Document:

EX-4.2

 Exhibit 4.2 

SUPPLEMENTAL INDENTURE 
 DATED
OCTOBER 1, 2020 
 UNION ELECTRIC COMPANY 

TO 
 THE BANK OF NEW YORK MELLON,

 AS TRUSTEE 
  

 
 (SUPPLEMENTAL TO
THE INDENTURE OF MORTGAGE AND DEED OF TRUST DATED JUNE 15, 1937, AS AMENDED, EXECUTED BY UNION ELECTRIC COMPANY TO THE BANK OF NEW YORK MELLON, AS TRUSTEE) 
  

 
 2.625% First
Mortgage Bonds due 2051 
 This instrument was prepared by Chonda J. Nwamu, Esq., Senior Vice President, General Counsel and Secretary
of Union Electric Company, 1901 Chouteau Avenue, St. Louis, Missouri 63103, (314) 621-3222. 
 WHEN
RECORDED MAIL TO: 
 Craig W. Stensland 
 Union Electric
Company 
 1901 Chouteau Avenue 
 St. Louis, MO 63103 

 SUPPLEMENTAL INDENTURE, dated the 1st day of October, Two thousand and twenty
(2020) made by and between UNION ELECTRIC COMPANY, a corporation organized and existing under the laws of the State of Missouri (hereinafter called the “Company”), party of the first part, and THE BANK OF NEW YORK MELLON,
formerly The Bank of New York (successor trustee to Bank of America, National Association, formerly Boatmen’s Trust Company), a bank existing under the laws of the State of New York (hereinafter called the “Trustee”), as Trustee under
the Indenture of Mortgage and Deed of Trust dated June 15, 1937, hereinafter mentioned, party of the second part: 
 WHEREAS,
the Company has heretofore executed and delivered to the Trustee its Indenture of Mortgage and Deed of Trust, dated June 15, 1937, as amended May 1, 1941, April 1, 1971, February 1, 1974, July 7, 1980, February 1, 2000,
August 15, 2002 and May 15, 2012 (said Indenture of Mortgage and Deed of Trust as so amended, being hereinafter referred to as the “Original Indenture”), to secure the payment of the principal of and the interest (and premium, if
any) on all bonds at any time issued and outstanding thereunder, and indentures supplemental thereto dated June 15, 1937, May 1, 1941, March 17, 1942, April 13, 1945, April 27, 1945, October 1, 1945, April 11,
1947, April 13, 1949, September 13, 1950, December 1, 1950, September 20, 1951, May 1, 1952, March 1, 1954, May 1, 1955, August 31, 1955, April 1, 1956, July 1, 1956, August 1, 1957,
February 1, 1958, March 1, 1958, November 5, 1958, March 16, 1959, June 24, 1959, December 11, 1959, August 17, 1960, September 1, 1960, October 24, 1960, June 30, 1961, July 1, 1961,
August 9, 1962, September 30, 1963, November 1, 1963, March 12, 1965, April 1, 1965, April 14, 1966, May 1, 1966, February 17, 1967, March 1, 1967, February 19, 1968, March 15, 1968,
August 21, 1968, April 7, 1969, May 1, 1969, September 12, 1969, October 1, 1969, March 26, 1970, April 1, 1970, June 12, 1970, January 1, 1971, April 1, 1971, September 15, 1971,
December 3, 1973, February 1, 1974, April 25, 1974, February 3, 1975, March 1, 1975, June 11, 1975, May 12, 1976, August 16, 1976, April 26, 1977, October 15, 1977, November 7, 1977,
December 1, 1977, August 1, 1978, October 12, 1979, November 1, 1979, July 7, 1980, August 1, 1980, August 20, 1980, February 1, 1981, October 8, 1981, August 27, 1982, September 1, 1982,
December 15, 1982, March 1, 1983, June 21, 1984, December 12, 1984, June 11, 1985, March 1, 1986, May 1, 1986, May 1, 1990, December 1, 1991, December 4, 1991, January 1, 1992,
September 30, 1992, October 1, 1992, December 1, 1992, February 1, 1993, February 18, 1993, May 1, 1993, August 1, 1993, October 1, 1993, January 1, 1994, February 1, 2000, August 15, 2002,
March 5, 2003, April 1, 2003, July 15, 2003, October 1, 2003, February 1, 2004 (eight separate indentures supplemental thereto), May 1, 2004, September 1, 2004, January 1, 2005, July 1, 2005,
December 1, 2005, June 1, 2007, April 1, 2008, June 1, 2008, March 1, 2009, September 1, 2012, April 1, 2014, March 15, 2015, June 1, 2017, April 1, 2018, March 1, 2019, September 15, 2019,
and March 1, 2020, respectively, have heretofore been entered into between the Company and the Trustee; and 
 WHEREAS, the
following Bonds have heretofore been issued by the Company under the Original Indenture and remain outstanding: 

(1)    $184,000,000 principal amount of First Mortgage Bonds, Senior Notes Series BB, which are
described in the Supplemental Indenture dated March 5, 2003, all of which are outstanding at the date of the execution hereof; 

(2)    $60,000,000 principal amount of First Mortgage Bonds, Environmental Improvement Series 2004A
(1998A Bonds), which are described in the Supplemental Indenture dated February 1, 2004, all of which are outstanding at the date of the execution hereof; 

(3)    $50,000,000 principal amount of First Mortgage Bonds, Environmental Improvement Series 2004B
(1998B Bonds), which are described in the Supplemental Indenture dated February 1, 2004, all of which are outstanding at the date of the execution hereof; 

(4)    $50,000,000 principal amount of First Mortgage Bonds, Environmental Improvement Series 2004C
(1998C Bonds), which are described in the Supplemental Indenture dated February 1, 2004, all of which are outstanding at the date of the execution hereof; 

(5)    $47,500,000 principal amount of First Mortgage Bonds, Environmental Improvement Series 2004H
(1992 Bonds), which are described in the Supplemental Indenture dated February 1, 2004, all of which are outstanding at the date of the execution hereof; 

 (6)    $300,000,000 principal amount of First Mortgage
Bonds, Senior Notes Series II, which are described in the Supplemental Indenture dated July 1, 2005, all of which are outstanding at the date of the execution hereof; 

(7)    $350,000,000 principal amount of First Mortgage Bonds, Senior Notes, Series NN, which are
described in the Supplemental Indenture dated March 1, 2009, all of which are outstanding at the date of the execution hereof; 

(8)    $485,000,000 principal amount of First Mortgage Bonds, Senior Notes, Series OO, which are
described in the Supplemental Indenture dated September 1, 2012, all of which are outstanding at the date of the execution hereof; 

(9)    $350,000,000 principal amount of First Mortgage Bonds, Senior Notes, Series PP, which are
described in the Supplemental Indenture dated April 1, 2014, all of which are outstanding at the date of the execution hereof; 

(10)    $400,000,000 principal amount of First Mortgage Bonds, Senior Notes, Series QQ, which are
described in the Supplemental Indenture dated March 15, 2015, all of which are outstanding at the date of the execution hereof; 

(11)    $400,000,000 principal amount of First Mortgage Bonds, Senior Notes, Series RR, which are
described in the Supplemental Indenture dated June 1, 2017, all of which are outstanding at the date of the execution hereof; 

(12)    $425,000,000 principal amount of 4.000% First Mortgage Bonds, due 2048, which are described in the
Supplemental Indenture dated April 1, 2018, all of which are outstanding at the date of the execution hereof; 

(13)    $450,000,000 principal amount of 3.50% First Mortgage Bonds, due 2029, which are described in the
Supplemental Indenture dated March 1, 2019, all of which are outstanding at the date of the execution hereof; 

(14)    $330,000,000 principal amount of 3.25% First Mortgage Bonds due 2049, which are described in the
Supplemental Indenture dated September 15, 2019, all of which are outstanding at the date of the execution hereof; and 

(15)    $465,000,000 principal amount of 2.95% First Mortgage Bonds due 2030, which are described in the
Supplemental Indenture dated March 1, 2020, all of which are outstanding at the date of the execution hereof; 
 WHEREAS, the
Company on August 31, 1955 acquired all of the properties of Union Electric Power Company, the Subsidiary as defined in Article I of the Original Indenture, upon the dissolution of the Subsidiary; the Company, by Supplemental Indenture
dated August 31, 1955, conveyed all of the properties so acquired (other than property of the character defined as excepted property in the granting clauses of the Original Indenture) to the Trustee upon the terms and trusts in the Original
Indenture and the indentures supplemental thereto set forth for the equal and proportionate benefit and security of all present and future holders of the Bonds and coupons issued and to be issued thereunder, all the shares of stock of the Subsidiary
were released from the lien of the Original Indenture; and the Company became entitled to change the general designation of the Bonds so as to omit the words “and Collateral Trust”; and 

WHEREAS, the Articles of Incorporation of the Company were duly amended on April 23, 1956, to change its corporate name from
“Union Electric Company of Missouri” to “Union Electric Company”; and 
 WHEREAS, the Articles of Agreement of
the Trustee were duly amended effective on January 4, 1982 to change its corporate name from “St. Louis Union Trust Company” to “Centerre Trust Company of St. Louis”, and further amended on December 9, 1988, to change
its corporate name from “Centerre Trust Company of St. Louis” to “Boatmen’s Trust Company”; and 

  
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 WHEREAS, that on March 13, 1998, Boatmen’s Trust Company merged into
NationsBank, National Association and effective July 5, 1999, changed its name to Bank of America, National Association; and 

WHEREAS, that on February 1, 2000, The Bank of New York, as transferee of the corporate trust business of Bank of America,
National Association (formerly known as Boatmen’s Trust Company), Trustee under the Original Indenture, became successor Trustee under the Original Indenture; and 

WHEREAS, that effective as of July 1, 2008, The Bank of New York changed its name to The Bank of New York Mellon; and 

WHEREAS, the Company is entitled at this time to have authenticated and delivered additional Bonds on the basis of “property
additions” upon compliance with and pursuant to the provisions of Section 4 of Article III of the Original Indenture or on the basis of “refundable Bonds” upon compliance with and pursuant to the provisions of Section 6
of Article III of the Original Indenture; and 
 WHEREAS, the Company desires by this Supplemental Indenture to provide for the
creation of a new series of Bonds under the Original Indenture, to have the designation provided in Article I, Section 1 hereof (herein called the “New Bonds”), and the Original Indenture provides that certain terms and
provisions, as determined by the Board of Directors of the Company, of the Bonds of any particular series may be expressed in and provided by the execution of an appropriate supplemental indenture; and 

WHEREAS, the Original Indenture provides that the Company and the Trustee may enter into indentures supplemental to the Original
Indenture specifically to convey, transfer and assign to the Trustee and to subject to the lien of the Original Indenture additional properties acquired by the Company; and 

WHEREAS, the Company, in the exercise of the powers and authority conferred upon and reserved to it under the provisions of the
Original Indenture and pursuant to appropriate resolutions of the Board of Directors, has duly resolved and determined to make, execute and deliver to the Trustee a Supplemental Indenture in the form hereof for the purposes herein provided; and 

WHEREAS, all conditions and requirements necessary to make this Supplemental Indenture a valid, binding and legal instrument have been
done, performed and fulfilled and the execution and delivery hereof have been in all respects duly authorized; 
 NOW, THEREFORE, THIS
INDENTURE WITNESSETH: 
 That, in consideration of the premises and of the mutual covenants herein contained and of the acceptance of
this trust by the Trustee and of the sum of One Dollar duly paid by the Trustee to the Company at or before the time of the execution of this Supplemental Indenture, and of other valuable considerations, the receipt whereof is hereby acknowledged,
and in order further to secure the payment of the principal of and interest (and premium, if any) on all Bonds at any time issued and outstanding under the Original Indenture, according to their tenor and effect, the Company has executed and
delivered this Supplemental Indenture and has granted, bargained, sold, warranted, aliened, remised, released, conveyed, assigned, transferred, mortgaged, pledged, set over and confirmed and by these presents does grant, bargain, sell, warrant,
alien, remise, release, convey, assign, transfer, mortgage, pledge, set over and confirm unto The Bank of New York Mellon, as Trustee, and to its successors in trust under the Original Indenture forever, all and singular the following described
properties (in addition to all other properties heretofore subjected to the lien of the Original Indenture and not heretofore released from the lien thereof) - that is to say: 

  
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 FIRST. 

ALL (except as in the Original Indenture expressly excepted) power houses, plants, buildings and other structures, dams, dam
sites, substations, heating plants, gas works, holders and tanks, together with all and singular the electric, heating, gas and mechanical appliances appurtenant thereto of every nature whatsoever, now owned by the Company, including all and
singular the machinery, engines, boilers, furnaces, generators, dynamos, turbines and motors, and all and every character of mechanical appliance for generating or producing electricity, steam, gas and other agencies for light, heat, cold, or power
or other purposes, and all transmission and distribution systems used for the transmission and distribution of electricity, steam, gas and other agencies for light, heat, cold or power or any other purpose whatsoever, whether underground or
overhead, surface or otherwise, now owned by the Company, including all poles, towers, posts, wires, cables, conduits, manholes, mains, pipes, tubes, drains, furnaces, switchboards, transformers, conductors, insulators, supports, meters, lamps,
fuses, junction boxes, regulator stations, and other electric, steam and gas fixtures and apparatus; all of the aforementioned property being located in the City of St. Louis, the counties of Adair, Audrain, Benton, Bollinger, Boone, Butler,
Caldwell, Callaway, Camden, Cape Girardeau, Clark, Clay, Clinton, Cole, Cooper, Crawford, Daviess, Dunklin, Franklin, Gasconade, Howard, Iron, Jefferson, Knox, Lewis, Lincoln, Livingston, Macon, Madison, Maries, Marion, Miller, Mississippi,
Moniteau, Montgomery, Morgan, New Madrid, Osage, Pemiscot, Perry, Pettis, Phelps, Pike, Pulaski, Ralls, Randolph, Ray, Reynolds, Ripley, St. Charles, St. Francois, Ste. Genevieve, St. Louis, Saline, Schuyler, Scott, Stoddard, Warren, Washington, and
Wayne, Missouri, the counties of Clay, Hancock, Henderson, Madison, Marion, Perry, Piatt and St. Clair, Illinois, and the counties of Des Moines, Henry, Johnson, Lee, and Washington, Iowa, upon real estate owned by the Company, or occupied by
it under rights to so occupy, which real estate is described in, or added through the provisions of, the Indenture of Mortgage and Deed of Trust dated June 15, 1937, the Supplemental Indentures dated May 1, 1941, March 17, 1942,
April 13, 1945, April 27, 1945, October 1, 1945, April 11, 1947, April 13, 1949, September 13, 1950, December 1, 1950, September 20, 1951, May 1, 1952, March 1, 1954, May 1, 1955,
August 31, 1955, April 1, 1956, July 1, 1956, August 1, 1957, February 1, 1958, March 1, 1958, November 5, 1958, March 16, 1959, June 24, 1959, December 11, 1959, August 17, 1960,
September 1, 1960, October 24, 1960, June 30, 1961, July 1, 1961, August 9, 1962, September 30, 1963, November 1, 1963, March 12, 1965, April 1, 1965, April 14, 1966, May 1, 1966,
February 17, 1967, March 1, 1967, February 19, 1968, March 15, 1968, August 21, 1968, April 7, 1969, May 1, 1969, September 12, 1969, October 1, 1969, March 26, 1970, April 1, 1970,
June 12, 1970, January 1, 1971, April 1, 1971, September 15, 1971, December 3, 1973, February 1, 1974, April 25, 1974, February 3, 1975, March 1, 1975, June 11, 1975, May 12, 1976,
August 16, 1976, April 26, 1977, October 15, 1977, November 7, 1977, December 1, 1977, August 1, 1978, October 12, 1979, November 1, 1979, July 7, 1980, August 1, 1980, August 20, 1980,
February 1, 1981, October 8, 1981, August 27, 1982, September 1, 1982, December 15, 1982, March 1, 1983, June 21, 1984, December 12, 1984, June 11, 1985, March 1, 1986, May 1, 1986, May 1,
1990, December 1, 1991, December 4, 1991, January 1, 1992, September 30, 1992, October 1, 1992, December 1, 1992, February 1, 1993, February 18, 1993, May 1, 1993, August 1, 1993, October 1,
1993, January 1, 1994, February 1, 2000, August 15, 2002, March 5, 2003, April 1, 2003, July 15, 2003, October 1, 2003, February 1, 2004 (eight separate indentures supplemental thereto), May 1, 2004,
September 1, 2004, January 1, 2005, July 1, 2005, December 1, 2005, June 1, 2007, April 1, 2008, June 1, 2008, March 1, 2009, May 15, 2012, September 1, 2012, April 1, 2014, March 15, 2015,
June 1, 2017, April 1, 2018, March 1, 2019, September 15, 2019, March 1, 2020, and this Supplemental Indenture, or attached to or connected with such real estate or transmission or distribution systems of the Company leading
from or into such real estate. 
 SECOND. 

ALSO, (except as in the Original Indenture expressly excepted) all franchises and all permits, ordinances, easements, privileges,
immunities and licenses, all rights to construct, maintain and operate overhead, surface and underground systems for the distribution and transmission of electricity, steam, gas or other agencies for the supply to itself or others of light, heat,
cold or power, all rights-of-way, all waters, water rights and flowage rights and all grants and consents, now owned or, subject to the provisions of Article XII of
the Original Indenture, which it may hereafter acquire. 

  
 4 

 ALSO, (except as in the Original Indenture expressly excepted) all inventions, patent
rights and licenses of every kind now owned by the Company or, subject to the provisions of Article XII of the Original Indenture, which it may hereafter acquire. 

THIRD. 
 ALSO,
subject to the provisions of Article XII of the Original Indenture, all other property, real, personal and mixed (except as therein or herein expressly excepted) of every nature and kind and wheresoever situated now or hereafter possessed by or
belonging to the Company, or to which it is now, or may at any time hereafter be, in any manner entitled at law or in equity. 

EXPRESSLY EXCEPTING AND EXCLUDING, HOWEVER, from this Supplemental Indenture and from the lien and operation hereof: 

(a)    all property expressly excepted and excluded from the Original Indenture, and from the lien and operation thereof;
and 
 (b)    when the amendment set forth in Section 2 of Article III of the Supplemental Indenture dated
May 15, 2012 becomes effective, all Excepted Property as defined in such Section. 
 TO HAVE AND TO HOLD all said properties,
real, personal and mixed, mortgaged, pledged and conveyed by the Company as aforesaid, or intended so to be, unto the Trustee and its successors and assigns forever. 

SUBJECT, HOWEVER, to the exceptions and reservations and matters hereinabove recited, to existing leases, to existing liens upon rights
of way for transmission or distribution line purposes, as defined in Article I of the Original Indenture, and any extensions thereof, and subject to existing easements for streets, alleys, highways, rights-of-way and railroad purposes over, upon and across certain of the property hereinbefore described, and subject also to all the terms, conditions, agreements, covenants, exceptions and reservations
expressed or provided in the deeds or other instruments respectively under and by virtue of which the Company acquired the properties hereinabove described, and to undetermined liens and charges, if any, incidental to construction or other existing
permitted liens as defined in Article I of the Original Indenture. 
 IN TRUST, NEVERTHELESS, upon the terms and trusts in the
Original Indenture and the indentures supplemental thereto, including this Supplemental Indenture, set forth, for the equal and proportionate benefit and security of all present and future holders of the Bonds and coupons issued and to be issued
thereunder, or any of them, without preference of any of said Bonds and coupons of any particular series over the Bonds and coupons of any other series, by reason of priority in the time of the issue, sale or negotiation thereof, or by reason of the
purpose of issue or otherwise howsoever, except as otherwise provided in Section 2 of Article IV of the Original Indenture. 

AND IT IS HEREBY COVENANTED, DECLARED AND AGREED, by and between the parties hereto, for the benefit of those who shall hold the Bonds
and coupons, or any of them to be issued under the Original Indenture, as follows: 
 ARTICLE I 

DESCRIPTION OF THE NEW BONDS 

Section 1.    There is hereby created a new series of Bonds to be executed, authenticated and delivered under and
secured by the Original Indenture which shall, subject to the provisions of Section 1 of Article II of the Original Indenture, be designated as “2.625% First Mortgage Bonds due 2051” (the “New Bonds”) of the Company.
The New Bonds shall be executed, authenticated and delivered in accordance with the provisions of, and shall in all respects be subject to all of the terms, conditions and covenants of, the Original Indenture. 

