Document:

Exhibit

Exhibit 10.3

KANSAS CITY SOUTHERN ANNUAL INCENTIVE PLAN
(As Amended and Restated Effective March 6, 2018)
1.    PURPOSE.  The purpose of the Plan is to provide Eligible Employees of the Employer with annual incentive compensation based on the level of achievement of financial and other performance criteria.  The Plan is intended to focus the interests of these employees on the key measures of the Company's success and to reward these employees for the Company’s achievement of those key measures of the Company's success.  
2.    DEFINITIONS.  As used in the Plan, the following terms shall have the meanings set forth below:
(a)     “Award” shall mean the right to receive a cash payment for a Performance Year payable to a Participant on account of his or her participation in the Plan and achievement of the applicable Performance Goal(s).  
(b)    “Board” shall mean the Board of Directors of the Company.
(c)    “Code” shall mean the Internal Revenue Code of 1986, as amended from time to time, including applicable regulations and rulings thereunder and any successor provisions thereto.
(d)    “Committee” shall mean the Compensation and Organization Committee of the Board (or any successor committee).
(e)    “Company” shall mean Kansas City Southern, and any successor thereto which adopts the Plan.
(f)    “Disability” shall mean a disability as determined under the Employer’s applicable long-term disability program.
(g)    “Eligible Earnings” shall include base earnings and certain pay differentials for time worked in an eligible position during the Performance Year.  
(h)    “Eligible Employee” shall mean an individual who is employed by the Employer who is not represented by a union or other collective bargaining organization.
(i)    “Employer” shall mean the Company and any affiliate of the Company that elects to participate and be an Employer under the Plan with the consent of the Company.
(j)    "Maximum Award" shall mean an Award amount that may be paid if the maximum level of the Performance Goal(s) is achieved in the Performance Year.
(k)    “Participant” shall mean, with respect to any Performance Year, any Eligible Employee who is selected to participate in the Plan in accordance with Section 3 of the Plan.
(l)    “Performance Goal” shall mean the pre-established performance goal(s) established under the Plan for each Performance Year as described in Section 4 of the Plan.
(m)    “Performance Measures” shall mean any criteria on which Performance Goals may be based as determined by the Committee in its discretion, including but not limited to any of the following:      

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(i)    Earnings (either in the aggregate or on a per-share basis); 
(ii)    Net income (before or after taxes); 
(iii)    Operating income;
(iv)    Cash flow;
(v)    Return measures (including return on assets, equity, or sales); 
(vi)    Earnings before or after any, or any combination of, taxes, interest or depreciation and amortization; 
(vii)    Gross revenues; 
(viii)    Share price (including growth measures and stockholder return or attainment by the Company's common stock of a specified value for a specified period of time); 
(ix)    Reductions in expense levels in each case, where applicable, determined either on a Company-wide basis or in respect of any one or more business units; 
(x)    Net economic value; 
(xi)    Market share;
(xii)    Operating profit;
(xiii)    Costs; 
(xiv)    Operating and maintenance cost management and employee productivity; 
(xv)    Stockholder returns (including return on assets, investments, equity, or gross sales); 
(xvi)    Economic value added;
(xvii)    Aggregate product unit and pricing targets;
(xviii)    Strategic business criteria, consisting of one or more objectives based on meeting specified revenue, market share, market penetration, geographic business expansion goals, objectively identified project milestones, production volume levels, cost targets, and goals relating to acquisitions or divestitures;
(xix)    Achievement of business or operational goals such as market share and/or business development;
(xx)    Results of customer satisfaction surveys;
(xxi)    Safety record;
(xxii)    Network and service reliability; 
(xxiii)    Debt ratings, debt leverage and debt service; and/or
(xxiv)    Operating ratio.

