to the Outstanding Dividend Amount on such Exchangeable Share on the date of exchange. 

(a)

Consent - Whenever a provision of this Agreement requires an approval or consent and such approval or consent is not delivered within the applicable time limit, then, unless otherwise specified, the Party whose consent or approval is required will be conclusively deemed to have withheld its approval or consent.

(b)

Currency - Unless otherwise specified, all references to money amounts are to the lawful currency of the United States of America.

(c)

Governing Law - This Agreement is a contract made under and is governed by and construed in accordance with the law of the Province of Ontario and the federal laws of Canada applicable in the Province of Ontario.

(d)

Headings - Headings of Articles and Sections are inserted for convenience of reference only and do not affect the construction or interpretation of this Agreement.

(e)

Including - Where the word “including” or “includes” is used in this Agreement, it means “including (or includes) without limitation”.

(f)

Number and Gender - Unless the context otherwise requires, words importing the singular include the plural and vice versa and words importing gender include all genders.

(g)

Severability - If, in any jurisdiction, any provision of this Agreement or its application to any party or circumstance is restricted, prohibited or unenforceable, such provision will, as to such jurisdiction, be ineffective only to the extent of such restriction, prohibition or unenforceability without invalidating the remaining provisions of this Agreement and without affecting the validity or enforceability of such provision in any other jurisdiction or without affecting its application to other Parties or circumstances.

(h)

Statutory references - A reference to a statute includes all regulations made pursuant to such statute and, unless otherwise specified, the provisions of any statute or regulation that amends, supplements or supersedes any such statute or any such regulation.

(i)

Time - Time is of the essence in the performance of the Parties’ respective obligations.

(j)

Time Periods - Unless otherwise specified, time periods within or following which any payment is to be made or act is to be done are calculated by excluding the day on which the period commences and including the day on which the period ends and by extending the period to the next Business Day if the last day of the period is not a Business Day.

(a)

Authorized and Outstanding Capital - At October 25, 2007, the authorized capital stock of OPKO consisted of 500,000,000 shares of common stock, $.01 par value per share, of which as of November 9, 2007 163,214,203 shares were issued or outstanding, fully paid and non-assessable, and 10,000,000 shares of preferred stock, $.01 par value per share, of which 869,366 shares were issued or outstanding, fully paid and non-assessable. OPKO’s common stock has been duly and validly registered pursuant to Section 12(b) of the Exchange Act which registration is in full force and effect.

(b)

Incorporation and Organization - OPKO is a corporation duly organized, validly existing and in good standing under the laws of the State of Delaware and has all necessary corporate power to own all of its property and assets, to incur all of its liabilities and to carry on its business as presently conducted.

(c)

Interest in each Subsidiary - All shares of, or interests in, each of OPKO’s wholly-owned subsidiaries, held directly or indirectly by Opko are owned free and clear of all mortgages, liens, charges, pledges, security interests, encumbrances, claims and demands whatsoever and no person has any right, agreement or option, present or future, contingent or absolute, or any right capable of becoming a right, agreement or option, for the issue or allotment of any unissued shares of each of OPKO’s wholly-owned subsidiaries or any other security convertible into or exchangeable for any shares of each of OPKO’s wholly-owned subsidiaries or to require each of OPKO’s wholly-owned subsidiaries to purchase, redeem or otherwise acquire any of its issued and outstanding shares.

(d)

SEC Filings - Except for the Current Report on form 8-K and certain financial statements of Ophthalmic Technologies Inc. in connection with the initial investment in Ophthalmic Technologies Inc., since March 27, 2007, OPKO has filed all reports, documents and other information required of it to be filed with the SEC (the “OPKO SEC Reports”). The OPKO SEC Reports were prepared in accordance with the requirements of the Securities Act or the Exchange Act, as the case may be, and the rules and regulations of the SEC thereunder applicable to such OPKO SEC Reports. No disclosure included in any of the Parent SEC Reports included any statement that, when made or, if such Parent SEC Reports were subsequently amended, when amended, contained an untrue statement of a material fact or omitted to state a material fact necessary in order to make the statements therein, in light of the circumstances in which such statements were made, not materially misleading.

(e)

Stock Exchange Listing - The outstanding Common Shares of OPKO are listed for trading on the American Stock Exchange, and Opko is, and at all times, has been in material compliance with the by-laws, rules and regulations of the American Stock Exchange.