  
 5 

 The New Bonds shall mature on March 15, 2051, and shall bear interest at the rate per
annum set forth in the form of the New Bond contained in Section 3 of this Article I, payable semi-annually in arrears on the 15th day of March and the 15th day of September in each year (each, an “Interest Payment Date”),
commencing on March 15, 2021, and at maturity. The New Bonds shall be payable as to principal and interest in any coin or currency of the United States of America which at the time of payment is legal tender for public and private debts,
and shall be payable, in immediately available funds, at the office of the Trustee. 
 Section 2.    The New Bonds
will be initially issued in global form registered in the name of CEDE & CO. (as nominee for The Depository Trust Company). The New Bonds will bear the depository legend in substantially the form set forth in Section 3 of this
Article I. Any transfer shall be effected at the principal office or place of business of the Trustee. The New Bonds are exchangeable for the New Bonds of other denominations, as in the Original Indenture provided, except that payment of a
service charge therefor will not be required by the Company. 
 Notwithstanding the provisions of Section 6 of Article II of the
Original Indenture, the New Bonds shall be dated the date of authentication and shall bear interest from the Interest Payment Date to which interest on the New Bonds has been paid next preceding the date thereof, unless such date is an Interest
Payment Date to which interest has been paid, in which case they shall bear interest from the date thereof, or unless the date thereof is prior to March 15, 2021, in which case they shall bear interest from October 9, 2020; provided,
however, that, subject to the provisions of this Section with respect to failure by the Company to pay any interest on an Interest Payment Date, the holder of any New Bond dated after a record date (as hereinafter defined) for the payment of
interest and prior to the date of payment of such interest shall not be entitled to payment of such interest and shall have no claim against the Company with respect thereto. 

The person in whose name any New Bond is registered at the close of business on any record date with respect to any Interest Payment Date
shall be entitled to receive the interest payable on such Interest Payment Date notwithstanding the cancellation of such Bond upon any transfer or exchange thereof subsequent to the record date and prior to such Interest Payment Date, except if and
to the extent the Company shall default in the payment of the interest due on such Interest Payment Date, in which case such defaulted interest shall be paid to the person in whose name such Bond is registered on the date of payment of such
defaulted interest or on a subsequent record date for such payment if one shall have been established as hereinafter provided. A subsequent record date may be established by the Company by notice mailed to the holders of the New Bonds not less than
ten days preceding such record date, which record date shall be not more than thirty days prior to the subsequent Interest Payment Date. The term “record date” as used in this Section with respect to any regular interest payment
date shall mean the March 1 or September 1, as the case may be, next preceding such Interest Payment Date, or, if such March 1 or September 1 shall be a legal holiday in the State of New York or in the State of Missouri or a day
on which banking institutions in the Borough of Manhattan, The City of New York, or the City of St. Louis, Missouri, are authorized by law to close, the next preceding day which shall not be a legal holiday or a day on which such institutions are so
authorized to close. 

  
 6 

 Section 3.    The New Bonds and the Trustee’s certificate on
the New Bonds shall be substantially in the following forms respectively: 
 [FORM OF FACE OF NEW BOND] 

 

			
	REGISTERED	  	REGISTERED

 [DTC Legend 

THIS BOND IS A GLOBAL BOND REGISTERED IN THE NAME OF THE DEPOSITARY (REFERRED TO HEREIN) OR A NOMINEE THEREOF AND, UNLESS AND UNTIL IT IS
EXCHANGED IN WHOLE FOR THE INDIVIDUAL BONDS REPRESENTED HEREBY AS PROVIDED IN THE AMENDED INDENTURE REFERRED TO BELOW, THIS BOND MAY NOT BE TRANSFERRED EXCEPT AS A WHOLE BY THE DEPOSITARY TO A NOMINEE OF THE DEPOSITARY OR BY A NOMINEE OF THE
DEPOSITARY TO THE DEPOSITARY OR ANOTHER NOMINEE OF THE DEPOSITARY OR BY THE DEPOSITARY OR ANY SUCH NOMINEE TO A SUCCESSOR DEPOSITARY OR A NOMINEE OF SUCH SUCCESSOR DEPOSITARY. UNLESS THIS BOND IS PRESENTED BY AN AUTHORIZED REPRESENTATIVE OF THE
DEPOSITORY TRUST COMPANY (55 WATER STREET, NEW YORK, NEW YORK), TO THE TRUSTEE FOR REGISTRATION OF TRANSFER, EXCHANGE OR PAYMENT, AND ANY CERTIFICATE ISSUED IS REGISTERED IN THE NAME OF CEDE & CO. OR SUCH OTHER NAME AS REQUESTED BY AN
AUTHORIZED REPRESENTATIVE OF THE DEPOSITORY TRUST COMPANY AND ANY PAYMENT IS MADE TO CEDE & CO., ANY TRANSFER, PLEDGE OR OTHER USE HEREOF FOR VALUE OR OTHERWISE BY OR TO ANY PERSON IS WRONGFUL SINCE THE REGISTERED OWNER HEREOF,
CEDE & CO., HAS AN INTEREST HEREIN.] 
 UNION ELECTRIC COMPANY 

(Incorporated under the laws of the State of Missouri) 

2.625% FIRST MORTGAGE BOND DUE 2051 
  

					
	CUSIP:	  	NUMBER:	  	
	ISIN:	  		  	
			
	ORIGINAL ISSUE DATE:	  	PRINCIPAL AMOUNT: $	  	
			
	INTEREST RATE: 2.625%	  	MATURITY DATE: March 15, 2051	  	

 UNION ELECTRIC COMPANY, a corporation organized and existing under the laws of the State of Missouri
(hereinafter called the “Company”, which term shall include any successor corporation as defined in the Amended Indenture referred to on the reverse hereof), for value received, hereby promises to pay to
                                , or registered assigns, the sum of
                                         
                        Dollars
($                    ), on the Maturity Date set forth above in any coin or currency of the United States of America which at the time of
payment is legal tender for public and private debts, and to pay interest thereon, in like coin or currency, at the Interest Rate set forth above, payable semi-annually in arrears, on March 15 and September 15 in each year (each, an
“Interest Payment Date”) until the Maturity Date, commencing March 15, 2021, and on the Maturity Date or, if the Company shall default in the payment of the principal hereof, until the Company’s obligation with respect to the
payment of such principal shall be discharged as provided in the Amended Indenture referred to on the reverse hereof. Such interest shall be payable from the March 15 or September 15, as the case may be, next preceding the date hereof to
which interest has not been paid, unless the date hereof is a March 15 or September 15 to which interest has been paid, in which case from the date hereof, or unless the date hereof is prior to the first payment of interest, in which case
from the Original Issue Date set forth above. The interest so payable will be paid to the person in whose name this Bond, or the Bond in exchange or substitution for which this Bond shall have been issued, shall have been registered at the close of
business on the March 1 or September 1, as the case may be (each, a “Record Date”), next preceding the date of payment, subject to certain exceptions set forth in the Amended Indenture. The principal of, premium, if any, and
interest on, this Bond are payable, in immediately 

  
 7 

 
available funds, at the office of the Trustee hereinafter referred to; provided, however, that at the option of the Company, interest on this Bond may be paid by check mailed to the registered
holder of this Bond at such holder’s address as it shall appear on the books of the Company to be kept for that purpose or by a wire transfer to an account designated by the registered holder of this Bond entitled thereto. 

This Bond shall not be entitled to any benefit under the Amended Indenture or any indenture supplemental thereto, or become valid or
obligatory for any purpose, until The Bank of New York Mellon, the Trustee under the Amended Indenture, or a successor trustee thereto under the Amended Indenture, or an agent therefor, shall have signed the form of certificate endorsed hereon. 

The provisions of this Bond are continued on the reverse hereof and such continued provisions shall for all purposes have the same effect as
though fully set forth at this place. 

  
 8 

 IN WITNESS WHEREOF, Union Electric Company has caused this Bond to be signed in its name by
its Chairman of the Board or President or a Vice President by manual signature or a facsimile thereof, and its corporate seal (or a facsimile thereof) to be hereto affixed and attested by its Secretary or an Assistant Secretary by manual signature
or a facsimile thereof. 
 Dated 
  

			
	UNION ELECTRIC COMPANY

 
			
		
	By	 	  

 

							
	[CORPORATE SEAL]	 		 		 	
				
	Attest:	 		 		 	
	  
	 		 		 	

 [FORM OF TRUSTEE’S CERTIFICATE] 

This Bond is one of the Bonds, of the series designated therein, described in the within-mentioned Amended Indenture and Supplemental
Indenture of October 1, 2020. 
  

			
	THE BANK OF NEW YORK MELLON, as
	TRUSTEE

 
			
		
	By	 	  

 
			
	 Authorized Officer

  
 9 

 [FORM OF REVERSE OF NEW BOND] 

This Bond is one of a duly authorized issue of Bonds of the Company (herein called the “Bonds”), in unlimited aggregate principal
amount, of the series hereinafter specified, all issued and to be issued under and equally secured by the Indenture of Mortgage and Deed of Trust, dated June 15, 1937, executed by the Company to The Bank of New York Mellon, formerly The Bank of
New York (successor trustee to Bank of America, National Association, formerly Boatmen’s Trust Company), as trustee (herein called the “Trustee”), as amended by indentures supplemental thereto dated May 1, 1941, April 1,
1971, February 1, 1974, July 7, 1980, February 1, 2000, August 15, 2002 and May 15, 2012, between the Company and the Trustee (said mortgage and deed of trust, as so amended, being herein called the “Amended
Indenture”), to which Amended Indenture and all indentures supplemental thereto reference is hereby made for a description of the properties mortgaged and pledged, the nature and extent of the security, the rights of the bearers or registered
owners of the Bonds and of the Trustee in respect thereto, and the terms and conditions upon which the Bonds are, and are to be, secured. To the extent permitted by, and as provided in, the Amended Indenture, modifications or alterations of the
Amended Indenture, or of any indenture supplemental thereto, and of the rights and obligations of the Company and of the holders of the Bonds may be made with the consent of the Company by an affirmative vote or consent of the holders of the Bonds
then outstanding as are specified in the Amended Indenture. No such modification or alteration shall be made which will affect the terms of payment of the principal of, or interest or premium on, this Bond, which are unconditional. The Bonds may be
issued in series, for various principal sums, may mature at different times, may bear interest at different rates and may otherwise vary as in the Amended Indenture provided. This Bond is one of a series designated as the “2.625% First Mortgage
Bonds due 2051” (herein called the “Bonds of this Series”) of the Company, issued under and secured by the Amended Indenture and described in the indenture (hereinafter called the “New Supplemental Indenture”) dated
October 1, 2020, between the Company and the Trustee, supplemental to the Amended Indenture. 
 The Bonds of this Series are not
entitled to the benefit of any improvement, maintenance or analogous fund. 
 All or a portion of the Bonds of this Series may be
redeemed at the option of the Company at any time or from time to time. The redemption price for the Bonds of this Series to be redeemed on any redemption date prior to September 15, 2050 (six months prior to the Maturity Date) (the
“Par Call Date”) will be equal to the greater of the following amounts: (a) 100% of the principal amount of the Bonds of this Series being redeemed on that redemption date; or (b) the sum of the present values of the remaining
scheduled payments of principal and interest on the Bonds of this Series being redeemed on that redemption date that would be payable if such Bonds matured on the Par Call Date (not including any portion of any payments of interest accrued to the
redemption date) discounted to the redemption date on a semiannual basis (assuming a 360 day year consisting of twelve 30 day months) at the Adjusted Treasury Rate (as defined below), plus 20 basis points, as determined by the Reference
Treasury Dealer (as defined below), plus, in each case, accrued and unpaid interest thereon to the redemption date. The redemption price for the Bonds of this Series to be redeemed on any redemption date on or after the Par Call Date will be equal
to 100% of the principal amount of the Bonds of this Series being redeemed on that redemption date plus accrued and unpaid interest thereon to the redemption date. Notwithstanding the foregoing, installments of interest on Bonds of this
Series that are due and payable on Interest Payment Dates falling on or prior to a redemption date will be payable on the Interest Payment Date to the holder of this Bond as of the close of business on the relevant Record Date. 

With respect to a redemption occurring prior to the Par Call Date, the Company shall give the Trustee written notice of the redemption price
promptly after the calculation thereof and the Trustee shall not be responsible for such calculation. 
 The Company shall send notice of
any redemption at least 10 days but not more than 60 days before the redemption date to each holder of the Bonds of this Series to be redeemed, and, if less than all Bonds of this Series are to be redeemed, the particular Bonds of
this Series to be redeemed will be selected by the Trustee by lot; provided that as long as the Bonds of this Series are represented by global certificates registered in the name of The Depository Trust Company, or its nominee, beneficial interests
in such global certificates will be selected for redemption by The Depository Trust Company in accordance with its standard procedures therefor. Unless the Company defaults in payment of the redemption price, on and after the redemption date,
interest will cease to accrue on the Bonds of this Series or portions thereof called for redemption. 

  
 10 

 Any notice of redemption at the Company’s option may state that such redemption will be
conditional upon receipt by the Trustee, on or prior to the redemption date, of money sufficient to pay the principal of and premium, if any, and interest on, the Bonds of this Series or portions thereof called for redemption, and that if such money
has not been so received, such notice will be of no force and effect and the Company will not be required to redeem such Bonds or portions thereof. 

“ADJUSTED TREASURY RATE” means, with respect to any redemption date, the rate per annum equal to the semiannual equivalent yield to
maturity of the Comparable Treasury Issue, assuming a price for the Comparable Treasury Issue (expressed as a percentage of its principal amount) equal to the Comparable Treasury Price for such redemption date. 

“COMPARABLE TREASURY ISSUE” means the United States Treasury security selected by the Reference Treasury Dealer as having a maturity
comparable to the remaining term of the Bonds of this Series to be redeemed (assuming, for this purpose, that the Bonds matured on the Par Call Date) that would be utilized, at the time of selection and in accordance with customary financial
practice, in pricing new issues of corporate debt securities of comparable maturity to the Par Call Date. 
 “COMPARABLE TREASURY
PRICE” means, with respect to any redemption date, (A) the average of the Reference Treasury Dealer Quotations for such redemption date, after excluding the highest and lowest of such Reference Treasury Dealer Quotations, or (B) if
the Company obtains fewer than four such Reference Treasury Dealer Quotations, the average of all such quotations, or (C) if only one Reference Treasury Dealer Quotation is received, such quotation. 

“REFERENCE TREASURY DEALER” means each of (A) Barclays Capital Inc., BofA Securities, Inc. and RBC Capital Markets, LLC, or, in
each case, an affiliate thereof, which are primary U.S. Government securities dealers in the United States (each, a “Primary Treasury Dealer”), and their respective successors; provided, however, that if any of the foregoing shall cease to
be a Primary Treasury Dealer, the Company will substitute therefor another Primary Treasury Dealer; and (B) any other Primary Treasury Dealer(s) selected by the Company. 

“REFERENCE TREASURY DEALER QUOTATIONS” means, with respect to each Reference Treasury Dealer and any redemption date, the average,
as determined by the Company, of the bid and asked prices for the Comparable Treasury Issue (expressed in each case as a percentage of its principal amount) quoted in writing to the Company by such Reference Treasury Dealer at 5:00 p.m. (New
York City time) on the third Business Day preceding such redemption date. 
 In case an event of default, as defined in the Amended
Indenture, shall occur, the principal of all the Bonds at any such time outstanding under the Amended Indenture may be declared or may become due and payable, upon the conditions and in the manner and with the effect provided in the Amended
Indenture. The Amended Indenture provides that such declaration may in certain events be waived by the holders of a majority in principal amount of the Bonds outstanding. 

This Bond is exchangeable by the registered owner hereof, in person or by duly authorized attorney, on the books of the Company to be kept for
that purpose at the office of the Company in the City of St. Louis, Missouri, upon surrender and cancellation of this Bond and on presentation of a duly executed written instrument of transfer, and thereupon a new Bond or Bonds of the same
series, of the same aggregate principal amount and in authorized denominations will be issued to the transferee or transferees in exchange herefor, without payment of any charge other than stamp taxes and other governmental charges incident thereto;
and this Bond with or without others of like series, may in like manner be exchanged for one or more new Bonds of the same series of other authorized denominations but of the same aggregate principal amount; all subject to the terms and conditions
set forth in the Amended Indenture. 

  
 11 

 Each initial and future holder of this Bond, by its acquisition of an interest in this Bond,
irrevocably (a) consents to the amendments set forth in Article III of the Supplemental Indenture dated as of May 15, 2012, supplemental to the Amended Indenture, without any other or further action by any holder of this Bond, and
(b) designates the Trustee, and its successors, as its proxy with irrevocable instructions to vote and deliver written consents on behalf of such holder in favor of such amendments at any meeting of holders, in lieu of any meeting of holders,
in response to any consent solicitation or otherwise. 
 No recourse shall be had for the payment of the principal of, premium, if any, or
the interest on, this Bond, or for any claim based hereon or on the Amended Indenture or any indenture supplemental thereto, against any incorporator, or against any stockholder, director or officer, past, present or future, of the Company, or of
any predecessor or successor corporation, either directly or through the Company or any such predecessor or successor corporation, whether for amounts unpaid on stock subscriptions or by virtue of any constitution, statute or rule of law, or by the
enforcement of any assessment or penalty or otherwise, all such liability, whether at common law, in equity, by any constitution, statute or otherwise, of incorporators, stockholders, directors or officers being released by every owner hereof by the
acceptance of this Bond and as part of the consideration for the issue hereof, and being likewise released by the terms of the Amended Indenture. 

[END OF FORM OF REVERSE OF NEW BOND] 

Section 4.    Until New Bonds in definitive form are ready for delivery, the Company may execute, and upon its
request in writing the Trustee shall authenticate and deliver, in lieu thereof, New Bonds in temporary form, as provided in Section 9 of Article II of the Original Indenture. 

ARTICLE II 
 ISSUE OF THE NEW
BONDS 
 Section 1.    The principal amount of the New Bonds which may be authenticated and delivered hereunder
is not limited. 
 Section 2.    The New Bonds in the aggregate principal amount of Five Hundred Fifty Million
Dollars ($550,000,000), being the initial issue of the New Bonds, may forthwith at any time or from time to time be executed by the Company and delivered to the Trustee and shall be authenticated by the Trustee and delivered (either before or after
the filing or recording hereof) to or upon the order of the Company, upon compliance by the Company with the applicable provisions of Article III and Article XVIII of the Original Indenture. 

Section 3.    After the authentication of the New Bonds, without the consent of any existing holder of the New Bonds,
the Company may thereafter obtain from time to time the authentication of additional New Bonds pursuant to the terms of the Original Indenture by the order of the Company referring to this Supplemental Indenture having the same terms and conditions
as the Outstanding New Bonds in all respects (including the same CUSIP number), except for the date of original issuance, the offering price and, if applicable, the initial interest accrual date and the initial Interest Payment Date. 

ARTICLE III 
 REDEMPTION OF THE
NEW BONDS AND CONSENT TO AMENDMENTS 
 Section 1.    The New Bonds are redeemable as set forth in the form of
such Bonds set forth in Section 3 of Article I hereof. If the Company elects to redeem any New Bonds, it shall notify the Trustee of the redemption date and the principal amount of such Bonds to be redeemed not less than 15 days nor more
than 90 days before such redemption date. 
 Section 2.    Each initial and future holder of the New Bonds, by its
acquisition of an interest in such Bonds, irrevocably (a) consents to the amendments set forth in Article III of the Supplemental Indenture dated as of May 15, 2012, supplemental to the Original Indenture, without any other or further
action by any holder of such 

  
 12 

 
bonds, and (b) designates the Trustee, and its successors, as its proxy with irrevocable instructions to vote and deliver written consents on behalf of such holder in favor of such
amendments at any meeting of holders, in lieu of any meeting of holders, in response to any consent solicitation or otherwise. 
 ARTICLE IV

 COVENANTS 
 The
Company hereby covenants, warrants and agrees: 
 Section 1.    That the Company is lawfully seized and possessed
of all of the mortgaged property described in the granting clauses of this Supplemental Indenture to the extent shown on its books and records as of the date hereof; that it has good right and lawful authority to mortgage the same as provided in
this Supplemental Indenture; and that such mortgaged property will be, at the actual date of the issue of the New Bonds, free and clear of any deed of trust, mortgage, lien, charge or encumbrance thereon or affecting the title thereto prior to the
lien of the Original Indenture, except for permitted liens and as set forth in the granting clauses of the Original Indenture and this Supplemental Indenture. 

