Exhibit 10.5

 

Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions marked [***].

 

AMENDMENT NO. 4 TO COLLABORATION AND LICENSE AGREEMENT

 

This Amendment No. 4 to the Collaboration and License Agreement (this
"Amendment") is made and entered into as of January 29, 2018 (“Effective Date”),
by and between Kyowa Hakko Kirin Co., Ltd., a company organized and existing
under the laws of Japan, with an address at 1-9-2 Ohtemachi, Chiyoda-ku, Tokyo,
100- 0004, Japan ("KHK") and Ultragenyx Pharmaceutical Inc., a company organized
and existing under the laws of the State of Delaware, with an address at 60
Leveroni, Novato, California 94949, USA ("UGNX'').

 

RECITALS

 

 

A.

KHK and UGNX are parties to a Collaboration and License Agreement dated August
29, 2013, regarding the joint development and commercialization of KRN23 (the
“Licensed Product”), an Amendment No. 1 to Collaboration and License Agreement
effective as of September 24, 2015, an Amendment 2 effective as of November 28,
2016, and an Amendment 3 effective September 29, 2017 (collectively, the
"Collaboration Agreement").

 

B.

Pursuant to Section 13.6 of the Collaboration Agreement, KHK wishes to conduct
the Commercialization of the Licensed Product with UGNX in the Profit Share
Territory through its Affiliate, Kyowa Kirin Inc. (“KKUS”).

 

C.

With the first approval and Commercialization of the Licensed Product in the
United States anticipated in the near future, the Parties desire to further
clarify their relationship related to the Profit Share Territory under the
Collaboration Agreement.

 

D.

Terms defined in the Collaboration Agreement shall have the same meaning in this
Amendment as they have in the Collaboration Agreement.

 

E.

All terms and conditions of the Collaboration Agreement not expressly addressed
in this Amendment shall remain in full force and effect.

 

NOW, THEREFORE, in consideration of the foregoing premises and the mutual
covenants herein contained, the parties hereby agree as follows:

 

1.

The following sentence will be added to the end of Section 5.4.  

“In addition to the above, KKI, on behalf of Kyowa Hakko Kirin, will enter into
a Safety Agreement with UGNX, that will supersede the above Safety Agreement and
describe detailed pharmacovigilance processes and responsibilities of each
Party.”

2.

A new Section 5.9 shall be added that provides as follows:

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Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions marked [***].

“5.9 BLA Transfer. [***] (or a mutually agreed-to period), of approval by FDA of
a Biologics Licensing Application for Licensed Product (“BLA”), UGNX shall
transfer ownership of any BLA to KKUS.

(a)Promptly after transferring the BLA to KKUS, UGNX shall send FDA a letter of
the type described in 21 C.F.R. § 314.72, informing the agency of the transfer
of the BLA to KKUS.  
(b)At the same time, KKUS will send FDA a letter accepting the transfer of
ownership and notifying FDA that KKUS is appointing UGNX as its agent for
regulatory matters associated with each BLA.

(c)UGNX shall be responsible for contact to and from FDA, including emails and
other correspondence, except as otherwise agreed to in writing by the
Parties.  UGNX shall immediately share all FDA contacts with KKUS.  The Parties
will agree on an electronic method to accomplish this sharing.”

 

3.

A new Section 5.10 shall be added that provides as follows:

“5.10 Labeling and Packaging. To the extent of commercialization in the United
States, in accordance with 21 C.F.R. § 201.1(h)(5), the label, packaging and
labeling of the Licensed Product will state as follows:

Manufactured by:

Kyowa Hakko Kirin Co., Ltd

Takasaki Plant

100-1 Hagiwara-machi, Takasaki

Gunma 370-0013, Japan

 

Manufactured for:

Kyowa Kirin Inc.

235 Route 202/206 Suite 6,

Bedminster NJ 07921

Distributed by:

Ultragenyx Pharmaceutical Inc.
Novato, CA 94949 USA”

However, should FDA require a change to the above wording, the Parties agree to
amend it accordingly.”

4.

A new Section 5.11 shall be added that provides as follows:

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Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions marked [***].

“5.11 Other Reports to FDA and other Regulatory Authorities with respect to the
Commercialization of the Licensed Product in the United States.

 

(a)

Each party shall be responsible for reporting payments or other transfers of
value (“POTV”) made by that Party or any of its Affiliates or any of their
respective Third Party contractors related to the conduct of the
Commercialization of the Licensed Products or otherwise in connection with this
Agreement to Recipients (as defined below), as required under the Sunshine Laws.
“Sunshine Laws” means Applicable Laws requiring collection, reporting and
disclosure of POTVs to certain healthcare providers, entities and individuals,
including, without limitation, relevant provisions of the Patient Protection and
Affordable Health Care Act of 2010 and implementing regulations
thereunder.  “Recipients” means healthcare providers, teaching hospitals and/or
other persons for whom ownership interest, transfers of value or payments must
be reported under the Sunshine Laws.

 

(b)

KKUS shall be responsible for drafting all BLA supplements dealing with
manufacturing changes or issues.  KKUS will submit these supplements to UGNX for
its review and approval [***] prior to submission to FDA.