(f)

No Material Changes - Since the date of the latest financial statements included within a report filed by OPKO with the Securities and Exchange Commission, and except as disclosed in OPKO’s reports filed with the SEC and other than this transaction, there has not been any material change in the assets, liabilities or obligations of Opko or any of OPKO’s wholly-owned subsidiaries, and to OPKO’s knowledge, there has not been any material adverse change in the business, operations or condition (financial or otherwise) or results of the operations of Opko or any of OPKO’s wholly-owned subsidiaries.

(a)

an Insolvency Event;

(b)

the failure of Opko or any Permitted Subsidiary to purchase all or any part of the Exchangeable Shares held by such Holder following exercise of the Liquidation Call Right as provided in the Exchangeable Share Provisions;

(c)

subject to Section 3.1(b), the failure of the Corporation to redeem all the outstanding Exchangeable Shares following a Liquidation Event as provided in the Exchangeable Share Provisions;

(d)

the failure of Opko or any Permitted Subsidiary to purchase all or any part of the Exchangeable Shares held by such Holder following exercise of the Redemption Call Right as provided in the Exchangeable Share Provisions;

(e)

subject to Section 3.2(d), the failure of the Corporation to redeem all the outstanding Exchangeable Shares held by such Holder on the Redemption Date as provided in the Exchangeable Share Provisions;

(f)

the failure of Opko or any Permitted Subsidiary to purchase all or any part of the Exchangeable Shares held by such Holder following exercise of the Retraction Call Right as provided in the Exchangeable Share Provisions; or

(g)

subject to Section 3.1(f), the failure of the Corporation to redeem the Retracted Shares under a Retraction Request as provided in the Exchangeable Share Provisions.

(a)

that the Holder is exercising the Exchange Right;

(b)

the number of Exchangeable Shares in respect of which the Exchange Right is being exercised;

(c)

that the Holder has good title to and owns all the Exchangeable Shares free and clear of all encumbrances, other than those stipulated under the Share Purchase Agreement or the Articles;

(d)

whether the Holder is a non-resident of Canada for the purposes of the Income Tax Act (Canada) (the “Tax Act”);

(e)

the names in which the new certificates representing the Opko Common Shares are to be issued; and

(f)

the name and address of the Person to whom such new certificates are to be delivered.

(a)

Opko will give the Holders notice of each of the following events at the time set forth below:

(i)

in the event of any determination by Opko to institute voluntary liquidation, dissolution or winding-up proceedings with respect to Opko or to effect any other distribution of assets of Opko among its shareholders for the purpose of winding up its affairs, at least 60 days prior to the proposed effective date of such liquidation, dissolution, winding-up or other distribution; and

(ii)

immediately, upon the earlier of (A) receipt by Opko of notice of and (B) Opko otherwise becoming aware of any threatened or instituted claim, suit, petition or other proceedings with respect to the involuntary liquidation, dissolution or winding up of Opko or to effect any other distribution of assets of Opko among its shareholders for the purpose of winding up its affairs.

(b)

Notice of any event (an "Opko Liquidation Event") contemplated by Section 4.1(a)(i) or 4.1(a)(ii) above shall include a brief description of the automatic exchange of Exchangeable Shares for Opko Common Shares provided for in Section 4.2 below.

(a)

Opko or such Permitted Subsidiary, as applicable, will deliver or cause to be delivered to each Holder the Exchange Right Consideration for each Exchangeable Share held by the Holder;

(b)

each Holder will be deemed to have transferred to Opko or such Permitted Subsidiary, as applicable, all of the Holder’s interest in the Exchangeable Shares (which shall be free and clear of all liens and encumbrances, other than those stipulated under the Share Purchase Agreement, or the Articles) and will cease to be a Holder of those Exchangeable Shares;

(c)

the Holder will be deemed to be the holder of the Opko Common Shares delivered to it; and

(d)

the certificates held by the Holder previously representing the Exchangeable Shares will be deemed to represent the Opko Common Shares and other Exchange Right Consideration delivered to the Holder.