ARTICLE V 
 THE TRUSTEE

 The Trustee hereby accepts the trusts hereby declared and provided, and agrees to perform the same upon the terms and conditions in
the Original Indenture and in this Supplemental Indenture set forth, and upon the following terms and conditions: 
 The Trustee shall not
be responsible in any manner whatsoever for or in respect of the validity or sufficiency of this Supplemental Indenture or the due execution hereof by the Company or for or in respect of the recitals contained herein, all of which recitals are made
by the Company solely. 
 ARTICLE VI 

MISCELLANEOUS PROVISIONS. 

Section 1.    Except as otherwise defined herein, all terms contained in this Supplemental Indenture shall, for all
purposes thereof, have the meanings given to such terms in Article I of the Original Indenture. 

Section 2.    This Supplemental Indenture may be simultaneously executed in any number of counterparts, each of which
when so executed shall be deemed to be an original; but such counterparts shall together constitute but one and the same instrument. 

  
 13 

 IN WITNESS WHEREOF, said Union Electric Company has caused this Supplemental
Indenture to be executed on its behalf by its Chairman of the Board or President or one of its Vice Presidents and this Supplemental Indenture to be attested by its Secretary or one of its Assistant Secretaries; and said The Bank of New York Mellon,
in evidence of its acceptance of the trust hereby created, has caused this Supplemental Indenture to be executed on its behalf by its President or one of its Vice Presidents, and this Supplemental Indenture to be attested by one of its Vice
Presidents, its Secretary, or one of its Assistant Secretaries; all as of the 1st day of October, Two thousand and twenty. 
  

									
	Attested:	 		  	UNION ELECTRIC COMPANY,	 	
		 		  	    1901 Chouteau Avenue 
    St. Louis, Missouri 63103	 	
					
	     /s/ Craig W. Stensland
	 		  	By:	 	     /s/ Darryl T. Sagel
	 	
	      Craig W. Stensland	 		  	Name:    Darryl T. Sagel	 	
	      Assistant Secretary	 		  	Title:      Vice President and Treasurer	 	

									
	Attested:	 		  	THE BANK OF NEW YORK MELLON	 	
					
	     /s/ Quintanna L. Walker
	 		  	By:	 	     /s/ Christine S. Conway
	 	
	 Name: Quintanna L. Walker
 Title:
  Vice President
	 		  	 Name:    Christine S. Conway

Title:      Vice President
	 	

			
	 STATE OF MISSOURI
	  	 }

		  	 } SS.:

	 CITY OF ST. LOUIS
	  	 }

 On this 1st day of October, 2020, before me appeared Darryl T. Sagel and Craig W. Stensland, to me personally
known, who, being by me duly sworn, did say that they are the Vice President and Treasurer, and an Assistant Secretary of UNION ELECTRIC COMPANY, a corporation, and that said instrument was signed on behalf of said corporation by authority of
its Board of Directors, and said Vice President and Treasurer, and Assistant Secretary acknowledged said instrument to be the free act and deed of said corporation. 

IN TESTIMONY WHEREOF, I have hereto set my hand and affixed my official seal at my office, in the City and State aforesaid, the day and
year last above written. 
  

	
	     /s/ Kelly J. Roth

	 Notary Public – Notary Seal

	 State of Missouri

	 Commissioned for St. Charles County

	 My Commission Expires: May 12, 2022

	 Commission Number: 14440245

			
	 STATE OF NEW YORK
	  	 }

		  	 } SS.:

	 COUNTY OF NEW YORK
	  	 }

 On this 2nd day of October, 2020, before me appeared Christine S. Conway, to me personally known, who, being
by me duly sworn, did say that she is a Vice President of THE BANK OF NEW YORK MELLON, a corporation, and that said instrument was signed on behalf of said corporation, as the trustee thereunder by authority of its Board of Directors, and
said Vice President, acknowledged said instrument to be the free act and deed of said corporation as the trustee under said instrument. 

IN TESTIMONY WHEREOF, I have hereto set my hand and affixed my official seal at my office, in the City and State aforesaid, the day and
year last above written. 
  

	
	 /s/ Helen Choi

	 Helen Choi

Notary Public, State of New York

No. 01CH6291290

Qualified in New York County

Commission Expires October 15, 2021Exhibit 10.13

 

SERVICES AGREEMENT

 

This Services Agreement
(this “Agreement”) is made and entered into as of July 15, 2020, (the “Effective Date”),
by and between Worldwide Clinical Trials, Inc., with offices at 3800 Paramount Parkway, Suite 400, 27560, Morrisville, NC, United
States, (together with its Affiliates, “Worldwide) and Neurotrope Bioscience, Inc., with offices at 1185 Avenue of
the Americas, 3rd Floor, New York, NY 10036 (“Sponsor”). Worldwide and Sponsor are sometimes individually referred
to herein as a “Party” and collectively as the “Parties”.

 

For purposes of this
Agreement, “Affiliates” means any entity that controls, is controlled by or is under common control with, that
Party. “Control” means the possession, directly or indirectly, of at least 50% of the share capital or voting
rights or of the power to direct or cause the direction of the management and policies of an entity, whether through the ownership
of voting securities, by contract or otherwise.

 

WHEREAS, Sponsor is
engaged in the research and development of pharmaceutical products;

 

WHEREAS, Worldwide
is engaged in providing services to pharmaceutical manufacturers in support of their clinical research and product development
activities;

 

WHEREAS, Worldwide
and Sponsor desire that Worldwide provide certain services with respect to Sponsor’s clinical study, NTRP-101-204 entitled
“A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Assessing Safety, Tolerability and Long-term Efficacy of Bryostatin
in the Treatment of Moderately Severe Alzheimer’s Disease Subjects Not Receiving Memantine Treatment” (the "Study")
for the study of Sponsor’s drug Bryostatin 1 ("Study Drug"); and

 

WHEREAS, Sponsor and
Worldwide desire to enter into this Agreement in order to set forth definitively their respective rights and obligations with respect
to the conduct of the Study.

 

NOW THEREFORE, in consideration
of the premises and the mutual promises and undertakings herein contained, the receipt and sufficiency of which is hereby acknowledged,
the Parties agree as follows:

 

1.0       
SERVICES

  

Worldwide, itself or through one of its
Affiliates (if applicable) hereby agrees to perform the services (the “Services”) in accordance with the terms
of the scope of Services attached hereto as Exhibit A, incorporated herein by reference (the “Scope of Services”),
and this Agreement.

 

1.1       Performance

 

Worldwide shall perform the Services and
shall use its commercially reasonable efforts to complete the Services within the estimated time frame as set forth in the timeline
attached hereto as Exhibit B and incorporated herein by reference (“Timeline”). Such time estimate assumes,
however, the full cooperation of Sponsor, Regulatory Authorities, Ethics Committees and investigators and other third parties not
under Worldwide’s control, and shall be subject to adjustment (including costs) if the work for the Services is delayed due
to circumstances outside the reasonable control of Worldwide, including, but not limited to:

 

    Page 1 of 47

     

    

 

		·	failure of Sponsor to deliver clinical
supplies in due time, provided such failure is the actual cause of the delay; 
	 	 	 
		·	amendments to previously agreed upon protocols,
procedures or documents required for the Services at the request of Sponsor or Sponsor’s (or its advisors’); 
	 	 	 
		·	significant delays in pre-Study meetings
or in other tasks to be performed by Worldwide caused by Sponsor;
	 	 	 
		·	delays in obtaining or subsequent withdrawal
of regulatory or ethical review approvals concerning the Services; 
	 	 	 
		·	death or disability of any investigator
or other research specialist on the Study; 
	 	 	 
		·	higher ratio of drop-outs among trial
subjects than anticipated in this Agreement; 
	 	 	 
		·	lower enrollment rates than expected and
agreed to by Worldwide and Sponsor; or
	 	 	 
		·	unforeseen changes in the relevant medical
practice.

 

1.2       Compliance
with Laws/Agreements

 

Worldwide shall perform Services under
this Agreement in accordance with the terms of this Agreement, the Protocol for the Study, the Sponsor approved standard operating
procedures for the Study (the “Standard Operating Procedures”), the current Guidelines for Good Clinical Practice
promulgated by the FDA ("GCP Guidelines"), the Declaration of Helsinki of the 41st World Medical Assembly, South
Africa 1996 as amended, and all other applicable laws and regulations, including the following as applicable, 21 CFR Part 11, 312,
50, 54, 56, the Health Information Portability and Accountability Act of 1996 and all regulations and official guidelines promulgated
thereunder and the Health Information Technology for Economic and Clinical Health Act (the “Applicable Laws”).

 

The Parties and their respective owners,
officers, directors, employees or agents have not and shall not pay, give, offer or promise to pay or give, or authorize the payment,
directly or indirectly, of any money or anything of value to any foreign government official or employee (including employees of
state-owned institutions), for the purpose of (i) influencing any act or decision of such official or of such government, (ii)
inducing that person to do or omit doing any act in violation of his or her lawful duty, (iii) securing an improper advantage,
or (iv) influencing such official to use his influence with the government to effect or influence the decision of such government,
in order to assist Sponsor or Worldwide in obtaining or retaining business for or with or directing business to any person.

 

Each Party agrees to comply with all applicable
anticorruption laws, rules and regulations. The Parties agree to reasonably cooperate with each other’s diligence efforts
in order to satisfy each Party’s obligations under the United States Foreign Corrupt Practices Act, as amended (“FCPA”),
the UK Bribery Act and any implementing legislation under the OECD Convention Against Bribery of Foreign Government Officials in
International Business Transactions.

 

1.3        Transfer
of Obligations

 

Pursuant to Title 21 CFR Part 312.52, Sponsor
hereby transfers to Worldwide all of the obligations identified in Exhibit A attached hereto and incorporated by reference herein.
Notwithstanding the foregoing, Sponsor will retain the ultimate authority and control over and responsibility for the Study. The
Parties acknowledge and agree that Sponsor shall at all times be deemed to be the “sponsor” of the Study pursuant to
the terms of the Federal Food, Drug and Cosmetic Act, as from time to time amended, and the regulations of the U.S. Food and Drug
Administration (“FDA”), as promulgated in Title 21 of U.S. Code of Federal Regulations.

 

    Page 2 of 47

     

    

 

1.4       Changes

 

The Parties may make changes in or additions
to the Scope of Services, provided, however, that, subject to the terms of this Section 1.4, no such changes or additions shall
be implemented prior to the execution by the Parties of a change order (a “Change Order”), the form of which
is attached hereto and incorporated herein as Exhibit E. The Change Order shall include detailed information on the changes to
the Scope of Services and any associated changes to the Timeline, Budget and/or payment schedule. Sponsor acknowledges that Worldwide
is not obligated to perform any out-of-scope work described in a Change Order until the Change Order is signed by both Parties.
Provided, however, in the event that Worldwide provides additional Services or expends additional resources, at Sponsor’s
written request and in strict accordance with Sponsor’s written requirements, in the absence of a Change Order, Sponsor will
compensate and/or reimburse Worldwide for all pre-approved reasonable and necessary fees and reasonable and necessary out-of-pocket
costs actually incurred. For any Change Order that affects the scope of the regulatory obligations that have been transferred to
Worldwide, Worldwide and Sponsor shall execute a corresponding amendment to Exhibit A. Sponsor shall file such amendment where
appropriate, or as required by applicable law.

 

2.0       WORK
PRODUCT

 

During the term of this Agreement, Worldwide
shall maintain all materials and all other data or documents included in the Trial Master File obtained or generated by Worldwide
in the course of providing the relevant Services in accordance with Worldwide’s standard operating procedures, including
all computerized records and files (“Work Product”), in a secure area reasonably protected from fire, theft
and destruction with duplicate copies retained with the same care as the original Work Product. All Work Product shall be the Confidential
Information and the exclusive property of Sponsor. At the expiration or termination of this Agreement, and subject to satisfaction
of the Parties’ obligations thereunder, Sponsor shall provide Worldwide with written instructions as to the disposition of
the Work Product created under this Agreement. Such written instructions will provide that Worldwide (a) deliver the Work Product,
in the form in which Worldwide currently holds them, to a designated Sponsor location or to such other entity or at such other
address as Sponsor may specify, (b) retain the materials for the period of time specified in this Agreement, or (c) destroy all
such materials except for those which Worldwide is required by law or regulation to store or maintain. Upon expiration or termination
of this Agreement, any storage, destruction or shipping costs or services relating to such disposition of the Work Product will
be billed by Worldwide to Sponsor as Pass-through Expenses (as defined below) in accordance with the terms of this Agreement. Notwithstanding
the foregoing, Worldwide may retain one electronic archival backup copy of such Work Product in accordance with Worldwide’s
Data Retention Policy, subject to its ongoing obligation to maintain the confidentiality of such materials.

 

3.0        PAYMENT
AND COMPENSATION

 

The Parties agree that the fees and other
reimbursements that Worldwide will receive for performing the Services hereunder are subject to the following terms and conditions.

 

3.1        Compensation
for Services

 

This Agreement includes a budget for
the Services (the, “Budget”) to be performed by Worldwide, which is attached hereto as Exhibit C, and is
incorporated herein by reference. Sponsor shall pay to Worldwide such amounts as set forth and more fully described in the
Budget until such time as Worldwide and Sponsor agree that the Sponsor’s monetary obligations to Worldwide are fully
satisfied. Worldwide agrees that it shall not incur any cost or expense in excess of the amounts set forth in the Budget for
any item, without the prior written approval of Sponsor (in accordance with Section 1.4). Worldwide will use its commercially
reasonable efforts to control and limit the costs and expenses, including Pass-through Expenses (as defined below),
associated with this Agreement and to obtain and pass along to Sponsor all available discounts and allowances.

 

    Page 3 of 47

     

    

 

3.2       Pass-through
Expenses

 

Sponsor will reimburse Worldwide for travel
and other reasonable and necessary out-of-pocket expenses, exclusive of grant payments (described below), actually incurred by
Worldwide as agreed to by Sponsor and identified in the Budget or otherwise pre-approved in writing by the Sponsor, which Worldwide
will invoice to Sponsor without mark-up (“Pass-through Expenses”). All reimbursement of Pass-through Expenses
hereunder must be supported by receipts provided by Worldwide. Pass-through Expenses may include, but shall not be limited to lodging,
travel, third party vendor costs, and other reasonable and necessary costs.

 

In order to facilitate payment of invoices
for Worldwide’s pre-approved travel expenses incurred during the performance of Services, Worldwide will submit to Sponsor
a report containing at least the following details: (i) photocopies of receipts greater than Two Hundred Fifty ($250.00) USD for
Study-related travel expenses, including lodging, air travel, ground transportation, meals and other miscellaneous expenses, such
as overnight courier charges and photocopying, (ii) date and travel destination, (iii) employee name, and (iv) purpose of trip/expense.
In addition to copies of all receipts over Two Hundred Fifty ($250.00) USD, Sponsor shall have the right to obtain additional backing
documentation for any line item which requires further clarifications. Such requests shall be made in good faith and where there
is a specific concern with the line item(s) in question. All expenses, discounts, rebates and allowances obtained under Section
3.2 will be passed through and properly reflected in invoices to Sponsor and shall be without mark up. Worldwide will use economy
class airfare for all domestic flights and all international flights which are less than eight (8) hours in flight duration, and
business class airfare for all international fights which are eight (8) hours or more in flight duration. For the avoidance of
doubt, calculations of flight duration should not include layover time between flights.

 

3.3       Invoices;

 

Worldwide shall submit a reasonably detailed
invoice by email to Sponsor (rweinstein@neurotropebioscience.com) on a monthly basis in accordance with the Payment Schedule with
appropriate supporting documentation, including those set forth in Section 3.2.

 

3.4       Payment
Terms

 

Sponsor agrees to pay for Services and
Pass-through Expenses in accordance with the Payment Schedule, the (“Payment Schedule”) attached hereto as Exhibit
D and incorporated herein by reference. Sponsor will pay for all Services, Pass-through Expenses and other invoiced items within
forty five (45) days of receipt of invoice. All payments will be made in the currency noted in the Payment Schedule. All fees for
Services and Pass-through Expenses under this Agreement are stated exclusive of any local, state, federal or foreign sales and
use taxes, VAT, if any, as any such taxes shall be paid by Sponsor. If such taxes are applicable under local regulations, Worldwide
will add these taxes to the invoices at the relevant rate. For the avoidance of doubt, the requirements of this provision shall
not apply to any employment-related taxes, income taxes, duties, or withholding and shall only apply to taxes applicable to the
Services.

 

Payments shall be made by Sponsor via wire
transfer of immediately available funds to Worldwide’s account set forth below:

 

	 	Account Holder:	Worldwide Clinical Trials, Inc.
	 	Bank Name:	HSBC Bank USA, NA

 

    Page 4 of 47

     

    

 

	 	Bank Address: 	445 North Bedford Dr.
	 	 	Beverly Hills, CA 90210
	 	ABA Routing No.: 	021001088
	 	Bank Account No.: 	167-74758-4
	 	Swift Code:	MRMDUS33
	 	Taxpayer ID#: 	26-0902850

 

3.5       Project
Delays

 

In the event Sponsor delays, suspends or
places a hold on the Study for any reason, Sponsor shall promptly provide Worldwide with written notice of such delay, hold or
suspension, and Sponsor and Worldwide will, within 30 days of such notice, agree on appropriate revisions to this Agreement and
each Party will complete its respective duties and obligations as described in any resulting Change Order. During the period following
Worldwide’s receipt of Sponsor’s notice of delay, hold or suspension, if Sponsor desires Worldwide to continue the
assignment of certain Worldwide Study personnel to the Study, in addition to any other payments due to Worldwide hereunder, Sponsor
agrees that it shall pay for such special personnel fees associated with such continued assignment at a negotiated rate, such negotiated
rate to be agreed upon by the Parties prior to commencement of the delay, as evidenced by a Change Order. Said personnel fees shall
be invoiced by Worldwide on a monthly basis and shall be due and payable by Sponsor within forty-five (45) days of Sponsor’s
receipt of Worldwide’s invoice. If Sponsor does not wish to retain certain Worldwide Study personnel for the duration of
the delay or on hold period, Worldwide shall have the right to reallocate any and all such staff after such thirty (30) calendar
day period. If the delay or on-hold period continues for ninety (90) days either Party may, by provision of written notice, terminate
this Agreement without penalty.

 

3.6       Currency
Management

 

All invoices and amounts to be paid under
this Agreement shall be in US currency.

 

3.7       Disputed
Invoices

 

In the event Sponsor disputes one or more
items in an invoice, Sponsor will notify Worldwide in writing within thirty (30) business days of receipt of the invoice and such
notice shall contain a reasonably detailed description of the item(s) being disputed and the basis therefor. Worldwide will respond
to Sponsor within ten (10) business days of receipt of the notification. This written communication pattern will continue until
Worldwide has provided Sponsor with sufficient justification for the disputed item(s) or until the Parties agree to a resolution
of the disputed amount. Sponsor shall pay the undisputed portion of the invoice within forty-five (45) days of receipt of invoice
and shall use its reasonable efforts to pay the disputed amount within fifteen (15) days of resolution of the dispute pursuant
to Section 17.12. In the event the Parties are unable to reach a satisfactory resolution within sixty (60) days of the original
invoice, either Party may pursue alternative remedies in accordance with this Agreement.

 

4.0       THIRD
PARTY AGREEMENTS

 

Worldwide may contract with various
third parties to perform part of the Services, with the prior written consent of the Sponsor, provided that (i) the
subcontractor agrees in writing to be bound by terms consistent with this Agreement, including without limitation, regarding
maintaining the confidentiality of proprietary information, and regarding ownership of intellectual property in connection
with the Services, assignment to Sponsor of any intellectual property in connection with the Services; (ii) Worldwide shall
use its best efforts to ensure that any subcontractor has the capability to perform the subcontracted services to the
standards required under this Agreement and in compliance with Applicable Laws, (iii) Worldwide shall remain primarily
responsible to Sponsor for the performance of such subcontracted Services, and (iv) any subcontracting shall not relieve
Worldwide of its obligations hereunder and Worldwide hereby agrees to manage the performance of any permitted
subcontractor.

 

    Page 5 of 47

     

    

 

For purposes of this Agreement, subcontractors
do not include third party vendors providing ancillary services on the Study, provided that Worldwide’s agreement with any
such third-party vendor includes a provision making Sponsor an intended third-party beneficiary of the agreement with a right to
enforce Worldwide’s rights under the agreement. Liability of Worldwide to Sponsor with respect to such third-party vendors
shall be limited to the extent Worldwide is negligent in the performance of its obligations under this Agreement; however, Worldwide
shall provide to Sponsor any amounts that Worldwide may recover from such third party vendors as a result of any error or service
failure on the part of such vendors in connection with Services under this Agreement.