 

(c)

UGNX shall be responsible for drafting all other BLA supplements and FDA
submissions.  UGNX shall submit all routine or planned BLA supplements and other
submissions to KKUS for its review and approval [***] prior to submission to
FDA.  For non-routine submissions to FDA that require expedited processing, UGNX
will discuss and agree with KKUS on timing for the KKUS review.”

 

5.

A new Section 5.12 shall be added that provides as follows:

“5.12 National Drug Code Numbers. To the extent of the Commercialization of the
Licensed Product in the United States, UGNX will obtain National Drug Code
numbers (NDCs) for the various presentations of the Licensed Product.  KKUS will
obtain its own NDCs for Licensed Product prior to the Profit Share Territory
Transition Date.   After the Profit Share Territory Transition Date, UGNX grants
KKUS the right to use its NDCs to the extent necessary to sell, manage, transfer
and dispose of Licensed Product inventory bearing UGNX’s NDCs. The Parties agree
to cooperate with each other to ensure a seamless transition of inventory and
associated tasks.”

 

6.

A new Section 6.5 shall be added that provides as follows:

 

“6.5 Marketing Materials Review Process with Respect to the Commercialization of
the Licensed Product in the United States.

6.5.1 Brand Book. KKUS and UGNX will jointly create a brand book and message
platform for the Licensed Product, which will contain key claims and imagery.

6.5.2 KKUS Core Material Review.  KKUS [***] will have access to review core
Marketing Materials before they are approved for distribution by UGNX or sent to
the FDA on form 2253. [***]  At the request of either Party, a meeting will be
held by telephone or in person to resolve any matters related to regulatory or
legal.  Subject to Section 6.4 of this

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Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions marked [***].

Agreement, UGNX shall have the final authority to determine the content of
Marketing Materials through the day immediately preceding the Profit Share
Territory Transition Date.  [***]

 

7.

A new Section 6.6 shall be added that provides as follows:

“6.6 Third Party Logistics. To the extent of the Commercialization of the
Licensed Product in the United States, KKUS will select and contract with a
Third Party logistics provider (“Third Party Logistics Provider”) to manage and
control inventory of the Licensed Product, including picking, packing and
shipping of Licensed Product and invoicing UGNX’s customers of the Licensed
Product (“Customer”). Legal title to Licensed Product shall remain with KKUS
until transfer to Customer or other Third Party destination specified by
UGNX.  UGNX will have direct access to the inventory and sales information
generated by the Third Party Logistics Provider.  [***]  Risk to inventory until
the point of transfer to the Customer or other Third Party destination shall
remain with KKUS.”

 

8.

A new Section 6.7 shall be added that provides as follows:

“6.7.  Transition of Commercial and Regulatory Activities in the United States.

6.7.1. Quarterly Commercial Meeting.  To the extent of the Commercialization of
the Licensed Product in the United States, during the entire five-year
collaboration period, UGNX and KKUS shall meet each quarter under the guidance
of the JCT to review significant commercial developments related to the Licensed
Product.

6.7.2 Year Preceding Transition. To the extent of the Commercialization of the
Licensed Product in the United States, UGNX and KKUS agree to cooperate with
each other and use best efforts to ensure a seamless transition of the Licensed
Product from UGNX to KKUS upon the Profit Share Territory Transition Date.  The
following activities shall occur during the year preceding the Profit Share
Territory Transition Date:

(a)KKUS and UGNX shall form a Transition Committee that will hold a transition
planning meeting to map and outline steps and key activities and timing.

(b)The Transition Committee shall draft plans for transition of supply,
packaging, and labeling responsibilities, regulatory responsibilities and
reporting (including Sunshine Laws, government pricing and adverse experience
reporting), clinical trials, advisory boards, grants and sponsorships,
continuing medical education programs, and communications with Customers and
other third parties.  These plans will include transfer to KKUS of all documents
and data that will assist in such transitions.

(c)Any required contract amendments with third parties will be initiated.  UGNX
will cooperate as requested by KKUS to complete the assignment process.

(d) KKUS and UGNX will create a schedule that will allow KKUS personnel to
observe in real time existing patient support service programs and other
interactions with service providers and Customers, and to accompany UGNX
personnel to these observations.  The schedule will be reasonable and not
significantly disrupt the work of UGNX personnel.

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Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions marked [***].

6.7.3 Training. UGNX and KKUS will train KKUS personnel on the programs,
procedures and tasks that will be transitioned from UGNX to KKUS.”

9.

Section 7.5 shall be deleted and replaced as follows:

“7.5 Foreign Currency Exchange. For any currency conversion from the currency of
one country in which the Licensed Products are sold into U.S. Dollars (or
another currency if applicable) required in determining the Net Sales or any
royalties or revenue share, such conversion shall be equal to the average
exchange rate, over the applicable quarter, calculated at the conversion rate as
reported by OANDA (www.oanda.com), or an equivalent resource as agreed by the
parties, on the last Business Day of the quarter in which the applicable Net
Sales were made.”

 

10.

