Document:

Exhibit
10.16

 

***Certain
identified information has been omitted from this exhibit because it is both (i) not material and (ii) would likely cause competitive
harm to the Registrant if publicly disclosed. Such omitted information is indicated by brackets (“[...***...]”) in this exhibit.
***

 

AMENDMENT
#1 TO THE

 

INVESTIGATOR
SPONSORED RESEARCH AGREEMENT

AMGEN PROTOCOL NO. 20119244

 

BY
AND BETWEEN

 

THE
BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY FOR STANFORD UNIVERSITY, ON BEHALF OF [...***...],

 

AND

 

AMGEN
INC.

 

This
Amendment #1 (this “Amendment”) to the Agreement (as defined below) is entered into as of February 27, 2017 (the “Amendment
Effective Date”) by and between Amgen Inc., a Delaware corporation having its principal place of business at One Amgen Center Drive,
Thousand Oaks, CA 91320-1799 (“Amgen”) and The Board of Trustees of the Leland Stanford Junior University for Stanford
University, having a location at 3000 El Camino Real, Bldg 5, Suite 300, Palo Alto, CA 94306 (“Institution”),
on behalf of [...***...] (“Principal Investigator”). Capitalized terms used but not otherwise defined in this Amendment
shall have the meanings assigned to such terms in the Agreement.

 

RECITALS

 

WHEREAS,
Amgen, Institution and Principal Investigator have entered into an Investigator Sponsored Research Agreement, Amgen Protocol No.
20119244, dated June 18, 2013 (the “Agreement”); and

 

WHEREAS,
the parties to the Agreement desire to amend the Agreement, pursuant to Section 15.1 of the Agreement, in order to expand the
scope of the proposed investigations to be conducted under the Agreement and to make certain other changes as described herein;

 

NOW
THEREFORE, in consideration of the foregoing and for other good and valuable consideration, the receipt and sufficiency of which
is hereby acknowledged, the parties hereto hereby agree as follows:

 

1.
Scope of Work.

 

		A.	Section 1.1
                                            of the Agreement is hereby deleted in its entirety and replaced with the following:

 

“1.1
The initial study (the “Initial Study”) and any subsequent study under this Agreement (a “Subsequent
Study” and all Subsequent Studies, together with the Initial Study, collectively, the “Study”) will be
conducted under an Investigational New Drug Application (“IND”) filed with the United States Food and Drug
Administration (“FDA”) by the Principal Investigator. It will be the responsibility of the Principal
Investigator to maintain each IND and comply with all reporting and other obligations associated with each IND.”

 

     

     

    

 

Execution Copy

 

		B.	Section 1.2
                                            of the Agreement is hereby deleted in its entirety and replaced with the following:

 

“1.2 Protocol.
The protocol for the Initial Study is identified as protocol number 20119244, and entitled “A Monoclonal antibody that
depletes endogenous blood stem cells and enables chemotherapy-free transplants in SCID patients,” as amended (the
“Initial Protocol”). The protocol for any Subsequent Study (a “Subsequent Protocol”) shall be
approved in writing by Amgen prior to the initiation of any Subsequent Study (such approval not to be unreasonably withheld,
conditioned or delayed). For purposes of this Agreement, “Protocol” shall mean, as context reasonably requires,
either (a) the Initial Protocol or a Subsequent Protocol, as applicable to the Initial Study or a Subsequent Study, or
(b) collectively, the Initial Protocol and every Subsequent Protocol. The Initial Protocol will guide the performance of the
Initial Study, and the applicable Subsequent Protocol will guide the performance of any Subsequent Study.”

 

2.
Performance Period. In the first sentence of Section 2, (a) each instance of the word “Study” is hereby
deleted and replaced with the words “Initial Study” and (b) each instance of the word “Protocol” is hereby
deleted and replaced with the words “Initial Protocol”.

 

3.
Final Report. The second sentence of Section 3.2 is hereby deleted in its entirety and replaced with the following: “A
final draft of the manuscript resulting from the Initial Study or any Subsequent Study, as applicable, will serve as a final report to
be provided to Amgen for such study; however, in the event a manuscript is not forthcoming for the Initial Study or any Subsequent Study,
a final report will be submitted to Amgen for such study, including a summary of study accrual, results of all data analysis and final
conclusions.”

 

4.
Option. Section 5.2 of the Agreement is hereby deleted in its entirety and replaced with the following:

 

“5.2
Amgen shall have the unrestricted right to freely utilize all such Data in whatever manner it desires. All Data shall be the
property of Institution. Institution hereby grants Amgen an exclusive option to take an exclusive, worldwide license under the Data
and other intellectual property rights of Institution as set forth in more detail in Schedule C, with the right to sublicense,
to develop, make, have made, use, offer for sale, sell, import and otherwise exploit Study Drug (and derivatives and modifications
thereof) (“Option”).