 

If Sponsor requests that Worldwide use
a particular third party and Worldwide does not wish to contract with that third party based upon commercially reasonable reasons
(such as the inability to agree with such provider upon mutually acceptable terms or a negative assessment of such provider’s
performance or abilities), then Sponsor shall contract directly with such provider (a “Sponsor Designated Vendor”)
and, unless otherwise agreed in writing, Worldwide will have no responsibility for the selection, instruction or supervision of
such Sponsor Designated Vendor.

 

4.1       Institutions/Investigators

 

Worldwide’s Services under this Agreement
may include identifying potential medical institutions (“Institutions”) or clinical investigators (“Investigators”)
and/or negotiating, executing and/or administering contracts with such parties which will govern their participation in the Study
(“Clinical Trial Agreements”). If, pursuant to the Scope of Services, Sponsor delegates to Worldwide the responsibility
for negotiating and/or executing Clinical Trial Agreements, the following provisions will apply:

 

		(a)	Sponsor may provide Worldwide with a list of suggested Institutions and/or Investigators to be
recruited by Worldwide for a Study. Worldwide shall notify Sponsor in writing as to any listed Institution/Investigator with which
Worldwide does not wish to contract.

 

		(b)	Selection of all Institutions or Investigators will be subject to approval by Sponsor prior to
initiation of any Study-related activities involving that Institution/Investigator or the start of any negotiations with such Institution/Investigator.

 

		(c)	Each Clinical Trial Agreement shall be consistent with this Agreement. The Clinical Trial Agreement
used with each Institution and Investigator will be in a form approved in advance by Sponsor. Any
material changes to the form Clinical Trial Agreement shall be replaced with fall-back language that has been pre-approved by Sponsor.
If outside of the fall-back language, the change shall require the prior written approval of the Sponsor.

 

	 	(d)	In the event that local law prohibits Sponsor from being a party to a Clinical Trial Agreement, Sponsor (a) shall have the right
to approve the Clinical Trial Agreement template; (b) shall be a named third-party beneficiary to each Clinical Trial Agreement
if possible; and, (c) shall have the right but no obligation to approve all finalized Clinical Trial Agreements prior to execution
by Worldwide.

 

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		(e)	If an Institution/Investigator requests indemnification from Sponsor, standard indemnification
language, generated by the Sponsor, will be provided to the Institution/Investigator. If the Institution/Investigator requests
changes to the standard language, Sponsor will negotiate
with the Institution/Investigator, if agreed, Sponsor will issue a letter of indemnification directly to the Institution/Investigator.
Sponsor acknowledges that Worldwide shall have no indemnification obligation to any Institution/Investigator relative to the Study
Drug or the applicable Study protocol. In addition, Worldwide shall not be deemed to have failed to perform under this Agreement
in the event an Institution/Investigator declines participation in a Study as a result of Sponsor’s refusal to indemnify
such Institution/Investigator.

  

		(f)	The Sponsor may elect that grant payments to Institutions/Investigators be administered on its
behalf by Worldwide, acting solely as payment agent unless otherwise agreed to by Worldwide in writing. Worldwide shall distribute
all payments to Institutions/Investigators according to the provisions of the applicable Clinical Trial Agreement and this Agreement.
Sponsor acknowledges and agrees that Worldwide will manage all administration of payments or other obligations to Investigators/Institutions
for Services rendered in connection with relevant Studies solely out of funds provided to Worldwide from Sponsor for this specific
purpose. Furthermore, Sponsor acknowledges and agrees that Worldwide intends to maintain a cash neutral policy with regard to Institutions/Investigators
payments. In the event Worldwide or the Institutions/Investigators incur bank fees with respect to the remittance of these grant
payments, such fees will be borne by Sponsor. All payments to Institutions/Investigators and any associated bank fees will be made
by Worldwide solely from the funds that have been specifically provided by Sponsor to Worldwide for this purpose and not from Worldwide
funds. Worldwide will not be liable for payments not made on a timely basis to any Institution/Investigator as a result of Sponsor’s
failure to provide, in advance, sufficient funds for such payments.

 

The Parties acknowledge and agree that,
for the purposes of this Agreement, Institutions/Investigators shall not be considered as employees, agents or subcontractors of
Worldwide and that Investigators will be required to exercise their own independent medical judgement. Worldwide’s responsibilities
with respect to Institutions/Investigators shall be limited to those specifically set forth in this Agreement.

 

5.0       CONFIDENTIAL
INFORMATION

 

The Parties acknowledge and agree that
in the course of performing Services hereunder, either Party may be exposed to or be given confidential or proprietary information
of the other Party (“Confidential Information”). The Parties agree to hold all Confidential Information in secrecy
for a period of ten (10) years from the effective date of the expiration or earlier termination of this Agreement and shall disclose
Confidential Information to third parties only on a need-to-know basis. Without limiting the generality of the foregoing, Confidential
Information shall include, without limitation, financial information, protocols, brochures, formulations, research and development
programs, methodology, testing techniques, analytical test method, test samples and prototypes, information gathered or viewed
during a site visit, audit or inspection of a Party, analyses, software, source codes and technological or other know-how. Confidential
Information shall be deemed to be all such information given by the disclosing party to the receiving party except for information
which is (i) publicly available or later becomes publicly available through no fault of the receiving party; (ii) obtained by the
receiving party from a third party entitled to disclose it; (iii) already in possession of the receiving party as indicated in
its written records; (iv) independently developed by the receiving party without use of the Confidential Information; or (v) required
by any law, rule, regulation, order, decision, decree, or subpoena or other judicial, administrative, or legal process to be disclosed.

 

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Both Parties shall ensure that all of its
officers, employees, consultants, agents, investigators or contractors who receive such Confidential Information understand and
shall be bound by the confidentiality provisions of this Agreement.

  

Unless otherwise agreed in writing, within
thirty (30) days after the termination of the Agreement or the written request by the disclosing party, the receiving party shall
return to the disclosing party all Confidential Information in documentary or permanent form including any and all copies thereof,
except for one archival copy that the receiving party can keep for its records (which may be electronic). The Parties agree that
each party is and shall remain the exclusive owner of its own Confidential Information and all patent, copyright, trade secret
and other intellectual property rights therein unless and until a further agreement is executed.

 

The Parties acknowledge that any violation
of the terms of this Section 5.0 may result in irreparable injury and damage to disclosing party that is not adequately compensable
in money damages, and for which disclosing party may have no adequate remedy at law. Accordingly, the receiving party agrees that
the disclosing party shall be entitled to seek (without waiving any additional rights or remedies, including monetary damages,
otherwise available to the disclosing party at law, in equity, or by statute) preliminary and permanent injunctive relief in the
event of a breach or intended or threatened breach by the receiving party.

 

6.0       OWNERSHIP
OF DATA AND INTELLECTUAL PROPERTY

 

Any invention, discovery, processes, know-how,
trade secrets, data, copyrights, trademarks, improvements, or any other intellectual property right related to Sponsor’s
products or technology, including the Study Drug, the Protocol, Sponsor’s Confidential Information, which is conceived or
reduced to practice as a result of the performance of the Services hereunder (the “Inventions”) shall become
Sponsor property and shall be used by Sponsor as Sponsor deems appropriate. Worldwide agrees to, and shall contractually require
and use reasonable efforts to cause Institutions and Investigators to execute and have executed assignments of the Inventions to
Sponsor, along with other documents that be necessary or helpful to Sponsor in filing patent applications, or which may relate
to any litigation or interference and/or controversy in connection therewith. The entire control, prosecution, and conduct of any
patent application filed by Sponsor shall be outside the jurisdiction of and without expense to Worldwide and its officers, employees,
representatives and agents. Worldwide acknowledges that Sponsor has the exclusive right to file patent applications in connection
with the Inventions. Worldwide warrants that neither it, nor its employees, agents and representatives, will prevent Sponsor from
filing patent applications for, or from applying the results of the research carried out for Sponsor hereunder.

 

All reports, data, technical information,
original works of authorship and all other information, furnished by or on behalf of Sponsor, or created specifically for Sponsor
as a deliverable under a this Agreement, shall be the sole property of Sponsor. Nothing under this Section or any other Section
of this Agreement shall be construed as (i) granting to any Party any rights under any patent, copyright or other intellectual
property right of the other Party (ii) granting to any Party any rights in or to the Confidential Information of the other Party
other than the limited right to use such Confidential Information solely for the purposes expressly permitted by Section 5.0 of
this Agreement.

 

    Page 8 of 47

     

    

 

Sponsor acknowledges that Worldwide
possesses certain computer programs, applications, algorithms, databases, methods, techniques, processes and other materials
and ideas independently developed by Worldwide which do not rely upon, reference, or inextricably incorporate Sponsor
Confidential Information or Study Drug and which relate to Worldwide’s business or operations (“Worldwide
Works”). All Worldwide Works, and all revisions, improvements and enhancements thereto, are the exclusive property
of Worldwide or its licensors. Sponsor agrees that any improvements, alterations or enhancements to the Worldwide Works
during the term of this Agreement or the Study shall be the sole property of Worldwide. Subject to Section 5.0 hereof, in no
event shall Worldwide be precluded from use of its general knowledge, skills and experience, and any of its ideas, concepts,
know-how and techniques used or developed by it in the course of providing Services under this Agreement. Worldwide
represents and warrants that it is entitled to deliver Worldwide Works where the same is delivered as part of the Services
hereunder for Sponsor and its Affiliates’ use, and Worldwide further represents and warrants that use by Sponsor and
its Affiliates’ of any such Worldwide Works is properly authorized and will not constitute an infringement or other
violation of any rights of any third party.

 

7.0       TERM
AND TERMINATION

 

7.1        Term

 

Unless earlier terminated according to
Sections 7.2-7.5 below, this Agreement will remain in effect from the date first written above until Worldwide has completed performance
of all Services (including delivery of all deliverables) and Worldwide has received from Sponsor all of the payments due hereunder.

 

7.2       Termination
for Material Breach 

 

In the event that either Party commits
a material breach in any of the terms or conditions of this Agreement, and that Party fails to cure the breach within thirty (30)
days after receipt of notice of the default or breach from the other Party, the Party giving notice may, at its option, immediately
terminate this Agreement at the end of the 30-day period. For the avoidance of doubt, non-payment of undisputed invoices by Sponsor
or non-payment by Worldwide to Institutions/Investigators under Section 4.1(f) shall automatically be deemed a material breach.

 

7.3       Termination
by Sponsor without Cause

 

Sponsor shall have the right to terminate
this Agreement (for other than breach by Worldwide) at any time by giving appropriate written notice at least sixty (60) days prior
to the desired termination date.

 

7.4       Termination
for Other Reasons

 

Sponsor shall have the right to terminate
this Agreement due to patient safety at any time by giving appropriate written notice. Either Party shall have the right to terminate
this Agreement at any time upon receipt of written notice to the other Party, if the other Party shall be adjudicated insolvent
or shall petition for or consent to any relief under any insolvency, re-organization, receivership, liquidation, compromise, or
any moratorium statute, whether now or hereafter in effect, or shall make an assignment for the benefit of its creditors, or shall
petition for the appointment of a receiver, liquidator, trustee, or custodian for all or a substantial part of its assets, or if
a receiver, liquidator, trustee or custodian is appointed for all or a substantial part of its assets and is not discharged within
thirty (30) days after the date of such appointment. In the event that any of the above events occur, that Party shall immediately
notify the other, in writing, of its occurrence.

 

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7.5       Termination
Procedures

 

Upon termination of this Agreement,
the Parties will reasonably cooperate with each other to provide for an orderly cessation of Worldwide’s Services.
Worldwide shall use its commercially reasonable efforts to minimize costs associated with the cessation of the Services. In
the event Sponsor terminates only part of the Services, the Parties will cooperate in good faith to enter into a Change Order
amending the terms of this Agreement accordingly. In the event the Agreement or any of the Services is terminated, Worldwide
will be entitled to receive payment for Services
performed (based on units completed) and pre-approved expenses actually incurred or irrevocably committed to third parties
(excluding salary and overhead) up to the effective date of termination. In addition, Sponsor shall pay all reasonable fees
and expenses incurred by Worldwide that are necessary or reasonably required in connection with the orderly cessation of the
Services. If a Study or the Agreement is cancelled or terminated before the Services have been performed completely,
Worldwide shall refund to Sponsor any funds advanced to Worldwide for fees and costs not yet incurred or due to the extent
that the payments for the liabilities associated with such fees or costs can reasonably be avoided in whole or in part. 

 

8.0       DEBARMENT
CERTIFICATION

 

Worldwide and its Affiliates represent
and certify that neither they, nor any of their respective employees or Study personnel have ever been (a) debarred or voluntarily
excluded or convicted of a crime for which a person can be debarred under Section 306 of the Federal Food, Drug, and Cosmetic Act,
21 U.S.C. §335a(a) , as amended, or any equivalent local law, regulation or guidelines thereof, in any country in which any
portion of the Study is conducted (“§335a”); nor (b) threatened to be debarred or voluntarily excluded or indicted
for a crime or otherwise engaged in conduct for which a person can be debarred under § 335a, or subject to any governmental
sanction that would prevent the rendering of Services hereunder in any jurisdiction in which the Study is to be conducted, nor
(c) excluded from participation in any federally-funded health-care program. Worldwide agrees that it shall notify Sponsor in writing
within 2 days in the event of any debarment, voluntary exclusion, conviction, threat, indictment or exclusion prohibited by this
Section occurring during the Term of this Agreement and will suspend all activity of such individual immediately upon notification
of investigation or debarment.

 

Worldwide represents and certifies that
it has not and will not knowingly use in any capacity the services of any individual, corporation, partnership, or association
which has been (a) debarred or voluntarily excluded or convicted of a crime for which a person can be debarred under § 335a;
(b) threatened to be debarred or voluntarily excluded or indicted for a crime or otherwise engaged in conduct for which a person
can be debarred under § 335a, or subject to any governmental sanction that would prevent the rendering of Services hereunder
in any jurisdiction in which the Study is to be conducted or (c) excluded from participation in any federally funded health care
program.

 

		9.0	RECORDS, AUDITS AND INSPECTIONS

  

		9.1	Records

 

Worldwide shall keep full and accurate
records and accounts of all its activities in connection with this Agreement, including reasonable substantiation of all Services
provided, expenses incurred. Additionally, Worldwide shall maintain a system of internal controls sufficient to provide reasonable
assurance that all transactions related to this Agreement are executed and are properly recorded in Worldwide’s books and
records. All records relating to this Agreement including, but not limited to, Worldwide’s invoices shall be available for
inspection and audit by Sponsor as set forth in Section 9.2, or any independent auditors designated by Sponsor, upon ten business
days prior written notice, and for a period of four (4) years following the completion of the Study, unless a longer retention
period is required by Applicable Laws. Sponsor agrees that its independent auditors may be required to execute a reasonable confidentiality
agreement with Worldwide or Worldwide’s Affiliate or subsidiary, as the case may be, which contains mutually agreed-upon
terms. Further, Sponsor’s financial audit of Worldwide or any Worldwide Affiliate or subsidiary hereunder shall be subject
to the confidentiality obligations set forth herein.

 

    Page 10 of 47

     

    

 

		9.2	Audits by Sponsor

 

During
the term of this Agreement, Worldwide will permit representatives of Sponsor who are not competitors of Worldwide to examine, at
reasonable times during normal business hours, subject to at least ten (10) business days prior written notice to Worldwide (except
in the case of “for cause” audits where Sponsor will provide three (3) business days prior written notice to Worldwide),
and at Sponsor’s sole cost and expense: (i) the facilities where the Services are being, will be or have been conducted;
(ii) related Study documentation; and (iii) any other relevant information necessary for Sponsor to confirm that the Services are
being or will be or have been conducted in conformance with applicable standard operating procedures, this Agreement and in compliance
with Applicable Laws and regulations, including related financial information relating to Worldwide service fees, Pass-through
Expenses and grant payments to Investigators. Worldwide will provide copies of any materials reasonably requested by Sponsor during
such inspection.

  

		9.3	Inspection by Regulatory Authorities

 

During the term of this Agreement, Worldwide
will permit regulatory authorities to examine, (i) the facilities where the Services are being conducted; (ii) study documentation;
and (iii) any other relevant information, including information that may be designated by Worldwide as confidential, reasonably
necessary for regulatory authorities to confirm that the Services are being conducted in compliance with Applicable Laws and regulations.
Worldwide will immediately notify Sponsor if any regulatory authority schedules, or without scheduling, begins an inspection that
relates to the Services, and, unless expressly prohibited by such regulatory authority, permit Sponsor to attend such inspection.

 

9.4       Inspections
of Investigator Site(s) by Worldwide

 

In connection with Worldwide’s provision
of Services as specified in this Agreement, Worldwide may conduct monitoring visits and/or inspections of Investigator Sites. Based
on Worldwide’s observations during such Investigator Site visits and inspections, Worldwide may decide: i) that enrollment
should be suspended at the Investigator Site; ii) that an Investigator Site’s non-compliance needs to be reported to Sponsor
and/or regulatory authorities; and/or (iii) Investigator Site’s participation in a Study needs to be terminated. Upon such
a determination, Worldwide will present to Sponsor a basis for its decision. If Sponsor disagrees with the basis for Worldwide’s
decision, Worldwide will assign its contract with the Investigator Site to Sponsor and Sponsor agrees to accept such assignment
and to be responsible for all contractual duties and obligations to the Investigator Site.

  

10.0       INDEMNIFICATION

 

10.1       Indemnification
by Worldwide

 

Worldwide shall indemnify, defend and hold
harmless Sponsor and its Affiliates and their respective officers, directors, employees and agents from any loss, damage, cost
or expense (including reasonable attorney’s fees) (“Losses”) arising from any third party claim, demand,
assessment, action, suit or proceeding (a “Claim”) arising out of (i) any material breach by Worldwide Group
of any material obligations under this Agreement or the Protocol, (ii) any Worldwide Group’s negligence or intentional misconduct;
or (iii) any Worldwide Group’s material failure to comply with any applicable law for FDA regulations, except to the extent
such Losses are caused by Sponsor’s negligence or willful misconduct.

  

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10.2       Indemnification
by Sponsor

 

Sponsor shall indemnify,
defend and hold harmless Worldwide and its Affiliates and their respective officers, directors, employees and agents (the “Worldwide
Group”) from any Losses arising from any Claim arising out of (i) Worldwide’s adherence to written instructions
provided by Sponsor to Worldwide, including adherence to the Protocol and proper performance of the Services in accordance with
this Agreement and the Protocol; (ii) the Study drug’s harmful or otherwise adverse effect, including, without limitation,
a Claim based upon the consumption, sale, distribution or marketing of any substance, including the Study drug, (iii)any breach
by Sponsor of any material obligations under this Agreement, or (iv) the negligence or intentional misconduct of Sponsor, except
to the extent such Losses are caused by Worldwide Group’s negligence or wilful misconduct.

 

In the event Worldwide
incurs reasonable and necessary costs or out-of-pocket expenses as a result of it becoming involved in, or being required to appear
or otherwise participate in, a matter (i) relating to the Study that is the subject of a claim or any proceeding, litigation, arbitration
or some other dispute resolution mechanism, and (ii) where Worldwide’s performance of the Services in a manner other than
in compliance with this Agreement is not at issue in such claim, then Sponsor shall reimburse Worldwide for pre-approved reasonable
and necessary costs or out-of-pocket expenses. The Parties agree to cooperate with each other and to use commercially reasonable
best efforts in good faith to minimize Worldwide’s participation in and the costs or out-of-pocket expenses relating to such
disputes.

 

10.3       Indemnification
Procedures

 

Upon receipt of written
notice of any Claim which may give rise to a right of indemnity from the other Party hereto, the Party seeking indemnification
(the “Indemnified Party”) shall give written notice thereof to the other Party, (the “Indemnifying
Party”). The Indemnified Party shall permit the Indemnifying Party, at its own option and expense, to assume the complete
defense of such Claim, provided that the Indemnified Party will have the right to participate in the defense of any such Claim
at its own cost and expense. As to those Claims with respect to which the Indemnifying Party does not elect to assume control,
the Indemnified Party will afford the Indemnifying Party an opportunity to participate in such defense, at the Indemnifying Party’s
own cost and expense.