(a)

declare or pay or make any distribution (other than a distribution consisting of an issuance referred to in Section 5.1(b)) on the Opko Common Shares unless the Corporation forthwith declares, pays or makes, as the case may be, the same per share dividend or distribution on the Exchangeable Shares as provided in Section 4.1 of the Exchangeable Share Provisions;

(b)

issue or distribute to all of the Holders of the then outstanding Opko Common Shares in respect of the Opko Common Shares held by such holders:

(i)

Opko Common Shares (or securities exchangeable for or convertible into or carrying rights to acquire Opko Common Shares) by way of a share distribution or other distribution; or

(ii)

rights, options or warrants entitling them to subscribe for or to purchase Opko Common Shares (or securities exchangeable for or convertible into or carrying rights to acquire Opko Common Shares),

(c)

effect:

(i)

a subdivision or change of the then outstanding Opko into a greater number of Opko Common Shares;

(ii)

a reduction, combination, consolidation or change of the then outstanding Opko Common Shares into a lesser number of Opko Common Shares;

(iii)

a reclassification or other change of the Opko Common Shares; or

(iv)

an amalgamation, merger, reorganization or other transaction affecting the Opko Common Shares, other than in the event of an Opko Sale pursuant to which a Redemption right is exercised,

(a)

declare or pay any dividend or make any other distribution (other than a dividend or distribution consisting of an issuance referred to in Section 5.2(b)) on the Exchangeable Shares unless Opko forthwith declares, pays or makes, as the case may be, the same per unit distribution on the Opko Common Shares;

(b)

issue to all of the Holders in respect of the Exchangeable Shares held by such Holders:

(i)

Exchangeable Shares (or securities exchangeable for or convertible into or carrying rights to acquire Exchangeable Shares) by way of stock dividend or other distribution; or

(ii)

rights, options or warrants entitling them to subscribe for or to purchase Exchangeable Shares (or securities exchangeable for or convertible into or carrying rights to acquire Exchangeable Shares),

(c)

effect:

(iii)

a subdivision or change of the then outstanding Exchangeable Shares into a greater number of Exchangeable Shares;

(iv)

a reduction, combination, consolidation or change of the then outstanding Exchangeable Shares into a lesser number of Exchangeable Shares;

(v)

a reclassification or other change of the Exchangeable Shares; or

(vi)

an amalgamation, merger, reorganization or other transaction affecting the Exchangeable Shares, other than in the event of an Opko Sale pursuant to which a Redemption right is exercised,

(a)

ensure that the declaration date, record date and payment date for a dividend on the Exchangeable Shares will be the same as the declaration date, record date and payment date for the corresponding dividend on Opko Common Shares;

(b)

advise each Holder sufficiently in advance of any Company Sale or Liquidation Event to allow each Holder to exercise its rights of retraction pursuant to the Exchangeable Share Provisions to receive Opko Common Shares immediately prior to any such event or date;

(c)

duly and timely perform all of their respective obligations, and take all actions and do all things as are necessary or desirable to enable and permit each other to perform their respective obligations, under the Exchangeable Share Provisions; and

(d)

ensure that any redemption of Exchangeable Shares of a Holder in connection with a Company Sale, if requested by such Holder, shall be effective only upon, and will be conditional upon, the closing of the Company Sale.

(a)

not exercise its vote as a shareholder of the Corporation, nor allow any direct or indirect Subsidiary to exercise its own vote as a shareholder of the Corporation, to initiate the voluntary liquidation, dissolution or winding-up of the Corporation nor take any action or omit to take any action that is designed to result in the liquidation, dissolution or winding-up of the Corporation, other than in circumstances where such vote is necessary in order to enable the Corporation to fulfill its obligations under this Agreement or pursuant to the Exchangeable Share Provisions; and

(b)

take all such commercially reasonable actions and do all such commercially reasonable things as are necessary or desirable to enable and permit Opko, the Corporation, or a Permitted Subsidiary, as applicable, in accordance with applicable law, to perform its obligations arising upon the exercise by it of the Liquidation Call Right, the Retraction Call Right or the Redemption Call Right, including without limitation all such actions and all such things as are necessary or desirable to enable and permit Opko, the Corporation, or a Permitted Subsidiary, as applicable, to cause to be delivered Opko Common Shares to the holders of Exchangeable Shares in accordance with the provisions of the Liquidation Call Right, the Retraction Call Right or the Redemption Call Right, as the case may be.

(a)

Subject to Section 5.4, Section 5.8(b) and Section 5.8(c), Opko will appoint and cause to be appointed proxyholders with respect to all Exchangeable Shares from time to time held by it and its Affiliates for the sole purpose of attending each meeting of Holders in order to be counted as part of the quorum for each meeting.

(b)

Opko will not, and will cause its Affiliates not to, exercise any voting rights that may be exercisable by holders of the Exchangeable Shares from time to time in respect of any matter considered at any meeting of Holders of Exchangeable Shares.

