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AMENDMENT TO DEVELOPMENT AND LICENSE AGREEMENT

AMENDMENT AGREEMENT to Development and License Agreement effective as of 8 May
2016 (“the Agreement”) between EirGen Pharma Limited, West Side Business, Old
Kilmeaden, Waterford, Ireland (“OPKO”) on the one part and Vifor Fresenius
Medical Care Renal Pharma Ltd, Rechenstrasse 37, 9014 St. Gallen, Switzerland
(“VF”) on the other part.

Background
The Parties have now agreed to amend the Agreement with effect as of 5 May 2020
as set out in this Amendment Agreement.

1.The Parties have agreed to insert a new Section 1.48: “Middle East” shall mean
Algeria, Bahrain, Egypt, Golan Heights, Iran, Iraq, Iraqi Kurdistan, Israel,
Jordan, Kuwait, Lebanon, Libya, Mauritania, Morocco, Oman, Palestinian
territories, Qatar, Saudi Arabia, Sudan, Syria, Tunisia, United Arab Emirates,
and Yemen.

2.The Parties have agreed to amend Section 1.43 as follows.

Section 1.43 is hereby amended to exclude the following jurisdictions from the
Territory: Mexico, South Korea, the Middle East and all countries of Africa
(“Excluded Countries”).

3.The Parties have agreed to insert a new Section 2.4:

2.4 Territory

VF agrees, ***, to promptly transfer to OPKO, if any, all results, analyses,
reports, Product data, technology, know-how, regulatory applications or filings,
and other information in whatever form developed or generated regarding past and
ongoing clinical, development or regulatory activity concerning the Product in
the Excluded Countries.

4.The Parties have agreed to delete and replace the existing Section 5.2 with
the following new Section 5.2:

5.2 Milestone Payments.

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As additional consideration for the rights under the Patents, OPKO Trademarks,
and OPKO Technology granted to VF in this Agreement, VF shall pay non-refundable
and non-creditable milestone payments to OPKO in the amounts and upon the
occurrence of the events set forth below. Each such payment shall be made within
*** Business Days of the achievement or occurrence of the milestone event. Each
milestone payment will be payable only one time. For purposes of clarity, more
than one of the Net Sales and regulatory approval milestones may be met during
the same Agreement Year and, in that case, each such milestone would be payable.
For example, if during one Agreement Year there were Net Sales of the Product in
the Territory of ***, and it was the first Agreement Year in which Net Sales of
the Product in the Territory exceeded ***, *** and ***, then VF would owe all of
the ***, the *** and the *** milestone payments and no similar milestone
payments would be due in any following Agreement Year if the Net Sales in the
Territory exceeded ***.
Milestone Milestone Payment
First New Drug Approval in *** for the
treatment of secondary hyperparathyroidism in
*** patients with vitamin D insufficiency ***

First New Drug Approval in *** for the
treatment of secondary hyperparathyroidism in
*** patients with vitamin D insufficiency ***

First New Drug Approval in *** for the
treatment of secondary hyperparathyroidism in
*** patients with vitamin D insufficiency ***

First New Drug Approval in *** for the
treatment of secondary hyperparathyroidism in
*** patients with vitamin D insufficiency ***

First Commercial Sale in ***. ***
 *** ***;

and ***, then the milestone owed and payable to OPKO
will be equal to that corresponding pro rata percentage *** between *** and ***
that is obtained. For example, *** obtained is ***, OPKO shall be entitled to a
*** milestone payment of ***. *** per day. For the avoidance of doubt, OPKO
shall be entitled to receive the milestone payments described herein based on
*** irrespective of any additional dosage provided in a ***.

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***:
if *** / Daily Dose ***;

and ***, then the milestone owed and payable to OPKO
will be equal to that corresponding pro rata percentage of the *** that is
obtained. For example, if the *** obtained is ***, OPKO shall be entitled to a
*** milestone payment of ***.