 

 

11.0       LIMITATION
OF LIABILITY

 

Under no circumstances shall either Party
be liable under this Agreement for any indirect, incidental, special or consequential damages of the other Party resulting from
such Party’s performance or failure to perform under this Agreement. In addition and except for the confidentiality and indemnification
obligations of Worldwide under Sections 5 and 10.1, respectively, in no event shall the collective, aggregate liability of the
Worldwide Group to Sponsor exceed one and one-half times the amount of fees due or actually paid by Sponsor to Worldwide pursuant
to this Agreement.

 

12.0       INSURANCE

 

Sponsor hereby
represents and warrants that it shall maintain adequate clinical trial and product liability insurance coverage, with
insurance companies having an A. M. Best Rating of "A-, VII" or better, consistent with industry standards to cover
all personal injury, death or loss suffered as a result of the Study Drug, participation in the trial or the trial screening
process. Sponsor shall provide Worldwide with a copy of Sponsor’s effective Certificate of Insurance or such other
documented evidence to confirm that it has such coverage. Sponsor shall maintain such insurance for the entire duration of
the Study and shall notify Worldwide of any changes in coverage which impact the coverage requirements set forth above.

 

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Prior to commencement of any work under
this Agreement, Worldwide shall, at its sole expense, maintain the following insurance on its own behalf, with insurance companies
having an A. M. Best Rating of "A-, VII", or better:

 

		(1)	Commercial General Liability (including Premises Operations).
The policy must be on an occurrence form and include the following limits: Each Occurrence: $1,000,000; General Aggregate: $2,000,000.

 

		(2)	Commercial Umbrella Liability. This policy must include
the following limits: Occurrence Limit: $4,000,000; Aggregate Limit (where applicable); $4,000,000 Policy to be excess of the
Commercial General Liability, Commercial Automobile Liability and Employers Liability.

 

		(3)	Product/Professional Liability Coverage (Errors &
Omissions): Each Claim Limit: $ 10,000,000; Aggregate Limit: $10,000,000. Throughout the term of this Agreement, the Errors &
Omissions Liability insurance's retroactive date will be no later than the effective date of this agreement. Upon expiration or
termination of this Agreement, Worldwide will either continue to maintain an active insurance policy, or purchase an extended
reporting period coverage for claims first made and reported to the insurance company within sixty (60) months after the end of
the Agreement.

 

Upon request, Worldwide shall provide Sponsor
with a copy of Worldwide’s Certificates of Insurance or such other documented evidence to confirm that it has all of the
foregoing coverage. Worldwide shall maintain such insurance for the entire duration of the Study and shall notify Sponsor of any
reduction in coverage which impact the coverage requirements set forth above.

 

13.0       REPRESENTATIONS
AND WARRANTIES

 

13.1       Each
Party represents that it is authorized to enter into this Agreement and that the terms of this Agreement are not inconsistent with
or a violation of any contracted or other legal obligation to which it is subject.

 

13.2       Each
Party represents that it has all qualifications, authorizations, licenses or permits which are necessary for performance of its
obligations under this Agreement.

 

13.3       Worldwide
represents and warrants to Sponsor that:

 

(a)       Worldwide
is a duly incorporated and validly existing corporation under the laws of the Delaware;

 

(b)       Worldwide
represents that taken together with its Affiliates it has personnel, equipment, experience and expertise sufficient in quality
and quantity to provide all comprehensive Services requested by Sponsor hereunder and agreed to by Worldwide and its Affiliates
and that any and all such Services will be performed commensurate with the commercially reasonable standards generally applicable
to the conduct and management of clinical drug studies by a clinical research organization throughout the world;

 

(c)       upon
execution and delivery of this Agreement, this Agreement shall constitute a legal, valid and binding agreement of Worldwide
and its Affiliates, as applicable, enforceable in accordance with its terms, except to the extent enforceability may be
affected by applicable bankruptcy, reorganization, insolvency, and moratorium laws and other laws applicable generally to
creditors’ rights and debtors’ remedies from time to time in effect;

 

    Page 13 of 47

     

    

 

(d)       neither
the execution and delivery of this Agreement nor Worldwide’s performance of its obligations hereunder will violate or breach,
or otherwise constitute or give rise to a default under, the terms or provisions of Worldwide’s registration documents or
its By-Laws or any equivalent document or of any material contract, commitment or other obligation to which Worldwide is a party,
or violate or result in a breach of or constitute a default under any judgment, order, decree, rule or regulation of any court
or governmental agency to which Worldwide is subject; and

 

(e)       Worldwide
has developed a business interruption and disaster recovery program and is executing such program to assess and reduce the extent
to which Worldwide’s hardware, software and embedded systems may be susceptible to errors or failures in various crisis (or
force majeure) situations. In the event that any data, reports or materials that are delivered by Worldwide to Sponsor are inaccurate,
and Worldwide does not reasonably dispute such inaccuracy, and such inaccuracy is caused by errors or failures of Worldwide’s
personnel, hardware, software or embedded systems then Worldwide will, to the extent possible, fix, or if necessary, re-perform
the deliverables at its own expense within mutually agreeable time frames. If Sponsor and Worldwide mutually agree that Worldwide
is not capable of timely or satisfactory re-performance and Worldwide has been paid for such Services, then Worldwide will reimburse
Sponsor for the reasonable costs related to a third party’s re-performance of such services or reimburse Sponsor for the
reasonable internal costs allocated for the re-performance of such services; provided, however, such reimbursement shall not exceed
the amount of money Worldwide received for the performance the inaccurate Services.

 

(f)     Worldwide will
employ commercially reasonable efforts to ensure that all data collected and stored by it pursuant to this Agreement will be safeguarded
against loss, damage and destruction arising from any cause including, but not limited to, theft, fire, flood, earthquake, lightning,
and electrical disruption. Such measures and processes will include, but not be limited to, (a) storage of hard-copy documents
and computer storage disks in locked, fireproof containers, and (b) back-up and recovery systems (which are periodically tested)
for computer-based systems. Sponsor has the right, but not the obligation, subject to at least ten (10) business days prior written
notice to Worldwide, during normal business hours and at mutually agreed upon dates and times, to periodically inspect Worldwide’s
premises to determine whether the foregoing measures and processes are in effect and being implemented. Such inspections shall
be subject to the confidentiality obligations set forth herein.

 

14.0        DISCLAIMER

 

Sponsor acknowledges that the results of
the Studies for which the Services are to be provided hereunder are inherently uncertain and that, accordingly, there can be no
assurance, representation or warranty by Worldwide that the product covered by this Agreement can, either during the term of this
Agreement or thereafter, be successfully developed or receive the required approval by the regulatory authorities.

 

Sponsor acknowledges that the development
of the protocol concept and scientific rationale shall be the sole responsibility of Sponsor regardless of Worldwide’s involvement
in Study design or protocol-writing (or lack thereof).

 

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15.0       EMPLOYEES;
NON-SOLICITATION

 

Worldwide’s staff is not, nor shall
they be deemed to be at any time during the term of this Agreement, the employees of Sponsor. In consideration of the fees and
benefits provided in this Agreement, Sponsor agrees that, without Worldwide’s prior written consent, during the term of this
Agreement and for a period of twelve (12) months following its expiration or other termination, neither Sponsor nor any of its
Affiliates shall directly or indirectly solicit for employment or contract, attempt to employ or contract with, or assist any other
entity in employing, contracting with or soliciting for employment or contract any employee who is at that time employed/contracted
by Worldwide and who had been employed/contracted by Worldwide in connection with this Agreement issued hereunder. In the event
that legal action becomes necessary for the enforcement of all or any part of this provision, the prevailing party shall receive
in addition to any other damages or relief awarded, its reasonable attorneys’ fees, together with appropriate costs and interest.
Sponsor acknowledges that in the event of a breach of this Section 15.0, Worldwide shall be entitled to seek injunctive relief
for any such breach.

 

16.0       NOTICES

 

All notices provided for in this Agreement
shall be in English and shall be sent by registered first class mail, postage prepaid, return receipt requested, addressed to the
respective Parties as follows:

 

If to Sponsor:

 

Neurotrope Bioscience, Inc.

205 East 42nd Street,
New York, NY 10019

ATTN: Robert Weinstein

Chief Financial
Officer

Via email:
rweinstein@neurotropebioscience.com

 

If to Worldwide:

 

c/o Worldwide
Clinical Trials, Inc.

3800 Paramount
Parkway, Suite 400, 27560

Morrisville,
NC, United States

ATTN: Legal
Counsel

 

17.0       MISCELLANEOUS

 

17.1        Modification

 

This Agreement may be supplemented, amended
or modified only by mutual agreement of the Parties. No supplement, modification or amendment of this Agreement will be binding
unless it is in writing and signed by both Parties.

 

17.2       Assignment

 

Neither Party shall have the right to
assign this Agreement or any of its rights or obligations hereunder without the prior written consent of the other Party,
except that either Party may assign this Agreement to an Affiliate, any purchaser of or successor to that area of its
business to which this Agreement is related, any purchaser of all or substantially all of such Party’s assets or in
excess of 50% of such Party’s voting securities, and any successor corporation resulting from any merger,
consolidation, reorganization, business organization, joint venture or similar transaction of such Party with or into such
corporation. Worldwide assignment, delegation or subcontracting to any third parties shall be in accordance with the terms of
this Agreement. Any permitted assignment by either party will not relieve such Party of its obligations or liability incurred
prior to assignment. Any assignment not in compliance with the terms of this provision shall be void.

 

    Page 15 of 47

     

    

 

17.3       Force
Majeure

 

Neither Sponsor nor Worldwide shall be
liable for delays in performing or any failure to perform any of the terms of this Agreement caused by the effects of fire, strike,
war (declared or undeclared), insurrection, acts of terror, government restriction or prohibition, or other causes reasonably beyond
its control and without its fault, but the Party failing to perform shall use all commercially reasonable efforts to resume performance
of this Agreement as soon as feasible. Any episode of force majeure which continues for 30 days from the date of notification of
its existence shall give the non-affected Party the right to terminate this Agreement upon 30 days additional notice.

 

17.4       Severability

 

If any provision of this Agreement is found
by a court to be void, invalid or unenforceable, the same shall either be reformed to comply with applicable laws and regulations
or stricken if not so conformable, so as not to affect the validity or enforceability of the remaining provisions of this Agreement,
except if the principal intent of this Agreement is frustrated by such reformation or deletion in which case this Agreement shall
terminate.

 

17.5       English
Language

 

Unless the Parties otherwise agree, any
document that is provided in connection with this Agreement must be (a) in English, or (b) accompanied by a certified English translation,
in which case the English translation shall prevail unless the document is a statutory or other official document.

 

17.6       Entire
Agreement

 

The Parties hereto acknowledge that each
has read this Agreement, understands it and agrees to be bound by its terms. The Parties agree that this Agreement is the complete
agreement between the Parties on the subject matter and supersedes all proposals (oral or written), letters of intent, understandings,
representations, conditions, warranties, covenants and other communications between the Parties relating to the same subject matter.

 

17.7       Survival

 

The terms, contained in Section 3, Sections
6.0, 7.6, 8.0, 10.0, 11.0, and 17.0 of this Agreement shall survive the completion of performance, expiration or termination of
this Agreement. Sections 5.0, and 15.0 shall survive for the period expressly set forth in such Section or, if none, the applicable
statute of limitations period applicable to a claim for breach of such provision.

 

17.8       Governing
Law

 

This Agreement shall be interpreted and
enforced in accordance with the laws of the State of Delaware and each Party hereby specifically consents to the personal jurisdiction
thereof.

 

17.9       Waiver

 

No waiver of any term, provision or condition
of this Agreement whether by conduct or otherwise in any one or more instances will be deemed to be construed as a further or continuing
waiver of such term, provision or condition or of any other term, provision or condition of this Agreement.

  

    Page 16 of 47

     

    

 

17.10       Independent
Contractors

 

The Parties’ relationship, as established
by this Agreement, is solely that of independent contractors. This Agreement does not create any partnership, joint venture or
similar business relationship between the Parties. Subject to Section 10.0 and/or as may be expressly agreed otherwise in the case
of legal representation in the EU, neither Party is a legal representative of the other Party, and neither Party can assume or
create any obligation, representation, warranty or guarantee, express or implied, on behalf of the other Party for any purpose
whatsoever.

 

17.11       Counterparts

 

This Agreement may be executed in counterparts,
each of which shall be deemed an original but all of which taken together shall constitute one and the same instrument. In the
event that any signature is delivered by facsimile transmission, by e-mail delivery of a “.pdf” format data file or
other electronic means, such signature shall create a valid and binding obligation of the party executing (or on whose behalf such
signature is executed) with the same force and effect as if such signature page were an original thereof.

 

17.12       Arbitration

 

In the event a dispute relating to this
Agreement arises between the Parties, the Parties shall confer in good faith to resolve the dispute through negotiations between
respective senior executives of the Parties. In the event that the Parties are unable to resolve the dispute, the Parties will
attempt to resolve the dispute in good faith through mediation. If the dispute has not been resolved by mediation within sixty
(60) days of the initiation of the procedure, the dispute shall be settled by arbitration administered by the American Arbitration
Association under its Commercial Arbitration Rules in Delaware. Judgment shall be rendered by a mutually agreed upon single arbitrator.
The provisions of this Section may be enforced by any court of competent jurisdiction, and the Party seeking enforcement shall
be entitled to an award of all costs, fees and expenses, including reasonable attorneys’ fees, to be paid by the Party against
whom enforcement is ordered.

 

 

IN WITNESS WHEREOF, the undersigned have
caused this Agreement to be executed by their respective duly authorized representatives effective as of the Effective Date.

 

	NEUROTROPE BIOSCIENCES, INC.	 	WORLDWIDE CLINICAL TRIALS, INC.
	 	 	 
	By:	/s/Robert Weinstein	 	By:	 /s/ Anthony Hinman

 

	Name:	 Robert Weinstein	 	Name:	 Anthony Hinman
	 	 	 
	Title:	 CFO	 	Title:	Legal Counsel
	 	 	 
	Date:	July 23, 2020	 	Date:	July 23, 2020

 

    Page 17 of 47

     

    

 

LIST OF EXHIBITS:

 

	EXHIBIT A:	 	Scope of Services	 
	EXHIBIT B:	 	Timeline	 
	EXHIBIT C:	 	Budget	 
	EXHIBIT D:	 	Payment Schedule	 
	EXHIBIT E:	 	Form of Change Order	 

 

    Page 18 of 47

     

    

 

EXHIBIT A

SCOPE OF SERVICES

 

Assumptions:

 

 

	Study Assumptions and Specifications
	General Study Information	 
	Drug/Compound	Bryostatin
	Indication	Alzheimer's Disease
	Study Phase	 Phase II
	Bid Currency	USD
	 	 
	Study Sites	 
	Number of Countries	1
	Number of Sites	20
	North America	20
	USA	20
	Patients	 
	Number of Screened Patients	220
	Number of Enrolled Patients	100
	Number of Drop Outs	15
	Number of Completed Patients	85
	Site Monitoring and Site Management	 
	Number of CRAs (Headcount Based)	3
	Monitoring Visits	 
	Number of Phone Qualification Visits	10
	Number of Site Qualification Visits	10
	Number of Site Initiation Visits	20
	Number of Remote Monitoring Visits	140
	Number of Interim Monitoring Visits	140
	Pool of Additional Visits	80
	Number of Close-outs Visits	20
	Site Maintenance Months	530
	Remote Data Review	390
	Meetings	 
	Internal Alignment (KO) Meeting	Yes
	Sponsor Alignment (KO) Meeting	Yes
	Project team teleconferences	Yes
	Number of internal teleconferences	82
	Number of sponsor teleconferences	82
	Site Activation	 
	Feasibility/ Site Identification	15
	Essential Documents & Review	20
	Investigator Agreements 	20
	Central Institutional Review Board (IRB) Site Submissions	20
	Medical Affairs	 
	Number of Months for Medical Planning	1

 

 

    Page 19 of 47

     

    

 

	Study Assumptions and Specifications

	Eligibility Review	220 Screened Subjects
	Listings Reviews	100 Enrolled Subjects
	Coded Data Review	100 Enrolled Subjects
	Ongoing Safety Reviews of Labs and ECG alerts	318 Alerts
	Pharmacovigilance	 
	Estimated Number of SAE(s)	11
	Estimated Number of Expedited SUSAR(s)	1
	Safety Database Setup and Maintenance	Argus Database
	Number of Follow-up Reports per Event	2
	Data Management	 
	CRF Pages	 
	Number of Pages/Enrolled Patient	225 Total per Patient

 (30 Unique)
	Number of Pages/Screen Fail Patient	23
	Clinical Data Management System	IBMCD
	Randomization System	IBMCD
	Number of Edit Checks	240
	Number of Dictionary Coding Terms (AEs, MedHistory, Medications)	2,500
	MedDRA Coding	1,000
	WHODRUG Coding 	1,500
	Number of External Vendor Data Loads	26
	Data Cleaning	23565 Pages
	Manual Listings	780
	Reconciliation of SAE(s)	11
	Number and Type of Database Transfers	9 Total Transfers
	Biometrics	 
	Statistical Analysis Plan	Yes
	Randomization Schedule	Yes
	Number and Type of Analyses:	 
	Dry Runs	Yes
	Full Analysis	1
	PK Analysis	Not Included
	Final Analysis Data Displays:	 
	Number of Tables	25 Unique / 50 Repeat
	Number of Listings	25 Unique
	Number of Figures/Graphs	10 Unique / 10 Repeat
	Datasets:	 
	Data sets SDTM	25 Datasets
	Data sets ADaM	15 Datasets
	Ongoing CDISC Transfers	5
	Medical Writing	 
	Informed Consent Form	3
	Clinical Study Report (Shell and body text)	Not Included
	CSR Published	Not Included
	Data Safety Monitoring Board (DSMB)	 
	Number of Meetings	2
	DSMB Data Displays	 

 

    Page 20 of 47

     

    

 

	Study Assumptions and Specifications

	Number of Tables	5 Unique / 18 Repeat
	Number of Listings	11 Unique
	Number of Figures/Graphs	5 Unique / 5 Repeat

 

Responsibilities:

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Feasibility/ Site Identification	X
	Identify Sites	X
	Unblinded Feasibility under Confidentiality Disclosure Agreement	X
	Site Activation Lead Planning Per Country	X
	Liaise with Global Project Lead, Regional Project Manager, Lead Clinical Research Associate and Site Activation Lead to Develop a Site Activation Strategy	X
	Communicate Start-up Timelines	X
	Develop a Risk Log and Priority Action Items	X
	Provide Strategic Input to Site Selection	X
	Develop Site Activation Tracker Template	X
	Trial Master File (TMF) Filing & QC	X
	Regulatory Project Plan	X
	Regulatory Set-up	X
	Set Up Electronic and Hardcopy Files	X
	Familiarize with Protocol, Investigator Brochure and Investigational Medicinal Product Dossier (IMPD)	X
	Set Up Trackers or Databases, Including Country Requirements	X
	Core Documents Master Templates	X
	Develop Master Templates for Core Documents 	X
	Essential Documents & Review (US)	X
	Prepare and Distribute Essential Documents Templates	X
	Customize Essential Document Templates with Site Specific Information	X
	Collect Essential Document from Sites	X
	Provide First Review of Essential Documents for Compliance	X
	Provide Second Review of Essential Documents for Compliance 	X
	Communicate Deficiencies to First Reviewer	X
	Sign Off Essential Documents Package	X
	Answer Questions or Provide Clarification and Training to Project Team on Process or Requirements	X
	Provide Weekly Tracking and Progress Reports	X
	File Essential Documents and Checklist (Electronic Trial Master File/ Trial Master File, Internal Filing)	X
	Essential Documents Review Plan	X
	Essential Documents Checklist	X

 

    Page 21 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility

	Investigator Agreements 	X
	Prepare Template	X
	Negotiate Site Contracts to Execution	X
	Ensure the Completion of Site Indemnification Letters	X
	Administrative Quality Control all Investigator Agreements	X
	Track Status of Investigator Agreements	X
	Coordinate all Required Translations	X
	Investigator Agreements Country Specific Templates	X
	Customize Master Template with Country, Project and Sponsor-specific Requirements 	X
	Arrange Translation into Local Languages	X
	Perform Final Review and Formatting	X
	Contract and Budget Plan (CBP)	X
	Prepare Contract and Budget Plan for Initial Strategy.  Any Substantial Amendments to the Contract and Budget Plan will Require a Contract Amendment	X
	Investigator Grant Build	X
	Build Grant Plan for the Study.  Any Substantial Amendments to the Country and Site Strategy will Require a New Build and Contract Amendment	X
	Submission Strategy & Risk Assessment	X
	Develop Submission Strategy and Perform a Risk Assessment	X
	Central Institutional Review Board (IRB) Site Submissions (US)	X
	Prepare Regulatory Packages for Initial Submission	X
	Complete Application Forms	X
	Quality Control all Packages Prior to Submission	X
	Submit Regulatory Packages to Central Institutional Review Board (IRB)	X
	Track Regulatory Package/ Submission Status	X
	Review & Customize Informed Consent Form	X
	Maintain Informed Consent Form Tracking Log	X
	Central Institutional Review Board (IRB) Submission, Study Level (US)	X
	Preparation of Package, Quality Control, Submission, Response to Queries at Study Level to the Central Institutional Review Board (IRB)	X
	Master Informed Consent Form (ICF) Review	X
	TMF Management Plan & TMF Risk Assessment	X

 

    Page 22 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility

	Draft, Review and Update Trial Master File Management Plan which Includes but is not Limited to:

- Project Timelines and Deliverables, i.e., Target Date of Submission of Trial Master File Documents to the Electronic Trial Master File Inbox by Submitters

- Define Electronic Trial Master File Configuration Requirements

- Delivery Intervals of Wet-ink Documents to Sponsor, if Required, (Quarterly, End of Study, etc.)