(c)

Where Holders (excluding Opko and its Affiliates) of more than two-thirds of the Exchangeable Shares approve the adding to or changing of restrictions or conditions, or the removing or changing of rights or privileges, attaching to the Exchangeable Shares, and such Holders of the Exchangeable Shares do not hold a sufficient number of Exchangeable Shares to cause such action to be approved by written consent of such Holders (as prescribed by applicable Law), Opko will, if it is a holder of Exchangeable Shares, and will cause its Affiliates who are holders of Exchangeable Shares, to execute any resolutions in writing which are executed by such other Holders or to exercise its votes in the same manner as exercised by the Holders of more than two-thirds of the Exchangeable Shares (excluding Opko and its affiliates).

(a)

in the event of any determination by the board of directors of the Corporation to institute voluntary liquidation, dissolution or winding up proceedings with respect to the Corporation or to effect any other distribution of the assets of the Corporation among its shareholders for the purpose of winding up its affairs, at least 60 days prior to the proposed effective date of such liquidation, dissolution, winding up or other distribution;

(b)

immediately, upon the earlier of (i) receipt by the Corporation of notice of, and (ii) the Corporation otherwise becoming aware of, any threatened or instituted claim, suit, petition or other proceedings with respect to the involuntary liquidation, dissolution or winding up of the Corporation or to effect any other distribution of the assets of the Corporation among its shareholders for the purpose of winding up its affairs;

(c)

immediately, upon receipt by the Corporation of a Retraction Request; and

(d)

as soon as practicable upon the issuance by the Corporation of any Exchangeable Shares or rights to acquire Exchangeable Shares.

(a)

Each Holder that is a non-resident of Canada for purposes of the Tax Act (a “Non-resident Holder”) and to whom the Exchangeable Shares are “taxable Canadian property” and not “excluded property” for purposes of the Tax Act must, prior to a disposition of such shares to the Corporation, Opko or any Permitted Subsidiary as may be designated by Opko, deliver to the Payer an amount in Canadian dollars equal to 25% of the fair market value of the Exchangeable Shares to be disposed of, as determined on the date of disposition (the “Up-front Amount”). The Up-front Amount shall be released by the Payer or remitted to the Canada Revenue Agency (the “CRA”) as set forth below.

(b)

If the Up-front Amount has not been delivered to the Payer on, or prior to, the date of disposition of the Exchangeable Shares (the “Effective Date”), the Non-resident Holder must, prior to a disposition of such shares to the Corporation, Opko or any Permitted Subsidiary as may be designated by Opko, deliver a section 116 clearance certificate (a “Clearance Certificate”) to the Payer.

(c)

If a Clearance Certificate having a certificate limit as defined in subsection 2 of Section 116 of the Tax Act (the “Certificate Limit”) at least equal to the fair market value for the Exchangeable Shares being disposed of has not been delivered to the Payer on or prior to the Effective Date, the Payer shall withhold 50% of the proceeds of disposition otherwise deliverable to the Non-resident Holder. If a Clearance Certificate has been delivered to the Payer on or before the Effective Date and the Certificate Limit is less than the 50% of the fair market value of the Exchangeable Shares being disposed of, the Payer shall withhold 50% of the amount by which the proceeds of disposition otherwise payable to the Non-resident Holder exceeds the Certificate Limit. Any amount so withheld (the “Withheld Amount”) shall be released by the Payer or remitted to the Canada Revenue Agency (the “CRA”) as set forth below.

(d)

If on or before the 27th day of the month following the calendar month which includes the Effective Date (the “Remittance Date”), the Payer receives from the Non-resident Holder a Clearance Certificate with a Certificate Limit at least equal to the fair market value of the Exchangeable Shares disposed of, the Payer shall, promptly after receipt of such Clearance Certificate, deliver to the Non-resident Holder the Withheld Amount or the Up-front Amount, as may be applicable, plus any interest earned thereon (less any applicable withholding taxes).

(e)

If on or before the Remittance Date, the Payer does not receive from the Non-resident Holder a Clearance Certificate, or receives a Clearance Certificate with a Certificate Limit that is less than the fair market value of the Exchangeable Shares being disposed of, then, unless the CRA has issued a letter confirming that the CRA will not enforce the remittance of funds as is normally required under subsection 116(5) of the Tax Act and that the Payer will not be charged interest or penalties if it delays the remittance of amounts in respect of the disposition of the Exchangeable Shares until further instructed by the CRA (a “Comfort Letter”), the Payer shall remit to the Receiver General for Canada (the “Receiver General”) from the Withheld Amount or the Up-front Amount, as may be applicable, an amount equal to 25% of the fair market value of the Exchangeable Shares disposed of (or, if a Clearance Certificate is received but with a Certificate Limit less than the fair market value of the Exchangeable Shares disposed of, an amount equal to 25% of the difference between the fair market value of the Exchangeable Shares disposed of and the Certificate Limit) and shall remit to the Non-resident Holder such portion of the Withheld Amount or the Up-front Amount, as may be applicable, not required to be remitted to CRA (if any), together with any interest earned thereon (less applicable withholding taxes).