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(n)    “Performance Year” shall mean the calendar year of the Company.
(o)    “Plan” shall mean the Kansas City Southern Annual Incentive Plan, as set forth herein, as from time to time amended.
(p)    “Retirement” shall mean an Employee’s separation of employment from the Company with an immediate eligibility to receive a retirement annuity per the provisions of the Railroad Retirement Board.
(q)    “Target Award” shall mean the amount eligible to be paid under an Award if the target Performance Goal(s) is achieved in the Performance Year.
(r)    “Threshold Award” shall mean the amount eligible to be paid under an Award if the threshold Performance Goal(s) is achieved in the Performance Year.    
3.    ELIGIBILITY and PARTICIPATION.  A Participant must be employed by the Employer on the last business day of the Performance Year in order to be eligible to receive payment under an Award, except in the cases of Retirement, death or Disability.
4.    ESTABLISHMENT AND DETERMINATION OF AWARDS.
(a)    Establishment of Performance Goal(s).  After recommendations from senior management of the Company based on consultation with third party sources, the Committee shall establish objective threshold, target, and maximum Performance Goal(s) for each Award after the beginning of each Performance Year, and shall also establish any other bonus payment amounts at other levels of performance. The Performance Goals may be based upon the performance of the Company, the Employer, or any operating unit level, division or function thereof, and may be applied either alone or relative to the performance of other businesses or individuals (including industry or general market indices), based on one or more of the Performance Measures.  All Performance Goals may be expressed as whole dollar amounts, percentages or growth rates.  
With respect to any or all Performance Goal(s) applicable to a Participant, the Company shall also establish, subject to the approval of the Committee, the Threshold Award, Target Award, and Maximum Award payable to the Participant if such Performance Goal(s) is achieved.  Threshold Awards, Target Awards, and Maximum Awards will be expressed as a percentage of a Participant’s Eligible Earnings and correspond to the Participant’s designated Award level unless otherwise determined by the Committee. 
(b)    Payment of Awards.  Unless otherwise determined by the Committee, the payment of any Award shall be subject to achievement of the applicable Performance Goal(s) and the degree to which each of the Performance Goals have been attained.  If a Participant’s Target Award level changes during a Performance Year, the amount of the Participant’s Award will be computed in proportion to his or her Award level that applied to such Participant each day during such Performance Year.    
(c)    Adjustments to Awards.  The Committee may, in its discretion, modify (including by increasing or reducing) the amount of any Award based on such criteria as it shall determine, including, but not limited to, financial results, individual performance, safety performance, business unit and site accomplishments, and other factors tied to the success of the Company or any of its business units.  There is no obligation of uniformity of treatment of Participants under the Plan.

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(d)    Profit Sharing Adjustment.  If, under statutory law, a Participant is entitled to a profit sharing payment from the Employer for a calendar year that coincides with a Performance Year, then the Award amount otherwise payable to the Participant hereunder shall be reduced by an amount equal to such statutory profit sharing amount payable to the Participant.  If applicable, for purposes of calculating such reduction, the statutory profit sharing amount shall be converted to U.S. dollars in accordance with procedures established hereunder. 
5.    PAYMENT OF AWARDS.
(a)    Time of Payment.  An Award shall be paid to a Participant in cash after the Committee has determined that the Performance Goal(s) for the Performance Year have been achieved but in no event later than the 15th day of the third month following the end of such Performance Year.  Notwithstanding the foregoing, an Award with respect to a Performance Year to be paid to a Participant that is not subject to income taxation under the laws of the United States, may be paid later than the 15th day of the third month following the end of such Performance Year, but shall not in any event be paid later than the 30th day of the fourth month following the end of such Performance Year.  Awards payable to other Participants who have had a termination of employment on account of Retirement, death, Disability, or other special circumstance determined appropriate by the Committee during the Performance Year shall be payable in accordance with Section 4(b) of the Plan and at the same time other Participants receive Awards under the Plan.  If the Participant dies prior to receiving payment of an Award, any Award payable under the Plan to such Participant shall be paid to the Participant’s surviving spouse (if married) or estate (if unmarried).
(b)    Withholding.  Awards are subject to withholding for applicable federal, state and local taxes.
6.    PLAN ADMINISTRATION.
(a)    Administration.  The Plan shall be administered by the Committee.  The Committee shall have full discretionary authority to establish the rules and regulations relating to the Plan, to interpret the Plan and those rules and regulations, to determine the Awards and the Performance Measures applicable to each Award, to approve all Awards, to decide the facts in any case arising under the Plan, and to make all other determinations and to take all other actions necessary or appropriate for the proper administration of the Plan.  In making any determinations under or referred to in the Plan, the Committee shall be entitled to rely on opinions, reports or statements of employees of the Company and of counsel, public accountants, and other professional or expert persons.  The Committee’s administration of the Plan, including all such rules and regulations, interpretations, selections, determinations, approvals, decisions, delegations, amendments, terminations and other actions, shall be final and binding on the Company and its stockholders and all employees, including Participants and their beneficiaries.  No member of the Committee shall be liable for any action taken or determination made in good faith with respect to the Plan or any Award.
(b)    Delegation.  Except to the extent prohibited by applicable law or the applicable rules of a stock exchange, the Committee may allocate all or any portion of its responsibilities and powers to any one or more of its members, and may delegate all or any part of its responsibilities and powers for administering the Plan to one or more persons as the Committee deems appropriate, and at any time may revoke any such allocation or delegation. 