- Final Shipment of Trial Master File to Sponsor

- Forwarding applicable Records Management Compliance Standard Operating Procedures to sponsor, if needed.

- Listing of each wet-ink document required to be maintained during the course of the study

- Description of Quality Control/file reviews conducted by the project team

- Description of the Trial Master File close-out process	X
	Approve Trial Master File Management Plan	X
	Worldwide TMF: TMF Set-up: Pre Site Activation Activities	X
	Determine Trial Master File Filing Structure	X
	Review Trial Master File Management Plan for Sponsor-hosted Trial Master Files.  Check for Alignment with Worldwide's Record Management Compliance Standard Operating Procedures	X
	Provide Sponsor with Worldwide's Standard Operating Procedures Describing Trial Master File Document Protection (Scanning for Disaster Recovery), Secure File Area Conditions (Protection Against Fire/ Environmental Factors), and Secure Access to File Area Locations (Controlled and Restricted Access)	X
	Provide Detailed Expectations Regarding Type of Access Requirements of Sponsor and Worldwide's Project Team Including Timeframes for Access and Review	X
	Prepare Annotated Trial Master File Structure	X
	Prepare/ Configure the Trial Master File According to Worldwide's Standard Operating Procedures and Trial Master File Management Plan or Sponsor Plans if Sponsor-hosted Electronic Trial Master File.	X
	Agree Trial Master File Compliance Reporting Needs with the Sponsor	X
	Design Periodic Trial Master File Quality Control Process	X
	Facilitate Electronic Trial Master File System Training of all Users; Provide Project-specific Training Tools to Project Management	X
	Worldwide TMF: TMF Final Reconciliation & Transfer	X
	Complete Final Quality Control and Reconciliation of the Trial Master File	X
	Generate Trial Master File Gap Analysis for Review with Sponsor	X
	Complete a Final Review of the Trial Master File Data Due for Transfer	X
	Transfer Trial Master File Data to Sponsor 	X
	Obtain Signed Transfer of Ownership Form from Sponsor	X

 

    Page 23 of 47

     

    

 

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility

	Internal Alignment (KO) Meeting	X
	Prepare for Internal Alignment Meeting 	X
	Attend and Participate in Meeting	X
	Sponsor Alignment (KO) Meeting	X
	Prepare for Sponsor Alignment Meeting 	X
	Attend and Participate in Meeting	X
	Sponsor Teleconferences	X
	Prepare for Teleconference - Gather Metrics, Issues and Any Action Item Updates	X
	Attend and Participate in Meeting	X
	Internal Teleconferences	X
	Prepare for Teleconference - Gather Metrics, Issues and Any Action Item Updates	X
	Attend and Participate in Meeting	X
	Lead Clinical Research Associate Support	X
	Communicate with Sponsor, Project Team and Vendors	X
	Attend and Participate in the Internal Project Clinical Research Associate (CRA) Training	X
	Provide Project Oversight	X
	Create and Disseminate Project Metrics	X
	Create Study Monitoring Manuals, Plans and Tools 	X
	Review Vendor Portals (Not in Preparation for Site Visit or Meetings)	X
	Provide Ongoing Review of and Updates to Study tools, Trackers, Reports and Metrics	X
	Provide Ongoing Trial Master File Review 	X
	Organizes, Tracks and Ensures the Clinical Study Report is Delivered to All Sites, Institutional Review Boards, and Competent Authorities (In Countries Where Applicable).  Ensures Acknowledgment of Receipts are Available/ Filed.	X
	Site Management	X
	Communicate with Sites During Start-up, Conduct and Closure and Resolve Site Issues Throughout the Study	X
	Support Sites During Start-up, Sites Set-up (Includes Back-up Sites), Conduct and Closure	X
	Update Clinical Trial Management System as Needed	X
	Write Telephone Contact Reports	X
	Communicate with the Project Team Regarding Site Issues	X
	General Site Contact and Communication	X
	Provide Remote Monitoring 	X
	Follow Up with Sites on Protocol Violations/ Deviations and Queries/ Data Management Issues	X
	Provide Assistance with Investigational Medicinal Product (IMP) Site Issues (i.e. Shipment, Acknowledgement, Interactive Response Technologies Site Entry and Review review)	X
	Send/ Deliver Safety Information to Sites (if not performed by the Pharmacovigilance Team)	X

 

    Page 24 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility

	Communicate with Sites Regarding any Serious Adverse Events (SAE) Issues	X
	Provide Electronic Trial Master File Updates on an Ongoing Basis and Quality Control of Site Documents Collected in-between Site Visits	X
	Internal Clinical Research Associate Calls & Project Communication	X
	Clinical Research Associate Training (not at Investigator Meeting)	X
	Remote Pre-site Selection Visits	X
	Prepare for Visit	X
	Perform Visit (Remote)	X
	Write Visit Report	X
	Complete Visit Follow-up	X
	Review and Approve Visit Report	X
	On-site Pre-site Selection Visits	X
	Prepare for Visit	X
	Travel to and from Location	X
	Perform Visit	X
	Write Visit Report	X
	Complete Visit Follow-up	X
	Review and Approve Visit Report	X
	On-site Site Initiation Visits	X
	Prepare for Visit	X
	Travel to and from Location	X
	Perform Visit	X
	Write Visit Report	X
	Complete Visit follow-up	X
	Review and Approve Visit Report	X
	Remote Monitoring Visits Conduct 	X
	Prepare for Visit	X
	Perform Visit (Remote)	X
	Write Visit Report	X
	Complete Visit Follow-up	X
	Review and Approve Visit Report	X
	On-Site Monitoring Visits Conduct	X
	Prepare for Visit	X
	Travel to and from Location	X
	Perform Visit	X
	Write Visit Report	X
	Complete Visit Follow-up	X
	Review and Approve Visit Report	X
	Additional Time On-site	X
	On-site Close-out Visits	X
	Prepare for Visit	X
	Travel to and from Location	X
	Perform Visit	X
	Write Visit Report	X

 

    Page 25 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Complete Visit Follow-up	X
	Review and Approve Visit Report	X
	Reconcile Final Trial Master File	X
	Remote Electronic Data Capture (EDC) Review Conduct	X
	Set-up Grant Payments	X
	Enter New Payees into the Finance System	X
	Acquire and Save all W-9's (US Sites Only)	X
	Process Grant Payments 	X
	Initiate and Print Purchase Orders	X
	Process Check or Wire	X
	Enter Voucher and Payment Transactions into the Finance System	X
	Provide Status Updates	X
	Track and Record all Payments	X
	Process Site Cost Payments 	X
	Set-up Vendor Payments	X
	Enter New Payees into the Finance System 	X
	Acquire and Save all W-9's (US Sites Only)	X
	Process Vendor Payments	X
	Process Check or Wire upon Project Management Approval	X
	Enter Voucher and Payment Transactions into the Finance System	X
	Risk Based Quality Management	X
	Protocol Risk Assessment	X
	Database Set-up & Configuration	X
	Define Argus Database Specifications	X
	Build Database	X
	Test Database	X
	Validate Database	X
	Safety Management Plan Development	X
	Write Safety Management Plan to Define Roles and Responsibilities of the Sponsor and Worldwide and Describe the Procedures for the Management, Processing, and Reporting of Serious Adverse Events (SAE) and Pregnancies	X
	Arrange for Review and Incorporation of Comments	X
	Obtain Approval from All Relevant Parties	X
	Safety Training (Sites, Clinical Research Associates, Project Team)	X
	Develop Training Materials	X
	Train All Relevant Worldwide/ Sponsor/ Site Staff of Pharmacovigilance Requirements and Obligations	X
	Provide Follow-up Training as Required	X
	Serious Adverse Events (SAE) Processing, Investigation, Narrative, Approval & Query Generation 	X
	Assess Each Serious Adverse Event (SAE) for Seriousness, Listedness and Causality	X
	Review Coding, Querying and Narratives and Analyze Similar Events	X

 

    Page 26 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility

	Provide Approval and Follow-up on each Serious Adverse Event (SAE)	X
	Analysis of Similar Events (AOSE) (US SUSARs only)	X
	Safety Management Maintenance	X
	Maintain and Update the Safety Management Plan as Necessary to Define Roles and Responsibilities of the Sponsor and Worldwide and Describe the Procedures for the Management, Processing, and Reporting of Serious Adverse Events (SAE) and Pregnancies	X
	 Review and Incorporate Updated Comments	X
	Approve Updates 	X
	Preparation of Line Listings (LL)	X
	Prepare and Write the Line Listings and Annual Safety Reports	X
	Review and Incorporate Comments	X
	Approve Updates 	X
	Suspected Unexpected Serious Adverse Reaction (SUSAR)/ Annual Safety Reports (ASR)/ Line Listings (LL) submission to Investigators	X
	Arrange for the Timely Submission of Pharmacovigilance Documents to Relevant Investigators to Ensure Regulatory Compliance	X
	DSUR Preparation (Writing and Compiling)	X
	Pharmacovigilance Closeout	X
	Arrange for the Preparation of Pharmacovigilance Data Stored in Argus to be Transferred to the Sponsor	X
	Deliver Data Safety Monitoring Board (DSMB) Database & Tables, Figures & Listings (TFLs)	X
	DSMB Statistical Analysis Plan (SAP)	X
	DSMB Unique Tables	X
	Create Unique Study Tables (One Draft)	X
	Validate Unique Study Tables	X
	Finalize Unique Study Tables After Sponsor Review	X
	Validate Final Unique Study Tables	X
	DSMB Repeat Tables	X
	Create Repeat Study Tables (One Draft Post Database Lock)	X
	Validate Repeat Study Tables	X
	Finalize Repeat Study Tables After Sponsor Review	X
	Validate Final Repeat Study Tables	X
	DSMB Unique Listings	X
	Create Unique Study Listings (One Draft Post Database Lock)	X
	Validate Unique Study Tables	X
	Finalize Unique Study Listings After Sponsor Review	X
	Validate Final Unique Study Listings	X
	DSMB Unique Figures	X
	Create Unique Study Figures (One Draft Post Database Lock)	X
	Validate Unique Study Figures	X
	Finalize Unique Study Figures After Sponsor Review	X
	Validate Final Unique Study Figures	X

 

    Page 27 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's

 Responsibility
	DSMB Repeat Figures	X
	Create Repeat Study Figures (One Draft Post Database Lock)	X
	Validate Repeat Study Figures	X
	Finalize Repeat Study Figures After Sponsor Review	X
	Validate Final Repeat Study Figures	X
	Medical Planning	X
	Review the Protocol and Investigator Brochure to Gain an Understanding of the Trial	X
	Prepare Medical Monitoring Plan	X
	Provide Additional Study Document Review and Comment 	X
	Prepare and Conduct Clinical Research Associates (CRA) Training	X
	Communicate with Vendors to Determine Specifications Documents (Normal Ranges, Alerts Set-up, etc.)	X
	Medical Management	X
	Communicate with Sites/ Clinical Research Associates/ Project Team/ Sponsor on Protocol-medical Issues	X
	Document and Log Discussions	X
	Review Protocol Deviation Log	X
	Eligibility Review	X
	Review Selected Screening Datasets for Prospective Assessment of Eligibility	X
	Develop Subject Eligibility Form	X
	Discuss Process Design	X
	Listings Reviews	X
	Provide Adverse Events (AE), Serious Adverse Events (SAE), Medical History, Concomitant Medications, Vital Signs, Demographics Listings Review. Assumes One Cycle.	X
	Coded Data Review	X
	Provide Medical Review of Non-direct Hits for Medical Coding of Adverse Events, Concomitant Medications and Medical History	X
	Ongoing Safety Reviews of Labs and ECG Alerts	X
	Review Predefined Lab and Electrocardiogram Alerts	X
	Follow Up with Sites as Needed	X
	Maintain Medical Monitor Log	X
	Data Management Plan	X
	Prepare Data Management File and Filing of Trial Master File Documents	X
	Draft Data Management Plan for Sponsor Approval	X
	Training	X
	Electronic Case Report Form (eCRF) Development	X
	Create Database/ Electronic Data Capture (EDC)/ Electronic Case Report Form (eCRF)Specifications	X
	Electronic Case Report Form (eCRF) Completion Guidelines	X
	Draft Electronic Case Report Form Completion Guidelines and Electronic Data Capture Training Manuals for Sponsor Approval	X
	Edit Check Specifications	X

 

    Page 28 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Specify Electronic, Manual and Statistical Analysis Software (SAS) Data Validation Checks	X
	Manual Listings Creation	X
	User Acceptance Testing	X
	Define Electronic Data Capture (EDC) Roles and Responsibilities (Study Attributes)	X
	Build and Validate Data Management Database	X
	Conduct User Acceptance Testing of Database	X
	Program and Validate Electronic, Manual and SAS Data Validation Checks	X
	Set-up of Standard Reports	X
	Provide Specification, Creation and Running of Data Management Reports	X
	User Manual Development	X
	Electronic Data Capture (EDC) Support	X
	Manage Access to Study-specific Electronic Data Capture (EDC)	X
	Train Users on EDC	X
	Provide Site Support (Access and eCRF Questions)	X
	Serious Adverse Event (SAE) Reconciliation	X
	Program and Validate SAE Reconciliation Program	X
	Serious Adverse Event (SAE) Reconciliation Maintenance	X
	Run SAE Reconciliation Program	X
	Resolve Issues that Arise from SAE Reconciliation	X
	Data Cleaning	X
	Provide Data Cleaning and Listing Review	X
	Reconcile Database and Clean Local Lab Normal Ranges	X
	Manual Listing Review	X
	Vendor Reconciliation Set-up	X
	Draft Data Transfer Agreement	X
	Programming and Validation of Reconciliation Program	X
	User Acceptance Testing of Reconciliation Process	X
	Vendor Reconciliation Maintenance	X
	Upon Receipt of Data for Reconciliation, Run Reconciliation Programs	X
	Resolve Issues that Arise from Reconciliation with Vendors	X
	Vendor Integration Set-up	X
	Draft Data Transfer Agreement	X
	Program and Validate Integration Program	X
	Conduct User Acceptance Testing of Integration Process	X
	Upon Receipt of Data for Integration, Run Integration Programs	X
	Resolve Issues that Arise from Integration with Vendors	X
	Vendor Integration Maintenance	X
	Upon Receipt of Data for Reconciliation, Run Reconciliation Programs	X
	Resolve Issues that Arise from Integrations	X
	MedDRA Coding (via Coding Tool within EDC)	X
	Provide Medical Coding and Raise Appropriate Queries	X
	Manage Dictionary	X

 

    Page 29 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's

 Responsibility
	WHODRUG Coding (via Coding Tool within EDC)	X
	Provide Medical Coding and Raise Appropriate Queries	X
	Manage Dictionary	X
	Coding Dictionary Updates	X
	Data Transfer Set-up	X
	Create Data Transfer Programs and Transfer of Data During the Course of the Study	X
	Data Transfers	X
	Database Lock	X
	Conduct Database Quality Assessments	X
	Provide Data Report	X
	Create Database Lock Authorization Form	X
	Lock Database	X
	Provide Database Lock Report	X
	Conduct Final Data Transfer of Raw Data	X
	Distribute PDFs of Electronic Case Report Forms (eCRF) to the Sites and Sponsor for Archiving	X
	Archive CDs	X
	Randomization/ Kit list/ Interactive Response Technologies Review	X
	Create Randomization Specification	X
	Create and Validate One Dummy Randomization	X
	Create and Validate One Final Randomization	X
	Data Management Specifications	X
	Review One Draft of the Data Management Deliverables (eCRFs, Edit Checks, Database Set-up) for Appropriate and Necessary Data Collection with a Focus Towards Study Objectives and Endpoints	X
	Statistical Analysis Plan & Mock Shells	X
	Create One Draft Statistical Analysis Plan (SAP), Formatted, to be Inserted Directly into the Methods Section of an ICH-E3 Compliant Clinical Study Report	X
	Create One Draft of Table and Listing Shells for Each Unique Table and Listing	X
	Quality Control Draft Statistical Analysis Plan (SAP) and Table and Listing shells	X
	Create Final Statistical Analysis Plan (SAP) and Final Table and Listing Shells	X
	Study Data Tabulation Model (SDTM) Datasets	X
	Provide Study Data Tabulation Model (SDTM) Datasets from Raw Data Files Provided by the Data Management Team in Accordance with the Clinical Data Interchange Standards Consortium (CDISC) Implementation Guide and Worldwide's Standards (If Sponsor-specific Standards are Required Information Should be Provided at the Beginning of the Project)	X
	Create Dataset Specifications Document	X
	Create One Draft Version of SDTM Datasets	X

 

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	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Validate Draft Version of SDTM Datasets via Independent Quality Control and Open CDISC	X
	Create One Final Version of SDTM Datasets	X
	Validate Final Version of SDTM Datasets via Independent Quality Control and Open CDISC	X
	Analysis Datasets	X
	Provide Analysis Data Model (ADaM) Datasets (Or Derived Datasets) Based on SDTM Data,  Implementation Guide and Worldwide's Standards (If Sponsor-specific Standards are Required Information Should be Provided at Project Outset)	X
	Create Dataset Specifications Document	X
	Create One Draft Version of ADaM Datasets	X
	Validate Draft Version of ADaM Datasets via Independent Quality Control	X
	Create One Final Version of ADaM Datasets	X
	Validate Final Version of ADaM Datasets via Independent Quality Control	X
	Define.xml and Data Reviewers Guide for SDTM, Annotated CRF	X
	Create One Draft and One Final “Define.xml” Document for SDTM Datasets	X
	Create One Draft and One Final “Define.xml” Document for ADaM Datasets	X
	Create One Draft and One Final Annotated CRF, Annotated with the Variables in the SDTM Datasets	X
	Create One Draft and One Final Study Data Reviewers Guide, Adding Further Detail to the SDTM Datasets	X
	Create One Draft and One Final Analysis Data Reviewers Guide, Adding Further Detail to the ADaM Datasets	X
	Deliver Final Database & Table, Figures & Listings	X
	Final Unique Study Tables	X
	Create Unique Study Tables (One Draft Post Database Lock)	X
	Validate Unique Study Tables	X
	Finalize Unique Study Tables After Sponsor Review	X
	Validate Final Unique Study Tables	X
	Final Repeat Study Tables	X
	Create Repeat Study Tables (One Draft Post Database Lock)	X
	Validate Repeat Study Tables	X
	Finalize Repeat Study Tables After Sponsor Review	X
	Validate Final Repeat Study Tables	X
	Final Unique Study Listings	X
	Create Unique Study Listings (One Draft Post Database Lock)	X
	Validate Unique Study Listings	X
	Finalize Unique Study Listings After Sponsor Review	X
	Validate Final Unique Study Listings	X
	Final Unique Study Figures	X
	Create Unique Study Figures (One Draft Post Database Lock)	X
	Validate Unique Study Figures	X

 