(f)

If the CRA has issued a Comfort Letter, the Payer shall not make any remittance to the Receiver General on the date that would otherwise be the Remittance Date and if a Clearance Certificate is subsequently received while the Comfort Letter remains in effect, with a Certificate Limit at least equal to the fair market value of the Exchangeable Shares being disposed of, the Payer shall, promptly after receipt of such certificate, remit to the Non-resident Holder the Withheld Amount or the Up-front Amount, as may be applicable, together with any interest earned thereon, less any applicable withholding taxes. If notification from the CRA is received that the Comfort Letter is no longer in effect, the date of receipt of such notification shall be deemed to be the Remittance Date for the purposes of this section.

(g)

Any amount that the Payer withholds from the proceeds of disposition otherwise payable to the Non-resident Holder pursuant to the provisions hereof shall be treated as having been paid to the Non-resident Holder on account of the proceeds of disposition on the date of disposition.

(a)

Beginning on the date of this Agreement, OPKO will notify all Holders of Registrable Securities in writing at least 10 days prior to the filing of any registration statement under the Securities Act for purposes of a public offering of OPKO Common Shares by OPKO (including, but not limited to, registration statements relating to secondary offerings of OPKO Common Shares, but excluding registration statements relating to employee benefit plans or with respect to corporate reorganizations or other transactions under SEC Rule 145) and will afford each such Holder an opportunity to include in such registration statement up to 100% of such Registrable Securities held by such Holder, subject to Section 7.1(b). Each Holder desiring to include in any such registration statement part of the Registrable Securities held by it will, within 5 days after the above-described notice from OPKO (the “Holder Notice Period”), so notify OPKO in writing. Such notice will state the intended method of disposition of the Registrable Securities by such Holder as well as the number of Registrable Securities proposed by such Holder to be included in such registration statement.

(b)

If the registration statement under which OPKO gives notice under this Section 7.1(b) is for an underwritten offering, OPKO will so advise the Holders of Registrable Securities as a part of such notice. In such event, the right of any Holder to be included in a registration pursuant to this Section  7.1(b) will be conditioned upon such Holder’s participation in such underwriting and the inclusion of such Holder’s Registrable Securities in the underwriting to the extent provided herein. All Holders proposing to distribute their Registrable Securities through such underwriting will enter into an underwriting agreement in customary form with the underwriter or underwriters selected for such underwriting by OPKO. Notwithstanding any other provision of this Section  7.1(b), if the underwriter determines that marketing factors require a limitation of the number of shares to be underwritten, the number of shares that may be included in the underwriting will be allocated first to OPKO.

(c)

OPKO will have the right to terminate or withdraw any registration initiated by it under this Section 7.1 prior to the effectiveness of such registration whether or not any Holder has elected to include securities in such registration.

(a)

prepare and file with the SEC a registration statement with respect to such Registrable Securities and use its reasonable efforts to cause such registration statement to become effective and keep such registration statement effective for at least 180 days or, if earlier, until (i) the participating Holder or Holders have completed the distribution related thereto or (ii) the Registrable Securities are no longer required to be registered;

(b)

prepare and file with the SEC such amendments and supplements to such registration statement and the prospectus used in connection with such registration statement as may be necessary to comply with the provisions of the Securities Act with respect to the disposition of all securities covered by such registration statement;

(c)

in the event of any underwritten public offering, enter into and perform its obligations under an underwriting agreement, in usual and customary form, with the managing underwriter or underwriters of such offering. Each Holder participating in such underwriting will also enter into and perform its obligations under such an agreement;

(d)

promptly notify each Holder of Registrable Securities covered by such registration statement at any time when a prospectus relating thereto is required to be delivered under the Securities Act upon learning of the happening of any event as a result of which the prospectus included in such registration statement, as then in effect, includes an untrue statement of a material fact or omits to state a material fact required to be stated therein or necessary to make the statements therein not misleading and, at the request of the Holders, OPKO shall prepare a supplement or amendment to such prospectus so that, as thereafter delivered to the purchasers of such Registrable Securities, such prospectus shall not contain an untrue statement of a material fact or omit to state any fact necessary to make the statements therein not misleading in the light of the circumstances then existing;