 

Amgen’s
right to exercise its Option will extend until the date (the “Option Expiration Date”) that is three (3) months
after the date that (a) neither Institution nor Principal Investigator is conducting, or has any plans to conduct, the Initial Study
or any Subsequent Study, (b) the final report for the Initial Study and every Subsequent Study, in each case, as contemplated in
Section 3.2, have been provided to Amgen, and (c) Institution provides written notice to Amgen confirming that the statements
set forth in clauses (a) and (b) above are true. For the avoidance of doubt, if, following the delivery of the notice described
in clause (c) of the preceding sentence (whether or not the Option has already expired), any of the statements in clauses (a)
or (b) of the preceding sentence become untrue, then Institution shall promptly notify Amgen thereof and the Option shall continue
to survive (and, if applicable, shall be reinstated and continue to survive) in accordance with the terms hereof.

 

    	Amgen ref. no. [...***...]	2	 

     

    

 

Execution Copy

 

If
Amgen does not exercise its Option or fails to provide written notice of execution of its Option to Institution prior to the Option Expiration
Date, Amgen will grant Institution a license based on the terms as outlined in Schedule C. In the event Amgen exercises its Option,
Institution will grant Amgen a license based on the terms as outlined in Schedule C.

 

In
the event Amgen exercises its Option at a time when the Initial Study or any Subsequent Study is ongoing, then the parties hereto shall
discuss in good faith and cooperate to develop a plan for the transition of the Program (as defined in Schedule C, Subject Matter)
from Institution to Amgen; provided however that Institution shall be entitled to complete any Initial Study or Subsequent Study ongoing
at the time the Option is executed; provided further, however, that Institution and the Principal Investigator shall consider in good
faith any comments or suggestions relating to such ongoing study from Amgen.”

 

5.
Schedule C.

 

		A.	The
                                            first sentence of the provision in Schedule C of the Agreement next to the title “Subject
                                            Matter” is hereby deleted in its entirety and replaced with the following sentence:
                                            “The parties would enter into a definitive agreement (“the Agreement”)
                                            which would provide for an exclusive option (“the Option”) for Amgen to license
                                            on an exclusive basis Stanford’s program related to the use of AMG 191 for the
                                            purpose of depleting endogenous blood stem cells in patients for whom hematopoietic cell
                                            transplantation is indicated (“the Program”).”
	 	 	 

		B.	The
                                            provision in Schedule C of the Agreement next to the title “Field”
                                            is hereby deleted in its entirety and replaced with the following: “The use of AMG 191
                                            for the purpose of depleting endogenous blood stem cells in patients for whom hematopoietic
                                            cell transplantation is indicated.”
	 	 	 

		C.	The
                                            following row in Schedule C under the title “Milestone Payments”:

 

	“First
    [...***...] in a Phase 3 Clinical Trial	$[...***...]”

 

is
hereby deleted in its entirety and replaced with the following:

 

	“First
    [...***...] in a Phase 3 Clinical Trial for [...***...]	$[...***...]
	First
    [...***...] in a Phase 3 Clinical Trial for [...***...]	$[...***...]
	First
    [...***...] in a Phase 3 Clinical Trial for [...***...]	$[...***...].”

 

The
“$[...***...]” next to the term “TOTAL” under the title “Milestone Payments” in Schedule C
is hereby deleted in its entirety and replaced with “$9M.”

 

6.
Full Force and Effect. Except as expressly set forth in this Amendment, the Agreement remains in full force and effect.

 

7. Miscellaneous.
This Amendment, and the Agreement as modified hereby, contains all of the terms agreed to by the parties hereto regarding the
subject matter hereof and thereof and supersedes any prior oral or written agreements, understandings or arrangements between the
parties hereto as to the subject matter hereof and thereof. This Amendment may not be amended, modified, altered or supplemented
except by means of a written agreement or other instrument executed by the parties hereto. This Amendment may be executed in one or
more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same
instrument. Each Party may execute this Amendment by facsimile transmission or in PDF format sent by electronic mail. Facsimile or
PDF signatures of authorized signatories of the parties hereto will be deemed to be original signatures, will be valid and binding
upon the parties hereto and, upon delivery, will constitute due execution of this Amendment. This Amendment shall be deemed to have
been entered into and shall be construed and enforced in accordance with the laws of the State of California without giving effect
to any choice or conflict of laws provision.

 

[signature
page follows]

 

    	Amgen ref. no. [...***...]	3	 

     

    

 

IN
WITNESS WHEREOF, the parties hereto have executed this Amendment to the Agreement as of the day and year first above written.

 

	 	 	AMGEN INC.
	 	 	 	 