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	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Finalize Unique Study Figures After Sponsor Review	X
	Validate Final Unique Study Figures	X
	Final Repeat Study Figures	X
	Create Repeat Study Figures (One Draft Post Database Lock)	X
	Validate Repeat Study Figures	X
	Finalize Repeat Study Figures After Sponsor Review	X
	Validate Final Repeat Study Figures	X
	Statistical Input to Clinical Study Report (CSR)	X
	Delivery Dry Run Database & Table, Figures & Listings	X
	Model Inform Consent Form(s) (ICF(s))	X
	Obtain Final Protocol	X
	Establish Template to be Utilized	X
	Generate First Draft for Sponsor Review	X
	Generate Second Draft for Sponsor Approval	X
	Deliver Final Model Informed Consent Form	X
	Scale Identification and Acquisition	X
	Contact Copyright Holder to Identify/ Acquire Scales (Including Translated Versions as Applicable)	X
	Approve Correct Scales Acquired	X
	Coordinate with Contracts to Obtain Scales	X
	Creation of Source Documents	X
	Apply Header/ Footer to Scales	X
	Coordinate with Regulatory for Ethics Committees/ Institutional Review Board Submission	X
	Approve Source Documents	X
	Make Scales Available for Use by Sites	X
	Approve Scales	X
	Rater Training Plan	X
	Develop Rater Training Plan (Methodology, Experience Requirements)	X
	Approve Rater Training Plan	X
	File Rater Training Plan into Trial Master File	X
	Develop Rater Training Database/ Tracker	X
	Create Rater Experience Qualification (Survey)	X
	Rater Experience Verification	X
	Work with Project Team to Develop Process for Obtaining Potential Site Raters to Complete Rater Experience Qualification (Survey)	X
	Distribute Rater Experience Qualification (Survey)	X
	Collect Rater Experience Qualification (Survey) from Sites	X
	Review Rater Experience against Rater Training Plan	X
	Recommend Next Steps for Proposed Raters Who do Not Meet Sponsor-agreed-Qualifications	X
	Approve Raters for Study Who do Not Meet Sponsor-agreed Qualifications (Overrides)	X
	File Rater Experience Qualification (Survey) Forms into the Trial Master File	X
	Rater Training and Certification	X

 

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	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Track/ Manage Raters at Each Site	X
	Process Investigator Meeting Raters for Training/ Certification	X
	Process New Raters for Training/ Certification throughout the study	X
	Follow Up with Raters to Complete Training/ Certification	X
	Issue Training/ Certification Certificates	X
	File Training/ Certification Certificates into the Trial Master File	X
	Applied Skill Assessment (ASA) not at Investigator Meeting	X
	Instructions for Site Raters on How to Submit Applied Skills Assessment (ASA) to Worldwide	X
	Clinical Review and Feedback for Applied Skills Assessment (ASA)	X
	Complete Applied Skills Assessment Form (For Each Rater's ASA)	X
	File Applied Skills Assessment Form into the Trial Master File	X
	Coordinate Next Steps with Sponsor when Rater Fails the Applied Skills Assessment	X
	Didactic Presentation	X
	Develop Didactics for the Study	X
	Approve Didactics	X
	Web Portal	X
	Define Requirements for Study Web Portal	X
	Provide Training Materials to be Uploaded to the Web Portal	X
	Develop/ Configure Study Web Portal	X
	User Acceptance Test Study Web Portal	X
	Data Surveillance Plan	X
	Develop Data Surveillance Plan (Methodology)	X
	Approve Data Surveillance Plan	X
	Develop Source Document Review Database/ Tracker	X
	Develop EDC Monitoring Database/ Tracker	X
	Set-up of Clinical Assessment Technologies EDC Data Monitoring System	X
	Provide Data Management with Flags to be Programmed into EDC/ SAS	X
	Develop and Test EDC/ SAS Flags	X
	Define Requirements for EDC Monitoring Reports	X
	Develop and Test EDC Monitoring Reports	X
	Clinical Assessment Technologies Data Management Reports	X
	Electronic Data Capture (EDC) Flag Clinical Review	X
	Provide Clinical Review of Flagged Subject Visits	X
	Collection & Review of Source Documents	X
	Document Interactive Response Technology Notifications in Source Document Database/ Tracker	X
	Collect Source Documents from Sites for Clinical Review	X
	Follow Up with Sites for Missing (Not Submitted) Source Documents	X
	Review Clinical Source Documents	X
	Clinical Assessment Start-up & Planning	X

 

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	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Clinical Assessment Maintenance & Reporting	X
	Clinical Assessment Technologies Virtual Training Session 	X
	Confirm Attendees and Communication Details	X
	Create and Distribute Invitation to Attend Training Sessions	X
	Conduct Virtual Training Sessions	X
	Close Out Virtual Training Sessions (Document Attendees, Distribute Training Certificates)	X
	Pre go-live Project Management, Requirements Gathering & Design (SaaS)	X
	Lead Interactive Response Technology-focused Gathering Meetings	X
	Write User Requirements Specifications According to Protocol Design	X
	Write Interactive Response Technology Project Plan	X
	Configuration/Coding (SaaS)	X
	Configure Interactive Response Technology System for Study According to Specifications	X
	Write Custom Code if Required	X
	Validation (SaaS)	X
	Develop Test Plan	X
	Perform Testing of System Against Specifications	X
	Review testing materials	X
	Review and Sign Test Plan	X
	Review and Sign Test Summary Report (Including a Review of any Defects)	X
	Systems Integrations (SaaS)	X
	Manage the Set-up of Any Integrations Between Interactive Response Technology and Other Systems 	X
	Coordinate Data Transfers	X
	Configure and Test Integration	X
	Sponsor User Acceptance Testing (SaaS)	X
	Set Up Data for User Acceptance Testing	X
	Facilitate the Performance of User Acceptance Testing for the Sponsor	X
	Interactive Response Technologies Inventory Implementation and Review	X
	Interactive Response Technology Project Management (SaaS)	X
	Oversight and Accountability for the Project	X
	Act as Point of Escalation for Any Interactive Response Technology-related Issues for the Study	X
	Production Support (SaaS)	X
	Daily Support of Interactive Response Technology	X
	Production Randomization Monitoring and Audit	X
	Monitoring Patient and Material Randomization to Ensure Correct Execution in Production	X
	Decommissioning (SaaS)	X

 

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	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Coordinate Decommissioning of the System and Data Archiving at End of Study	X
	Clinical Trial Management System (CTMS) Set-up	X
	Develop User Requirement Specifications	X
	Monitoring Visit Report (MVR) Review and Configuration	X
	CTMS OnPoint and SharePoint Build/ Configuration	X
	CTMS OnPoint and SharePoint User Acceptance Testing	X
	Create Study-specific Guides	X
	Create System Alerts	X
	Develop Sponsor Training Slides	X
	Create Study Specific Access Form	X
	Submit Documents to the eTMF as required	X
	Conduct Study Team Q&A Session	X
	Conduct Sponsor Training	X
	Clinical Trial Management System Helpdesk/ Maintenance	X
	Administer Required Training	X
	Grant CTMS User and Study Access	X
	Respond to CTMS service desk requests	X
	Support MVR Issues and Changes	X
	Edge Payments Customization	X
	Edge Payments Maintenance, Support, Changes	X
	Grant System Access	X
	Respond to Helpdesk Queries	X
	Add Sites	X
	Edge Payments Maintenance, Support, Changes	X
	Rater Web Portal Set-up	X
	Rater Web Portal Maintenance, Support, Changes	X
	Create Study Specific Integration documents for Interactive Response Technologies to EDC	X
	Create Study Specific Integration documents for EDC to OnPoint CTMS	X
	Integration Set-up	X
	Project Management - Start-up	X
	Identify Sites/ Principal Investigators 	X
	Create or Review Project Plans	X
	Execute Project Plans	X
	Prepare for and Plan Site Training	X
	Provide and Receive Project-specific Training (Develop Training, Presenting, Receive Training, Includes Protocol Review Time)	X
	Set Up Internal/ External Systems	X
	Review Sponsor Standard Operating Procedures	X
	Review Scope of Work and Finalize Study Specifications	X
	Develop Project Timelines	X
	Prepare for and Attend Internal and External Meetings and Calls Including Agenda/ Minute Preparation	X
	Prepare and Distribute Study Newsletters and Other Site Communications	X

 

    Page 35 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's 

Responsibility
	Maintain and Quality Control Trial Master File (Including Response to Internal or Sponsor Audits) and Deliver to Sponsor	X
	Manage Study Vendors (Includes Identification, Selection, Contract Negotiation and Management)	X
	Complete all Project-related Internal System Data Entry such as Time Entry, Monthly Operational Reviews, Resource Planning, Financial Tracking or Other Internal Systems	X
	Prepare Site/ Study Documents (Site Reference Material, Study Binders, Recruitment Tools)	X
	Manage Site Supplies	X
	Manage Site Grant and Principal Investigator Reimbursement Payments (Includes Initiating Grant Fund Replenishment Invoicing Requests and Approval of Payments)	X
	Complete Revenue Reporting and Projections	X
	Manage Changes to Contracts	X
	Procure Invoice Approval (Includes Follow-up Internally or with Sponsor	X
	Manage Vendor Payments	X
	Complete Financial Reconciliation	X
	Monitor, Evaluate and Adjust Key Performance Indicators	X
	Generate Status Reports	X
	Track Project-related Data to Facilitate and Inform Status Reporting and Study Management	X
	Project Management - Conduct	X
	Oversee Patient Recruitment	X
	Prepare for and Plan Investigator Meeting (For Those Occurring after Start-up)	X
	Participate in and Present at Investigator Meeting (For Those Occurring after Start-up)	X
	Oversee the Management, Monitoring, Adjustment and Ongoing Revision of Project Plans (Updates to Study Plans, Review of Risks and Identification of New Mitigation Strategies)	X
	Provide and Receive Project-specific Training (Develop Training, Presenting, Receive Training, Includes Protocol Review Time)	X
	Oversee Changes to Internal/ External Systems	X
	Revise Project Timelines	X
	Prepare for and Attend Internal and External Meetings and Calls including Agenda/ Minute Preparation	X
	Prepare and Distribute Study Newsletters and Other Site Communications	X
	Maintain and Quality Control Trial Master File (Including Response to Internal or Sponsor Audits) and Deliver to Sponsor	X
	Manage Study Vendors (Includes Identification, Selection, Contract Negotiation and Management)	X
	Complete all Project-related Internal System Data Entry such as Time Entry, Monthly Operational Reviews, Resource Planning, Financial Tracking or Other Internal Systems	X

 

    Page 36 of 47

     

    

 

	Worldwide Clinical Trials Responsibility Matrix
	Task	Worldwide's

 Responsibility
	Prepare Site/ Study Documents (Site Reference Material, Study Binders, Recruitment Tools)	X
	Manage Site Supplies	X
	Manage Site Grant and Principal Investigator Reimbursement Payments (Includes Initiating Grant Fund Replenishment Invoicing Requests and Approval of Payments)	X
	Complete Revenue Reporting and Projections	X
	Manage Changes to Contracts	X
	Procure Invoice Approval (Includes Follow-up Internally or with Sponsor	X
	Manage Vendor Payments	X
	Complete Financial Reconciliation	X
	Monitor, Evaluate and Adjust Key Performance Indicators	X
	Generate Status Reports	X
	Track Project-related Data to Facilitate and Inform Status Reporting and Study Management	X
	Project Management - Close-out	X
	Oversee the final management, monitoring, adjustment and ongoing revision of project plans	X
	Provide and receive Project Specific Training (develop training, presenting, receive training)	X
	Revise Project Timelines	X
	Prepare for and attend Internal and External Meetings and Calls including Agenda/Minute Preparation	X
	Prepare and Distribute Site Communications	X
	Maintain and Quality Control Trial Master File (Including Response to Internal or Sponsor Audits) and Deliver to Sponsor	X
	Manage Study Vendors 	X
	Complete all Project-related Internal System Data Entry 	X
	Prepare Site/ Study Documents 	X
	Manage Site Supplies	X
	Manage Site Grant and Principal Investigator Reimbursement Payments 	X
	Complete Revenue Reporting and Projections	X
	Manage Changes to Contracts	X
	Procure Invoice Approval (Includes Follow-up Internally or with Sponsor	X
	Manage Vendor Payments	X
	Complete Financial Reconciliation	X
	Monitor, Evaluate and Adjust Key Performance Indicators	X
	Generate Status Reports	X
	Track Project-related Data to Facilitate and Inform Status Reporting and Study Management	X

 

    Page 37 of 47

     

    

 

 

EXHIBIT B

TIMELINE

 

	Study Timeline	Estimated Start Date	Estimated End Date	Duration (Months)
	Commencement of Work (Start Date)	20-Apr-2020	 	 
	Protocol Finalized	1-Jun-2020	 	 
	Study Start-up	20-Apr-2020	27-Sep-2020	5.3
	Patient Enrollment Period	28-Sep-2020	14-Sep-2021	11.6
	Patient Active Treatment	15-Sep-2021	3-Oct-2022	12.6
	Patient Follow-up Phase	4-Oct-2022	4-Oct-2022	0.0
	Last eCRF Submitted to Data Management	5-Oct-2022	2-Nov-2022	1.0
	Database Lock	3-Nov-2022	15-Nov-2022	0.4
	Final Tables, Listings, Figures/Graphs	16-Nov-2022	5-Jan-2023	1.7
	Final Clinical Study Report	6-Jan-2023	13-Mar-2023	2.2
	Total Study Duration (Months)	 	 	34.6

 

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EXHIBIT C

BUDGET

 

	 	 	 	 
	 	 	 	Service Agreement Budget
	Services	Unit	# Units	Unit Cost 

USD	Total Cost USD
	Site Activation	 	 	 	 
	o	Feasibility/ Site Identification	Site	15.00	784.00	11,760.00
	o	Site Activation Lead Planning Per Country	Country	1.00	2,268.00	2,268.00
	o	Site Activation Lead Oversight - Start Up Phase	Site Months	106.00	226.80	24,040.80
	o	Site Activation Lead Oversight - Conduct Phase	Site Months	510.00	98.60	50,286.24
	o	Trial Master File (TMF) Filing & QC	Site/Quarter	196.00	311.24	61,002.86
	o	Regulatory Project Plan	Plan	1.00	2,270.00	2,270.00
	o	Regulatory Set-up	Study	1.00	3,450.00	3,450.00
	o	Regulatory Tracking & Follow-up	Country/Month	31.00	151.55	4,698.05
	o	Core Documents Master Templates	Study	1.00	3,995.00	3,995.00
	o	Essential Documents & Review (US)	Site	20.00	2,513.50	50,270.00
	o	Essential Documents Review Plan	Plan	1.00	2,334.00	2,334.00
	o	Essential Documents Checklist	Country	1.00	131.50	131.50
	o	Investigator Agreements 	CTA	20.00	1,644.75	32,895.00
	o	Investigator Agreements Country Specific Templates	Country Template	1.00	1,352.00	1,352.00
	o	Contract and Budget Plan (CBP)	Plan	1.00	985.00	985.00
	o	Investigator Grant Build	Build	1.00	2,750.00	2,750.00
	o	Submission Strategy & Risk Assessment	Country	1.00	1,393.00	1,393.00
	o	Central Institutional Review Board (IRB) Site Submissions (US)	Site	20.00	667.00	13,340.00
	o	Central Institutional Review Board (IRB) Submission, Study Level (US)	Study	1.00	944.00	944.00
	o	Central IRB Site Submissions (US)- Yearly Maintenance	Site/Year	58.00	314.00	18,212.00
	o	Central IRB Submissions (Study Level)- Yearly Maintenance	Study/Year	3.00	236.00	708.00
	o	Central IRB Site Submissions (US)- End of Trial Notifications	Site	20.00	157.00	3,140.00
	o	Central IRB Submissions (Study Level)- End of Trial Notifications	Study	1.00	59.00	59.00
	o	Master Informed Consent Form (ICF) Review	ICF	3.00	1,816.00	5,448.00
	o	Translation Coordination	Language	1.00	1,416.00	1,416.00
	 	Sub-Total Study Site Activation	 	 	 	299,148.45
	Trial Master File	 	 	 	 
	o	TMF Management Plan & TMF Risk Assessment	Plan	1.00	700.00	700.00
	o	Worldwide TMF: TMF Set-up: Pre Site Activation Activities	Sites	20.00	525.00	10,500.00
	o	Worldwide TMF: TMF Maintenance & QC	Site Months	623.00	56.49	35,192.66
	o	Worldwide TMF: TMF Final Reconciliation & Transfer	Sites	20.00	379.57	7,591.32
	 	Sub-Total Trial Master File	 	 	 	53,983.98

 

    Page 39 of 47

     

    

 

	 	 	 	Service Agreement Budget
	 	Services	Unit	# Units	Unit Cost 

USD	Total Cost USD
	Project Meetings	 	 	 	 

	o	Internal Alignment (KO) Meeting	Meeting	1.00	14,628.00	14,628.00
	o	Sponsor Alignment (KO) Meeting	Meeting	1.00	15,681.00	15,681.00
	o	Webex Trainings	Meeting	2.00	1,385.00	2,770.00
	o	Sponsor Teleconferences	Teleconferences	82.00	1,098.17	90,050.02
	o	Internal Teleconferences	Teleconferences	82.00	1,098.17	90,050.02
	 	Sub-Total Project Meetings	 	 	 	213,179.04
	Clinical Monitoring	 	 	 	 
	o	Lead Clinical Research Associate Support	Month	33.00	12,101.75	399,357.69
	o	Site Management	Site Months	530.00	595.19	315,451.58
	o	Internal Clinical Research Associate Calls & Project Communication	Month	28.00	1,013.20	28,369.62
	o	Clinical Research Associate Training (not at Investigator Meeting)	Attendee	4.00	1,478.00	5,912.00
	o	Remote Pre-site Selection Visits	Visit	10.00	1,013.00	10,130.00
	o	On-site Pre-site Selection Visits	Visit	10.00	3,283.50	32,835.00
	o	On-site Site Initiation Visits	Visit	20.00	3,675.50	73,510.00
	o	Remote Monitoring Visits Conduct 	Visit	140.00	950.92	133,129.10
	o	On-Site Monitoring Visits Conduct	Visit	140.00	4,257.43	596,040.30
	o	Additional Time On-site	Visit	80.00	820.61	65,648.69
	o	On-site Close-out Visits	Visit	20.00	4,216.46	84,329.15
	o	Remote Electronic Data Capture (EDC) Review Conduct	Site Months	390.00	181.60	70,824.60
	 	Sub Total Clinical Monitoring	 	 	 	1,815,537.73
	Grant & Vendor Payments	 	 	 	 
	o	Set-up Grant Payments	Contract	20.00	110.00	2,200.00
	o	Process Grant Payments 	Payment	480.00	66.39	31,866.78
	o	Process Site Cost Payments 	Site	20.00	55.00	1,100.00
	o	Set-up Vendor Payments	Vendor	3.00	102.00	306.00
	o	Process Vendor Payments	Month	57.00	54.34	3,097.20
	 	Sub-Total Grant & Vendor Payments	 	 	 	38,569.98
	Risk Based Quality Management	 	 	 	 
	o	Protocol Risk Assessment	Risk Assessment	1.00	14,224.58	14,224.58
	 	Sub Total Quality Assurance Audits	 	 	 	14,224.58
	Drug Safety 	 	 	 	 
	o	Database Set-up & Configuration	Database	1.00	3,640.00	3,640.00
	o	Safety Management Plan Development	Plan	1.00	3,957.00	3,957.00
	o	Safety Training (Sites, Clinical Research Associates, Project Team)	Training	1.00	1,039.50	1,039.50
	o	Serious Adverse Events (SAE) Processing, Investigation, Narrative, Approval & Query Generation 	SAE	11.00	1,693.39	18,627.29
	o	Analysis of Similar Events (AOSE) (US SUSARs only)	SUSAR Report	1.00	496.12	496.12
	o	Safety Management Maintenance	Month	32.00	1,530.63	48,980.30
	o	Preparation of Line Listings (LL)	Report	1.00	650.02	650.02

 

    Page 40 of 47

     

    

 