(e)

furnish to each Holder and to each underwriter such number of copies of the registration statement and the prospectus included therein (including each preliminary prospectus) as such Persons reasonably may request in order to facilitate the intended disposition of the Registrable Securities covered by such registration statement;

(f)

use its best efforts (i) to register or qualify the Registrable Securities covered by such registration statement under the securities or “blue sky” laws of such jurisdictions as the sellers of Registrable Securities or, in the case of an underwritten public offering, the managing underwriter reasonably shall request, (ii) to prepare and file in those jurisdictions such amendments (including post effective amendments) and supplements, and take such other actions, as may be necessary to maintain such registration and qualification in effect at all times for the period of distribution contemplated thereby and (iii) to take such further action as may be necessary or advisable to enable the disposition of the Registrable Securities in such jurisdictions, provided, that OPKO shall not for any such purpose be required to qualify generally to transact business as a foreign corporation in any jurisdiction where it is not so qualified or to consent to general service of process in any such jurisdiction;

(g)

permit a single firm of counsel designated as selling stockholders' counsel by the Holders to review the registration statement and all amendments and supplements thereto for a reasonable period of time prior to their filing.

(h)

if such registration involves an underwritten offering, furnish a legal opinion of the Corporation’s counsel, dated the date of the closing under the underwriting agreement, with respect to the registration statement, each amendment and supplement thereto, the prospectus included therein (including the preliminary prospectus) and other documents relating thereto, in customary form and covering such matters as are customarily covered by legal opinions of issuers’ counsel in such public offerings. 

(i)

if such registration involves an underwritten offering, furnish a legal opinion of the Corporation’s counsel, dated the date of the closing under the underwriting agreement, with respect to the registration statement, each amendment and supplement thereto, the prospectus included therein (including the preliminary prospectus) and other documents relating thereto, in customary form and covering such matters as are customarily covered by legal opinions of issuers’ counsel in such public offerings

(j)

make available for inspection by each seller of Registrable Securities, any underwriter participating in any distribution pursuant to such registration statement, and any attorney, accountant or other agent retained by such seller or underwriter, all relevant financial and other records, pertinent corporate documents and properties of OPKO, and cause OPKO's officers, directors and employees to supply all information reasonably requested by any such seller, underwriter, attorney, accountant or agent in connection with such registration statement;

(k)

provide a transfer agent and registrar, which may be a single entity for the Registrable Securities not later than the effective date of the Registration Statement;

(l)

take all actions reasonably necessary to facilitate the timely preparation and delivery of certificates (not bearing any legend restricting the sale or transfer of such securities) representing the Registrable Securities to be sold pursuant to the Registration Statement and to enable such certificates to be in such denominations and registered in such names as the Sellers or any underwriters may reasonably request;

(m)

take all other reasonable actions necessary to expedite and facilitate the registration of the Registrable Securities pursuant to the Registration Statement; and

(n)

advise each Holder of Registrable Securities covered by such registration statement and, if requested by any such Holder, confirm such advice in writing:

(i)

when such registration statement, and any amendment thereto, has been filed with the SEC and when the registration statement or any post-effective amendment thereto has become effective;

(ii)

of any request by the SEC for amendments or supplements to such registration statement or the prospectus included therein or for additional information;

(iii)

of the issuance by the SEC of any stop order suspending effectiveness of the registration statement or the initiation of any proceedings for that purpose; and

(iv)

of the receipt by OPKO of any notification with respect to the suspension of the qualification of the securities included in the registration statement for sale in any jurisdiction or the initiation of any proceeding for such purpose.

(a)

Make and keep public information available, as those terms are understood and defined in SEC Rule 144 or any similar or analogous rule promulgated under the Securities Act.

(b)

File with the SEC, in a timely manner, all reports and other documents required of OPKO under the Exchange Act;

(c)

As long as a Holder owns any Registrable Securities, furnish to such Holder promptly upon request: a written statement by OPKO as to its compliance with the reporting requirements of SEC Rule 144, the Securities Act, and the Exchange Act, a copy of the most recent annual or quarterly report of OPKO and such other reports and documents so filed by OPKO; and such other reports and documents as a Holder may reasonably request in availing itself of any rule or regulation of the SEC allowing it to sell any such securities without registration.