***:
if *** / Daily Dose ***;
and if the ***, then the milestone owed and payable to OPKO
will be equal to that corresponding pro rata percentage *** between *** that is
obtained. For example, if the *** obtained is ***, OPKO shall be entitled to a
*** milestone payment of ***.

First time aggregate Net Sales of the Product
in the Territory exceed ***
in an Agreement Year ***

First time aggregate Net Sales of the Product
in the Territory exceed ***
in an Agreement Year ***

First time aggregate Net Sales of the Product
in the Territory exceed ***
in an Agreement Year ***

First time aggregate Net Sales of the Product
in the Territory exceed *** in an
Agreement Year ***

5.The Parties have agreed to delete and replace the existing Section 5.4 with
the following new Section 5.4:

5.4 Minimum Royalty.
Beginning on the first day of the first Calendar Quarter after the Product First
Commercial Sale, for the periods set forth in the table below, VF shall be
obligated to pay OPKO a minimum royalty (the “Minimum Royalty”) to the

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extent the aggregate Royalty Payments due for the applicable period are below
the following amounts, ***
Period Minimum Royalty
The first *** consecutive Calendar Quarters
beginning on the first day of the first Calendar Quarter after the Product First
Commercial Sale, and each *** consecutive Calendar Quarter
thereafter ***

For purposes of clarity, if the total Royalty Payments due under Section 5.3
with respect to each Minimum Royalty period are greater than the applicable
Minimum Royalty for the same period, no Minimum Royalty amount shall be payable
by VF with respect to such period. To the extent that the total Royalty Payments
due under Section 5.3 with respect to a period are less than the Minimum Royalty
for the same period, VF shall pay OPKO the difference between the total Royalty
Payments and the Minimum Royalty. The calculation for the first period to
determine if anything is due under this Section 5.4 is made after *** Calendar
Quarters based on the total Royalty Payments due under Section 5.3 with respect
to such *** Calendar Quarters when compared to the Minimum Royalty of ***.
Thereafter, the calculation for subsequent periods is made for periods of ***
Calendar Quarters each, comparing Royalty Payments due under Section 5.3 with
respect to the period to the Minimum Royalty of ***. The Minimum Royalty
obligation under this Section 5.4 shall terminate as of the end of the
applicable *** Calendar Quarter period ending immediately prior to the Calendar
Quarter in which: (a) a Competitive Product comes on the market in at least ***
Major Countries and there is a Royalty Payment Reduction in *** country or (b)
the Royalty Term expires for a Product in at least *** Major Countries.

6.The Parties have agreed to delete and replace the existing Section 8.1 with
the following new Section 8.1:

8.1  VF Efforts.
Subject to the terms and conditions of this Agreement, VF agrees to use
Commercially Reasonable Efforts to (a) commence the regular commercial
distribution, use, and sale of the Product in the Field in each Major Country as
soon as commercially practicable, and (b) continue diligently thereafter to
commercialize, market, promote and sell the Product in the Field in the
Territory

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for each indication for which the Product has received Regulatory Approval in
the Territory.
*** if it is determined, by mutual agreement of VF and OPKO through the JSC,
that *** in such country or another country.

Except as expressly amended herein, the Agreement shall remain in full force and
effect.

In Witness Whereof, the Parties have caused this Amendment Agreement to be
executed by their duly authorised representatives as of the dates listed below.

EirGen Pharma, Ltd.
Vifor Fresenius Medical Care Renal Pharma Ltd

/s/ Steven D. Rubin
Print name: Steven D. Rubin
Title: Director
Date: May 4, 2020
/s/ Christoph Springer
Print name: Christoph Springer
Title: Chief Strategy Officer
Date: 05-May-20

/s/ Adam Logal
Print name: Adam Logal
Title: Director
Date: May 4, 2020
/s/ Oliver P. Kronenberg
Print name: Oliver P. Kronenberg
Title: Group General Counsel
Date: 05-May-20