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7.    AMENDMENT OR TERMINATION OF PLAN.  The Committee may amend (in whole or in part) or terminate the Plan at any time, effective at such date as the Committee may determine.  The Company also may amend (in whole or in part) or terminate the Plan at any time effective as of such date as the Company may determine, provided, however, any such amendment of the Plan by the Company is subject to the approval of the Committee.
8.    MISCELLANEOUS PROVISIONS.
(a)    Awards Not Transferable.  A Participant’s right and interest under the Plan may not be assigned or transferred.  Any attempted assignment or transfer shall be null and void and shall extinguish, in the Committee’s sole discretion, the Company’s obligation under the Plan to pay Awards with respect to the Participant.
(b)    Effect of Awards on Other Compensation.
1)    Awards shall not be considered eligible pay under other plans, benefit arrangements or fringe benefit arrangements of the Company, unless otherwise provided under the terms of other plans.
2)    To the extent provided in the applicable benefit plan or benefit arrangement of an Employer, amounts payable as Awards will be reduced in accordance with the Participant’s compensation reduction election, if any, in effect under other plans at the time the Award is paid.
(c)    No Employment Rights.  This Plan is not a contract between the Employer and any employee or Participant.  Neither the Plan, nor any action taken hereunder, shall be construed as giving to any Participant the right to be retained in the employ of the Employer.  Nothing in the Plan shall limit or affect in any manner or degree the normal and usual powers of management, exercised by the officers and the Board or any committee of the Board, to change the duties or the character of employment of any employee or to remove an individual from the employment of the Employer at any time, all of which rights and powers are expressly reserved.
(d)    Unfunded Plan.  The Plan shall be unfunded.  No Employer shall be required to establish any special or separate fund, or to make any other segregation of assets, to assure payment of Awards.  Awards shall be paid solely from the general assets of the Participant’s Employer, to the extent the payments are attributable to services for the Employer.  To the extent any person acquires a right to receive payments from an Employer under the Plan, the right is no greater than the right of any other unsecured general creditor.
(e)    Payment in Shares of Company Common Stock.  Notwithstanding any provision in this Plan to the contrary, the Committee may direct that payment of an Award be made in shares of the Company's common stock, in lieu of cash, in accordance with any executive stock ownership guidelines adopted by the Committee.  Any such Award paid in shares of the Company's common stock shall be made pursuant to and in accordance with the Kansas City Southern 2017 Equity Incentive Plan (or any successor plan). 
(f)    Applicable Law.  The Plan shall be governed by the laws of the State of Missouri and applicable federal law.

5Exhibit 10.88

 

Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

 

     

     

    

Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

ATTACHMENT
1

Statement of Work

BCX4430 NDA Enabling CMC and Non-Clinical Toxicology Studies

 

PREAMBLE

 

Independently and not as an agent of the Government, the Contractor
shall furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the
Government as needed to perform the Statement of Work submitted in response to the BARDA Broad Agency Announcement (BAA) CBRN-BAA-10-100-SOL-00013.