(a)

In the event of a registration of any of the Registrable Securities under the Securities Act pursuant to Section 7.1, OPKO will indemnify and hold harmless each seller of such Registrable Securities thereunder, any underwriter (as defined in the Securities Act) for such seller, and each other Person, if any, who controls such seller or underwriter within the meaning of the Securities Act or the Exchange Act, from and against, and pay or reimburse them for, any losses, claims, reasonable expenses, damages or liabilities to which such seller, underwriter or controlling Person may become subject under the Securities Act, the Exchange Act or otherwise, insofar as such losses, claims, expenses, damages or liabilities (or actions in respect thereof) arise out of or are based upon any untrue statement or alleged untrue statement of any material fact contained in any registration statement under which such Registrable Securities were registered under the Securities Act pursuant to Section 7.1, any preliminary prospectus or final prospectus contained therein, or any amendment or supplement thereof, or arise out of or are based upon the omission or alleged omission to state therein a material fact required to be stated therein or necessary to make the statements therein not misleading, or any violation or alleged violation of the Securities Act, the Exchange Act, any state securities or blue sky laws and specifically will reimburse each such seller, underwriter and controlling Person for any legal or other expenses reasonably incurred by it in connection with investigating or defending any such loss, claim, damage, liability or action; provided, that OPKO will not be liable in any such case if and to the extent that any such loss, claim, expense, damage or liability arises out of or is based upon OPKO's reliance on an untrue statement or alleged untrue statement or omission or alleged omission so made in conformity with information furnished by any such seller, underwriter or controlling Person in writing specifically for use in such registration statement or prospectus; and provided further, that OPKO shall not be liable to the extent that any such loss, claim, expense, damage or liability (or action in respect thereof) arises out of or is based upon an untrue statement or alleged untrue statement or omission in such registration statement corrected in an amendment or supplement to the registration statement, such amendment or supplement was delivered to the indemnified party in sufficient quantities and a reasonable period of time prior to the closing of any offering and the indemnified party failed to deliver or failed to cause to be delivered such registration statement as so amended or supplemented to the Person asserting such loss, claim, expense, damage or liability.

(b)

In the event of a registration of any of the Registrable Securities under the Securities Act pursuant to Section 7.1, each seller of such Registrable Securities thereunder, severally and not jointly, will indemnify and hold harmless OPKO, each Person, if any, who controls OPKO within the meaning of the Securities Act, each officer of OPKO who signs the registration statement, each director of OPKO and any underwriter and any controlling Person of such underwriter from and against all losses, claims, reasonable expenses, damages or liabilities, joint or several, to which OPKO or such officer, director, underwriter or controlling Person may become subject under the Securities Act, Exchange Act or otherwise, insofar as such losses, claims, expenses, damages or liabilities (or actions in respect thereof) arise out of or are based upon reliance on any untrue statement or alleged untrue statement of any material fact contained in the registration statement under which such Registrable Securities were registered under the Securities Act, any preliminary prospectus or final prospectus contained therein, or any amendment or supplement thereof, or arise out of or are based upon the omission or alleged omission to state therein a material fact required to be stated therein or necessary to make the statements therein not misleading, and will reimburse OPKO and each such officer, director, underwriter and controlling Person for any legal or other expenses reasonably incurred by them in connection with investigating or defending any such loss, claim, expense, damage, liability or action; provided, that such seller will be liable hereunder in any such case if and only to the extent that any such loss, claim, expense, damage or liability arises out of or is based upon an untrue statement or alleged untrue statement or omission or alleged omission made in reliance upon and in conformity with information pertaining to such seller, as such, furnished in writing to OPKO by such seller specifically for use in such registration statement or prospectus; and provided, further, that the liability of each seller hereunder shall be limited to the proportion of any such loss, claim, expense, damage or liability which is equal to the proportion that the public offering price of the Registrable Securities sold by such seller under such registration statement bears to the total public offering price of all securities sold thereunder

(c)

 Notwithstanding the foregoing, the indemnity provided in this ARTICLE 7 shall not apply to amounts paid in settlement of any such loss, claim, expense, damage or liability if such settlement is effected without the consent of such seller;

(d)