A new Section 7.8 shall be added that provides as follows:

“7.8 Sale of Priority Review Voucher.  UGNX and KHK agree that they will share
equally in the pre-tax net proceeds of the sale of the priority review voucher,
defined as the sales price minus the costs associated with the sale.”

 

11.

A new Section 7.9 shall be added that provides as follows:

“7.9. Pricing and Cash Management with Respect to the Commercialization of the
Licensed Product in the United States.

7.9.1KKUS will establish and maintain ownership of a Lockbox Account (as defined
below) for all payments from Customers.  KKUS will provide UGNX with the ability
to view the Lockbox Account.  For purposes of this agreement, “Lockbox Account”
shall mean a remittance service whereby KKUS establishes an electronic lockbox
account that is accessible by KKUS’s bank in order to receive Customers’
payments for Licensed Products invoiced by Third Party Logistics Provider under
UGNX’s name.

7.9.2UGNX and KKUS agree to form a treasury committee that will oversee cash
management issues with respect to the Licensed Product distributed by UGNX and
invoiced by Third Party Logistics Provider under UGNX’s name, the composition of
the treasury committee will be approved by the JSC.  KKUS, however, [***]

7.9.3    UGNX and KKUS agree to form a pricing committee for the purpose of
establishing predefined pricing parameters to be jointly agreed upon, as well as
for reviewing and approving on-going contractually offered discounts, rebates
and other proposed price concessions.  This pricing committee will operate
within the guidelines established by the JSC.  UGNX [***]

7.9.4    UGNX shall have the right to review gross to Net Sales of the Licensed
Product which will be calculated by KKUS, on a quarterly basis.

7.9.5    If KKUS cannot book revenues of the Licensed Product invoiced by Third
Party Logistics Provider under UGNX’s name due to changes in accounting
guidance, the

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Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions marked [***].

“Sales Order To Cash Process” (as defined below) will be amended as agreed by
both Parties to achieve KKUS revenue recognition. “Sales Order To Cash Process”
shall mean: A business process for receiving and processing Customer orders and
payments.  This includes order creation, order fulfillment, distribution,
invoicing, Customer payment collection and cash allocation.”

 

12.

A new Section 9.3 shall be added that provides as follows:

“9.3 Licensed Product-Related Contracts with Respect to Commercialization of the
Licensed Product in the United States.

9.3.1 UGNX will upon request of KKUS send or otherwise make a copy of all
supply, pricing, rebate, discount and other commercial contracts related to
Licensed Product within [***]  Other commercial contracts set forth above shall
include sponsorships, grants and charitable contributions but not such things as
minor consulting agreements.  

9.3.2 UGNX shall ensure that all Customer contracts provide UGNX and KKUS with
access to and the right to audit the data supporting Net Sales calculations, as
described in Section 9.1 of this Agreement.  All commercial contracts related to
the Commercialization of the Licensed Product in the United States entered into
by UGNX and the Customer shall permit assignment to KKUS upon UGNX’s written
notice to the corresponding Customer and without any consent of such
Customer.  Notwithstanding the foregoing, UGNX shall not assign any commercial
contracts to KKUS without KKUS’s prior written consent for such assignment.”

13.

A new section 14.6 and 14.7 shall be added that provides as follows:

 “Additional Indemnity.

14.6  UGNX agrees to defend, hold harmless and indemnify the KHK lndemnitees
from and against any and all Losses incurred by a KHK Indemnitee in connection
with any and all Third Party claims arising or resulting from any document,
other communication or activity used or made by UGNX in connection with Licensed
Product in the Profit Share Territory that has not been provided to KHK based on
the process described in Section 6.5 of the Agreement.  Nothing contained in
this Section 14.6 is intended to limit the existing indemnity obligations of
UGNX set forth in Section 14.1.  Any claim for indemnity under this Section 14.6
shall follow the procedure set forth in Section 14.3.

14.7  KHK agrees to defend, hold harmless and indemnify the UGNX lndemnitees
from and against any and all Losses incurred by a UGNX Indemnitee in connection
with any and all Third Party claims arising or resulting from any document,
other communication or activity used or made by KKUS in connection with Licensed
Product in the Profit Share Territory that has not been reviewed and approved by
UGNX in accordance with the terms of the Agreement. Nothing contained in this
Section 14.7 is intended to limit the existing indemnity obligations of KHK set
forth in Section 14.1.  Any claim for indemnity under this Section 14.7 shall
follow the procedure set forth in Section 14.3.

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Certain information in this document has been omitted and filed separately with
the Securities and Exchange Commission. Confidential treatment has been
requested with respect to the omitted portions marked [***].

 

 

 

IN WITNESS WHEREOF, the Parties have executed this Amendment, by their
representatives duly thereunto authorized as of the Effective Date.

 

KYOWA HAKKO KIRIN CO., LTD

By:/s/ Masahi Miyamoto

Name:Masahi Miyamoto

Title:Director of the Board, Managing

Executive Officer; Director, Corporate
Strategy & Planning Department

 

Date:January 29, 2018

ULTRAGENYX PHARMACEUTICAL INC.

By: /s/ Emil D. Kakkis

Name: Emil D. Kakkis

Title: President and Chief Executive Officer

 

Date:January 29, 2018

 

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