	 	 	 	Service Agreement Budget
	 	Services	Unit	# Units	Unit Cost 

USD	Total Cost USD

	o	Suspected Unexpected Serious Adverse Reaction (SUSAR)/ Annual Safety Reports (ASR)/ Line Listings (LL) submission to Investigators	Country * Submissions	3.00	160.63	481.88
	o	DSUR Preparation (Writing and Compiling)	DSUR	3.00	12,577.16	37,731.48
	o	Pharmacovigilance Closeout	Transfer	1.00	3,336.17	3,336.17
	 	Sub-Total Drug Safety 	 	 	 	118,939.76
	Data Safety Monitoring Board (DSMB)	 	 	 	 
	o	Deliver Data Safety Monitoring Board (DSMB) Database & Tables, Figures & Listings (TFLs)	 Delivery 	2.00	22,667.24	45,334.48
	 	DSMB Statistical Analysis Plan (SAP)	 Plan 	1.00	11,770.88	11,698.28
	 	DSMB Unique Tables	 Unique Table 	5.00	1,534.49	7,672.43
	 	DSMB Repeat Tables	 Repeat Table 	18.00	604.87	10,887.73
	 	DSMB Unique Listings	 Unique Listing 	11.00	938.77	10,326.51
	 	DSMB Unique Figures	 Unique Figure 	5.00	2,816.32	14,081.61
	 	DSMB Repeat Figures	 Repeat Figure 	5.00	930.77	4,653.86
	 	Sub-Total Data Safety Monitoring Board 	 	 	 	104,654.90
	Medical Monitoring	 	 	 	 
	o	Medical Planning	Month	1.00	23,050.00	23,050.00
	o	Medical Management	Screened Subject	220.00	215.88	47,492.90
	o	Eligibility Review	Screened Subject	220.00	479.73	105,539.78
	o	Listings Reviews	Enrolled Subject	100.00	119.93	11,993.16
	o	Coded Data Review	Enrolled Subject	100.00	19.19	1,919.11
	o	Ongoing Safety Reviews of Labs and ECG Alerts	Alert	318.00	167.91	53,396.71
	o	Maintain Medical Monitor Log	Month	24.00	1,144.69	27,472.66
	 	Sub-Total Medical Monitoring	 	 	 	270,864.32
	Data Management	 	 	 	 
	o	Data Management Plan	Plan	1.00	3,474.00	3,474.00
	o	Training	Study	1.00	3,264.00	3,264.00
	o	Electronic Case Report Form (eCRF) Development	Unique Pages	30.00	601.65	18,049.50
	o	Electronic Case Report Form (eCRF) Completion Guidelines	Database	1.00	3,088.00	3,088.00
	o	Edit Check Specifications	Edit Check	240.00	80.31	19,274.40
	o	Manual Listings Creation	Listing	30.00	959.00	28,770.00
	o	User Acceptance Testing	Database	1.00	7,720.00	7,720.00
	o	Set-up of Standard Reports	Study	1.00	7,672.00	7,672.00
	o	User Manual Development	Study	1.00	1,544.00	1,544.00
	o	Electronic Data Capture (EDC) Support	Users	60.00	128.33	7,699.86
	o	Serious Adverse Event (SAE) Reconciliation	SAE	11.00	193.00	2,123.00
	o	Serious Adverse Event (SAE) Reconciliation Maintenance	Months	26.00	99.64	2,590.65
	o	Data Cleaning	Total Pages	23,565.00	1.24	29,204.50
	o	Manual Listing Review	Listings	780.00	100.69	78,538.32

 

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	 	 	 	Service Agreement Budget
	 	Services	Unit	# Units	Unit Cost 

USD	Total Cost USD

	o	Vendor Reconciliation Set-up	Vendor	2.00	3,072.00	6,144.00
	o	Vendor Reconciliation Maintenance	Upload	51.00	586.90	29,931.82
	o	Vendor Integration Set-up	Integration	1.00	3,446.00	3,446.00
	o	Vendor Integration Maintenance	Upload	26.00	586.90	15,259.37
	o	MedDRA Coding (via Coding Tool within EDC)	Terms	1,000.00	4.03	4,032.41
	o	WHODRUG Coding (via Coding Tool within EDC)	Meds	1,500.00	8.05	12,082.22
	o	Coding Dictionary Updates	Year	2.00	1,610.97	3,221.93
	o	Data Transfer Set-up	Database	1.00	384.00	384.00
	o	Data Transfers	Transfer	9.00	400.66	3,605.90
	o	Database Lock	Database Lock	1.00	7,801.85	7,801.85
	o	Archive CDs	Site	20.00	86.13	1,722.51
	o	Data Management Coordination	Month	31.00	1,610.97	49,940.15
	 	Sub-Total Data Management	 	 	 	350,584.39
	Biostatistics	 	 	 	 
	o	Randomization/ Kit list/ Interactive Response Technologies Review	 List 	2.00	6,024.00	12,048.00
	o	Data Management Specifications	 Protocol 	1.00	6,574.55	6,574.55
	o	Statistical Analysis Plan & Mock Shells	 Plan 	1.00	17,893.58	17,893.58
	o	Study Data Tabulation Model (SDTM) Datasets	 Dataset 	25.00	2,688.39	67,209.84
	o	Analysis Datasets	 Dataset 	15.00	3,353.40	50,300.93
	o	Define.xml and Data Reviewers Guide for SDTM, Annotated CRF	 Specification 	5.00	5,084.93	25,424.65
	o	Deliver Final Database & Table, Figures & Listings	 Delivery 	1.00	7,643.93	7,643.93
	 	Final Unique Study Tables	 Unique Table 	25.00	1,544.01	38,600.23
	 	Final Repeat Study Tables	 Repeat Table 	50.00	608.63	30,431.36
	 	Final Unique Study Listings	 Unique Listing 	25.00	944.60	23,614.97
	 	Final Unique Study Figures	 Unique Figure 	10.00	2,833.80	28,337.97
	 	Final Repeat Study Figures	 Repeat Figure 	10.00	936.55	9,365.46
	o	Statistical Input to Clinical Study Report (CSR)	 CSR 	1.00	6,425.06	6,425.06
	o	Delivery Dry Run Database & Table, Figures & Listings	 Delivery 	1.00	15,315.15	15,315.15
	 	Sub-Total Biostatistics	 	 	 	339,185.68
	Medical Writing	 	 	 	 
	o	Model Inform Consent Form(s) (ICF(s))	ICF(s)	3.00	8,204.00	24,612.00
	 	Sub-Total Medical Writing	 	 	 	24,612.00
	Clinical Assessment Technologies	 	 	 	 
	o	Scale Identification and Acquisition	 Scale 	6.00	1,029.00	6,174.00
	o	Creation of Source Documents	 Language* Scale 	12.00	429.63	5,155.50
	o	Rater Training Plan	 Plan 	1.00	2,805.00	2,805.00
	o	Rater Experience Verification	 Rater 	43.00	96.75	4,160.25
	o	Rater Training and Certification	 Rater 	34.00	182.50	6,205.00

 

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	 	 	 	Service Agreement Budget
	 	Services	Unit	# Units	Unit Cost 

USD	Total Cost USD

	o	Applied Skill Assessment (ASA) not at Investigator Meeting	 ASA*Rater 	34.00	275.88	9,379.75
	o	Didactic Presentation	 Presentation  	1.00	1,438.38	1,438.38
	o	Web Portal	 Portal 	1.00	6,043.10	6,043.10
	o	Data Surveillance Plan	 Plan 	1.00	13,985.50	13,985.50
	o	Set-up of Clinical Assessment Technologies EDC Data Monitoring System	 System 	1.00	9,837.50	9,837.50
	o	Clinical Assessment Technologies Data Management Reports	 Month 	24.00	398.57	9,565.71
	o	Electronic Data Capture (EDC) Flag Clinical Review	 Visit 	384.00	215.41	82,715.84
	o	Collection & Review of Source Documents	 Visit * Scale 	244.00	151.25	36,905.00
	o	Clinical Assessment Start-up & Planning	 Month 	5.00	1,798.25	8,991.25
	o	Clinical Assessment Maintenance & Reporting	 Month 	24.00	938.13	22,515.01
	o	Clinical Assessment Technologies Virtual Training Session 	 WebEx 	2.00	6,306.00	12,612.00
	 	Sub-Total Clinical Assessment Technologies	 	 	 	238,488.79
	Interactive Response Technology	 	 	 	 
	o	Pre go-live Project Management, Requirements Gathering & Design (SaaS)	Build	1.00	15,484.00	15,484.00
	o	Configuration/Coding (SaaS)	Build	1.00	5,856.00	5,856.00
	o	Validation (SaaS)	Build	1.00	8,928.00	8,928.00
	o	Review testing materials	Build	1.00	996.00	996.00
	o	Systems Integrations (SaaS)	Build	1.00	15,680.50	15,680.50
	o	Sponsor User Acceptance Testing (SaaS)	Build	1.00	10,368.00	10,368.00
	o	Interactive Response Technologies Inventory Implementation and Review	Build	1.00	1,732.00	1,732.00
	o	Interactive Response Technology Project Management (SaaS)	Month	26.00	3,443.50	89,530.88
	o	Production Support (SaaS)	Month	26.00	4,732.71	123,050.37
	o	Production Randomization Monitoring and Audit	System	1.00	3,662.73	3,662.73
	o	Decommissioning (SaaS)	System	1.00	2,197.64	2,197.64
	 	Sub-Total Interactive Response Technology	 	 	 	277,486.12
	Technology	 	 	 	 
	o	Clinical Trial Management System (CTMS) Set-up	System	1.00	10,927.00	10,927.00
	o	Clinical Trial Management System Helpdesk/ Maintenance	Month	35.00	892.08	31,222.89
	o	Edge Payments Set-up: Grant Payments	System	1.00	2,848.00	2,848.00
	o	Edge Payments Customization	System	1.00	4,895.00	4,895.00
	o	Edge Payments Maintenance, Support, Changes	Month	24.00	278.58	6,685.89
	o	Rater Web Portal Set-up	System	1.00	19,353.00	19,353.00
	o	Rater Web Portal Maintenance, Support, Changes	Month	29.00	536.29	15,552.44

 

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	 	 	 	Service Agreement Budget
	 	Services	Unit	# Units	Unit Cost 

USD	Total Cost USD

	o	Integration Set-up	System	1.00	36,093.00	36,093.00
	o	Integration Maintenance, Support, Changes	Month	29.00	406.92	11,800.68
	 	Sub-Total Technology	 	 	 	139,377.90
	Project Management 	 	 	 	 
	o	Project Management - Start-up	Month	5.00	22,531.57	112,657.83
	o	Project Management - Conduct	Month	24.00	19,571.52	469,716.40
	o	Project Management - Close-out	Month	5.00	16,116.23	80,581.15
	 	Sub-Total Project Management	 	 	 	662,955.38
	 	 	 	 	 	 
	 	Total Estimated Service Fees	 	 	 	4,961,793.00
	 	 	 	 	 	 
	 	Discount	 	 	 	-372,134.48
	 	 	 	 	 	 
	 	Total Estimated Service Fees including Discount	 	 	 	4,589,658.53
	 	 	 	 	 	 
	System & General Expenses	 	 	 	 
	o	IBMCD Electronic Data Capture (EDC) Maintenance & Hosting	Month	29.00	6,000.00	174,000.00
	o	Argus Safety Database Set-up & Configuration	System	1.00	15,000.00	15,000.00
	o	Argus Safety Database Hosting	Month	25.51	2,116.82	54,000.00
	o	Clinical Trial Management System User Access	System	1.00	3,000.00	3,000.00
	o	IBMCD IRT System Fees	System	1.00	14,500.00	14,500.00
	o	Electronic Trial Master File (eTMF) Monthly Hosting Fees	Site months	733.00	35.00	25,655.00
	o	Regulatory System Fees	Site	31.00	387.10	12,000.00
	Total System & General Expenses	 	 	 	298,155.00
	 	 	 	 	 	 
	Estimated Pass-through Costs	 	 	 	 
	 	 	 	 	 	 
	Study Start-up Pass-through Costs	 	 	 	 
	o	Print and Ship Investigator Site File to Sites	Site	20.00	300.00	6,000.00
	o	Institutional Review Board (IRB) Site Regulatory Documents (includes preparation, collection, annual renewals if needed)	 	 	 	 
	 	North America - Central IRB	Site	20.00	1,500.00	30,000.00
	 	Sub-Total Start-up Pass-through Costs	 	 	 	36,000.00
	Clinical Monitoring Pass-through Costs	 	 	 	 
	o	Pre-site Selection Visits	Visit	10.00	700.00	7,000.00
	o	Site Initiation Visits	Visit	20.00	700.00	14,000.00
	o	Interim Monitoring Visits	Visit	140.00	700.00	98,000.00
	o	Additional Time on Site	Visit	80.00	700.00	56,000.00
	o	Close-Out Visits	Visit	20.00	700.00	14,000.00
	o	Site Management	Site Months	530.00	10.00	5,300.00
	 	Sub Total Study Conduct Pass-through Costs	 	 	 	194,300.00

 

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	Services	Unit	 # Units	Unit Cost 

USD	Total Cost USD
	Clinical Assessment Technologies Pass-through Costs	 	 	 	 
	o	Scale Licenses	License	6.00	7,567.50	45,405.00
	o	Scale Translations	Scales* Languages	1.00	2,500.00	2,500.00
	o	Rater Experience Surveys/Trial Interactive	Raters*Surveys	10.00	10.00	100.00
	 	Sub-Total Clinical Assessment Technologies Pass-through Costs	 	 	 	48,005.00
	Archiving Pass-through Costs	 	 	 	 
	o	Shipment of Completed Case Report Forms (CRF) Back to Sites (archive copy, disc for EDC)	Shipment	20.00	50.00	1,000.00
	o	Shipment of Completed electronic Case Report Forms (eCRF)Back to Sponsor (disc )	Shipment	1.00	50.00	50.00
	 	Sub-Total Archiving Pass-through Costs	 	 	 	1,050.00
	Trial Master File Pass-through Costs	 	 	 	 
	o	Final Transfer of Study Records to Sponsor (Disk)	Transfer	1.00	150.00	150.00
	 	Sub-Total Project Management Pass-through Costs	 	 	 	150.00
	Project Management Pass-through Costs	 	 	 	 
	o	Project Management Passthrough Costs	Month	35.00	100.00	3,500.00
	 	Sub-Total Project Management Pass-through Costs	 	 	 	3,500.00
	Third Party Vendor Costs	 	 	 	 
	o	Central Lab: ACM	Study	1.00	248,814.00	248,814.00
	o	ECG Provider: ERT	Study	1.00	114,000.00	114,000.00
	o	Avantor Sciences (ballpark)	Study	1.00	40,000.00	40,000.00
	 	Sub-Total Third Party Vendors	 	 	 	402,814.00
	PI Fees	 	 	 	 	 
	o	Investigator Grants- Completed patients	Patient	85.00	37,304.00	3,170,840.00
	o	Investigator Grants- Screen failure patients	Patient	120.00	3,645.50	437,460.00
	o	Investigator Grants- Dropped patients	Patient	15.00	21,548.40	323,226.00
	o	Site Costs	Site	20.00	13,032.00	260,640.00
	 	Sub-Total PI Fees	 	 	 	4,192,166.00
	Total Estimated Pass-Through Costs	 	 	 	4,877,985.00
	 	 	 	 	 	 
	Total Estimated Budget	 	 	 	9,765,798.53
	Note that the unit costs are derived from the total cost after regional & annual rates have been applied and therefore result in a blended rate.	 

 

    Page 45 of 47

     

    

 

EXHIBIT D

PAYMENT SCHEDULE

 

1.      
Service Fees:

 

		1.1.	Notwithstanding the payment terms in Section 3.4 of the Agreement, upon signature of this Work
Order, Sponsor will pay Worldwide an advance payment of $488,781.35 due upon ten (10) days of receipt, (advance payment represents
10% of the Service Fee and System and General Expenses total). All subsequent invoices will be submitted to Sponsor by email monthly
based on units completed in the preceding month according to the Budget above, with each subsequent invoice for Service Fees and
System and General Expenses reduced by 10% until the advance payment is exhausted. With the exception of the first payment described
above in the amount of $488,781.35, payment terms shall be as defined in this Agreement. Any outstanding balances will be reconciled
at the end of the Study.

 

		1.2.	The bottom line discount (“Discount”) shall be defined as a one-time discount applied
to the service fees of this study budget, based on the current scope and specifications detailed within this Work Order. Should
these parameters vary from what is presented within, Worldwide reserves the right to adjust any discounts or commercial incentives
based on the revised scope and budget values.

 

		1.3.	Payment shall be issued by check or wire transfer at Sponsor’s option. Wiring instructions are as follows:

 

	 	Account Holder:	 	Worldwide Clinical Trials, Inc.
	 	Bank Name:	 	HSBC Bank USA, NA
	 	Bank Address:	 	445 North Bedford Dr.
	 	 	 	Beverly Hills, CA 90210
	 	ABA Routing No.:	 	021001088
	 	Bank Account No.:	 	167-74758-4
	 	Swift Code:	 	MRMDUS33
	 	Taxpayer ID#: 	 	26-0902850

 

2.      
Pass-through Expenses:

 

		2.1.	Notwithstanding the payment terms in Section 3.4 of the Agreement, Worldwide shall invoice Sponsor
an advance payment of $137,163.80 due upon ten (10) days of receipt (advance payment represents 20% of the anticipated Pass-through
Expenses). Worldwide will submit subsequent monthly invoices by email for incurred Pass-through Expenses based on actuals, with
each subsequent invoice for Pass-through Expenses reduced by 20% until the advance payment is exhausted. With the exception of
the first payment described above in the amount of $137,163.80 payment terms shall be as defined in this Agreement. Any outstanding
balances will be reconciled at the end of the Study.

 

3.      
Investigator/Institution Fees:

 

		3.1.	Notwithstanding the payment terms in Section 3.4 of the Agreement, Worldwide shall invoice Sponsor
an advance payment of $314,412.45 due upon ten (10) days of receipt (advance payment represents 7.5% of the anticipated Investigator/Institution
grants). Periodically, Worldwide will invoice Sponsor by email to replenish this advance back-up to an amount equivalent to 7.5%
of the anticipated Investigator/Institution grants or such other amount of funds needed to bring the balance to the sufficient
amount to ensure that payments are made to sites in a timely manner. The invoice will be accompanied by a report which itemizes
the Investigator/Institution grants that have been paid in the period, and will reconcile the use of funds received from Sponsor.
If an increase in the amount of anticipated Investigator/Institution grants is necessary, Worldwide will provide appropriate support
justifying such increase. Any outstanding balances will be reconciled and provided no earlier than 30 days after at the end of
the Study. For avoidance of doubt, Worldwide will make all grant payments only from funds received from Sponsor specifically for
this purpose. Worldwide shall not be liable for any payments delays due to the delay in receipt of funds from Sponsor.

 

    Page 46 of 47

     

    

 

EXHIBIT E

FORM OF CHANGE ORDER

 

	Client:
    	Worldwide
    Project Manager:
	Protocol
    Number:	Worldwide
    ID:
	Change
    Order #: 	Date:
    

 

Worldwide Clinical Trials, Inc.
(“Worldwide”) and Neurotrope Bioscience, Inc. (“Sponsor”) entered into an agreement dated [effective
date] (“Agreement”) [as amended by Change Order # 1 effective [effective date]] [and further amended by Change
Order # 2 effective [effective date]] in which Worldwide was to provide certain Services to Sponsor in connection with Study
[insert Protocol number] (“Study”). Worldwide and Sponsor wish to amend the Agreement as follows:

 

1. Revisions to the Scope of Services.
The Scope of Services has been revised as described below, and Worldwide will provide the following additional services [will
not provide the following services initially contracted]:

 

	Description
    of Service	Cost
	 	 
	 	 

 

2. Revisions to the Study Budget. As a
result of the changes to the Services and Scope of Services, this Change Order # [Insert] [increases] [decreases] the Service
fees as shown above. A revised total budget value is below.

 

	 	Services
    Fees	Estimated
    Pass Through Costs	Total
	Original
    Agreement Value:	 	 	 
	Change
    Order #1 Value:	 	 	 
	[Add
    additional Change Orders as necessary]	 	 	 
	Revised
    Contract Value:	 	 	 

 

3. Revisions to the Payment Schedule.
A revised and restated payment schedule, as amended by Change Order # [Insert#] is detailed below.

 

Payment
Schedule, as amended by Change Order # [Insert]

 

Except to the extent specifically
modified by this Change Order # [Insert], the provisions of the Agreement remain unmodified and the Agreement as amended by this
Change Order # [Insert] is confirmed as being in full force and effect. All defined terms within the Agreement shall have the
same meaning when used herein.

 

Authorized representatives of
the Parties have executed this Change Order # [insert] effective as of the Effective Date written above.

 

	Worldwide
    Clinical Trials, Inc.	 	Neurotrope
    Bioscience, Inc.
	 	 	 
	By:	Sample	 	By:	Sample

 

	Name:	 	 	Name:	 
	 	 	 
	Title:	 	 	Title:	 
	 	 	 
	Date:	 	 	Date:	 

 

    Page 47 of 47

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