Promptly after receipt by an indemnified party hereunder of notice of the commencement of any action (including any governmental action), such indemnified party shall, if a claim in respect thereof is to be made against the indemnifying party hereunder, notify the indemnifying party in writing thereof, but the delay so to notify the indemnifying party shall not relieve it from any liability which it may have to such indemnified party other than under this Section 7.8 and shall only relieve it from any liability which it may have to such indemnified party under this Section 7.8 if and to the extent the indemnifying party is materially prejudiced by such delay. In case any such action shall be brought against any indemnified party and it shall notify the indemnifying party of the commencement thereof, the indemnifying party shall be entitled to participate in and, to the extent it shall wish, to jointly with any other indemnifying party similarly notified, assume and undertake the defence thereof with counsel satisfactory to such indemnified party, and, after notice from the indemnifying party to such indemnified party of its election so to assume and undertake the defence thereof, the indemnifying party shall not be liable to such indemnified party under this Section 7.8 for any legal expenses subsequently incurred by such indemnified party in connection with the defence thereof provided, that if the defendants in any such action include both the indemnified party and the indemnifying party and the indemnified party shall have reasonable defences available to it which are different from or additional to those available to the indemnifying party or if the interests of the indemnified party reasonably may be deemed to conflict with the interests of the indemnifying party, the indemnified party shall have the right to select a separate counsel and to assume such legal defences and otherwise to participate in the defence of such action, with the reasonable expenses and fees of such separate counsel and other expenses related to such participation to be reimbursed by the indemnifying party as incurred.

(e)

If the indemnification provided for in this Section 7.8 is held by a court of competent jurisdiction to be unavailable to an indemnified party with respect to any loss, claim, expense, damage or liability referred to therein, then the indemnifying party, in lieu of indemnifying such indemnified party hereunder, shall contribute to the amount paid or payable by such indemnified party as a result of such loss, claim, expense, damage or liability in such proportion as is appropriate to reflect the relative fault of the indemnifying party on the one hand and of the indemnified party on the other in connection with the untrue statement or alleged untrue statement or omission or alleged omission or violation or alleged violation that resulted in such loss, claim, expense, damage or liability as well as any other relevant equitable considerations. The relative fault of the indemnifying party and of the indemnified party shall be determined by reference to, among other things, whether the untrue statement or alleged untrue statement or omission or alleged omission or violation or alleged violation relates to information supplied or acts or omissions by the indemnifying party or by the indemnified party and the parties’ relative intent, knowledge, access to information, and opportunity to correct or prevent such statement, omission or violation; provided further, that, in no event shall any contribution of a holder or Registrable Securities under this Section 7.8 exceed the net proceeds from the offering received by such holder.

(f)

(e) The obligations of the Parties under this Section 7.8 shall survive the completion of any offering of Registrable Securities in a registration statement under Section 7.1; provided that any such indemnification obligations shall not extend beyond the period proscribed by the applicable statute of limitations (and all extensions thereof) with respect to such action or claim; and provided further, that if notice is given under this Section 7.8 with respect to any matter entitling a party to indemnification hereunder prior to the applicable expiration date, such indemnification obligation shall continue indefinitely in respect of the applicable claim until it is finally resolved.

(a)

no Exchangeable Shares may be Transferred unless, in addition to such Transfer complying with all provisions related to Transfers set forth in this Agreement and in the constating documents of the Corporation, concurrently with such transfer the transferee enters into this Agreement by executing a counterpart instrument of accession in the form attached as Schedule B; and

(b)

no additional Exchangeable Shares may be issued by the Corporation to any Person who is not a Holder without Joint Approval, and if Joint Approval is obtained unless, concurrently with such issuance, the Person to whom such shares are issued enters into this Agreement by executing a counterpart instrument of accession in the form attached as Schedule B.

(a)

if to the Corporation, to Opko, any Permitted Subsidiary, or their Affiliates, to:

(b)

and if to the Holders in accordance with Section 8.9.

(c)

Any such communication so given or made shall be deemed to have been given or made and to have been received on the day of delivery if delivered, or on the day of faxing or sending by other means of recorded electronic communication, provided that such day in either event is a Business Day and the communication is so delivered, faxed or sent before 4:30 p.m. on such day. Otherwise, such communication shall be deemed to have been given and made and to have been received on the next following Business Day. Any such communication sent by mail shall be deemed to have been given and made and to have been received on the fifth Business Day following the mailing thereof; provided however that no such communication shall be mailed during any actual or apprehended disruption of postal services. Any such communication given or made in any other manner shall be deemed to have been given or made and to have been received only upon actual receipt.

(d)

Any Party may from time to time change its address under this Section by notice to the other Party given in the manner provided by this Section.

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