	LEGAL DEPT	 	/s/ Sean Harper
	EMM	 	Name:  	Sean E. Harper
	/s/ EMM	 	Title: 	EVP Research & Development
	 	 	 	 
	 	 	THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
	 	 	 	 
	 	 	/s/ Stefani Shek
	 	 	Name: 	Stefani Shek
	 	 	Title:	Associate Director
	 	 	 	Industrial Contracts Office
	 	 	 	 
	 	 	/s/ Judith Shizuru
	 	 	Judith Shizuru

 

SIGNATURE PAGE TO

AMENDMENT #1 TO THE INVESTIGATOR SPONSORED RESEARCH AGREEMENT

AMGEN PROTOCOL NO. 20119244Exhibit 10.17

 

***Certain identified information has been omitted
from this exhibit because it is both (i) not material and (ii) would likely cause competitive harm to the Registrant if publicly disclosed.
Such omitted information is indicated by brackets (“[...***...]”) in this exhibit. ***

 

AMENDMENT #2 TO THE

 

INVESTIGATOR SPONSORED RESEARCH AGREEMENT

AMGEN PROTOCOL NO. 20119244

 

BY AND BETWEEN

 

THE BOARD OF TRUSTEES OF THE LELAND STANFORD
JUNIOR UNIVERSITY

FOR STANFORD UNIVERSITY, ON BEHALF OF [...***...],

 

AND

 

AMGEN INC.

 

This Amendment #2 (this
“Amendment”) to the Agreement (as defined below) is entered into as of November 15, 2017 (the “Amendment Effective
Date”) by and between Amgen Inc., a Delaware corporation having its principal place of business at One Amgen Center Drive, Thousand
Oaks, CA 91320-1799 (“Amgen”) and The Board of Trustees of the Leland Stanford Junior University for Stanford University,
having a location at 3000 El Camino Real, Bldg 5, Suite 300, Palo Alto, CA 94306 (“Institution”), on behalf
of [...***...] (“Principal Investigator”). Capitalized terms used but not otherwise defined in this Amendment
shall have the meanings assigned to such terms in the Agreement.

 

RECITALS

 

WHEREAS, Amgen, Institution
and Principal Investigator have entered into an Investigator Sponsored Research Agreement, Amgen Protocol No. 20119244, dated June 18,
2013 (the “Agreement”) and amended as of February 27, 2017; and

 

WHEREAS, the parties
to the Agreement desire to further amend the Agreement, pursuant to Section 15.1 of the Agreement, in order to document the parties’
understanding that Stanford has the authority to amend the Study Drug Investigator’s Brochure;

 

NOW THEREFORE, in consideration
of the foregoing and for other good and valuable consideration, the receipt and sufficiency of which is hereby acknowledged, the parties
hereto hereby agree as follows:

 

1. Schedule B.

 

Section 9 (Study Drug Labeling)
of Schedule B of the Agreement is hereby deleted in its entirety and replaced with the following:

 

“Stanford will be responsible
for maintaining and updating the Investigator’s Brochure and DCSI applicable to the Study Drug.”

 

2. Full Force
and Effect. Except as expressly set forth in this Amendment, the Agreement remains in full force and effect.

 

3. Miscellaneous.
This Amendment, and the Agreement as modified hereby, contains all of the terms agreed to by the parties hereto regarding the subject
matter hereof and thereof and supersedes any prior oral or written agreements, understandings or arrangements between the parties hereto
as to the subject matter hereof and thereof. This Amendment may not be amended, modified, altered or supplemented except by means of a
written agreement or other instrument executed by the parties hereto. This Amendment may be executed in one or more counterparts, each
of which shall be deemed an original, but all of which together shall constitute one and the same instrument. Each Party may execute this
Amendment by facsimile transmission or in PDF format sent by electronic mail. Facsimile or PDF signatures of authorized signatories of
the parties hereto will be deemed to be original signatures, will be valid and binding upon the parties hereto and, upon delivery, will
constitute due execution of this Amendment. This Amendment shall be deemed to have been entered into and shall be construed and enforced
in accordance with the laws of the State of California without giving effect to any choice or conflict of laws provision.

 

[signature
page follows]

 

    	 	 	 

     

    

 

IN WITNESS WHEREOF,
the parties hereto have executed this Amendment to the Agreement as of the day and year first above written.

 

	 	Legal Dept
	 	 
	 	EMM
	 	/s/ EMM
	 	 	 
	 	AMGEN INC.
	 	 	 
	 	/s/ Desmond Padhi
	 	Name:	Desmond Padhi
	 	Title:	Vice President, Medical Sciences
	 	 	 
	 	THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY
	 	 
	 	/s/ Stefani Shek
	 	Name:	Stefani Shek
	 	Title:	Associate Director
	 	 	Industrial Contracts Office
	 	 	 
	 	/s/ Judith Shizuru
	 	Judith Shizuru

 

SIGNATURE PAGE TO

AMENDMENT #2 TO THE INVESTIGATOR SPONSORED RESEARCH
AGREEMENT

AMGEN PROTOCOL NO. 20119244

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