 

The Government reserves the right to modify the milestones, progress,
schedule, budget, or deliverables to add or delete deliverables, process, or schedules if the need arises. Because of the nature
of this research and development (R&D) contract and the complexities inherent in this and prior programs, at designated milestones
the Government will evaluate whether work should be redirected, removed, or whether schedule or budget adjustments should be made.

 

OVERALL
OBJECTIVES AND SCOPE

 

The overall objective of this contract is to advance the development
of BCX4430, a novel small molecule nucleoside with broad spectrum antiviral activity being developed for diseases caused by RNA
pathogens. BCX4430, an inhibitor of viral RNA- dependent RNA polymerase (RdRp), is the lead compound in our broad-spectrum antiviral
program to meet the need for a parenteral, direct-acting antiviral medical countermeasure (MCM) having efficacy across multiple
viruses. The scope of work for this contract includes preclinical and manufacturing development activities that fall into the following
areas: manufacturing of clinical trial material, manufacturing process improvements and development, non-clinical toxicology studies;
and all associated regulatory, quality assurance, management, and administrative activities. The R&D effort will contribute
toward an NDA filing for BCX4430. Overall, this Statement of Work (SOW) focuses on:

 

		•	Drug substance (DS) and drug product (DP) manufacturing process development activities that
will be conducted at US based facilities, which will result in the ability to consistently produce high quality, GMP compliant
material and deliver drug supply that could be available for deployment as a medical countermeasure and support future clinical
and non-clinical studies

 

	 	•	Nonclinical development activities to advance the intramuscular (IM) and intravenous (IV) formulation through NDA-enabling toxicology including * * *  and * * * studies in the * * * and * * * 

 

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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

BASE:
MANUFACTURE OF CLINICAL TRIAL MATERIAL

 

Duration: 60 months

 

Drug Substance and Drug Product GMP manufacturing by US suppliers
to support non-clinical and clinical activities. Drug Substance will be produced following an * * * starting with * * * , which
will be used as the starting material to produce GMP BCX4430. Drug Substance will also be produced using an * * * GMP BCX4430.
Previous campaigns of GMP BCX4430 have produced between * * * to * * * per batch. The scope of work under this option will target
up to a 5-fold increase in the GMP BCX4430 batch size.

 

The primary objectives will be to:

 

	 	•	Produce a total off * * * batches of GMP BCX4430 drug substance following the * * * .

 

	 	•	Produce * * * of * * * of non-GMP BCX4430 and * * * of GMP BCX4430 using the * * * 

 

	 	•	Conduct further optimization of the * * * 

 

	 	•	Conduct drug product process improvements that will be focused on validation of analytical methods, stress testing, stability studies, and process design space optimization

 

	 	•	Conduct Drug Product * * * formulation development studies to develop a * * * process that can be scaled to a manufacturing facility

 

	1.1.	Procurement of Starting Materials

 

The contractor shall procure enough starting materials to produce
up to a total of * * * of * * * of the current manufacturing process of BCX4430. The key starting materials to be procured are
* * * and * * * . In addition, the contractor shall procure sufficient starting materials to produce * * * of non-GMP
BCX4430 and * * * of GMP BCX4430 using the * * * .

 

	1.1.1.	Procurement of Starting Materials to produce * * * 

 

The contractor shall procure * * * of * * *
and * * * of * * * for the manufacture of * * * to support an initial campaign (WBS 1.4.1 and 1.4.2)
of manufacturing * * * batches of BCX4430 followed by * * * of BCX4430 (Clinical Trial Material Batch * * *
WBS1.7.1) using the * * * .

 

 

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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	1.1.2.	Procurement of Starting Materials to produce * * * BCX4430 Drug Substance

 

The contractor shall procure sufficient quantities of selected
starting materials to support an initial campaign of manufacturing * * * of BCX4430 using the * * * .

 

	1.2.	Further Process Improvements

 

The contractor shall conduct further process improvements that
may be identified focused on improving the existing plant-scale processes following generally the same * * * .

 

	1.2.1	Conduct Process Improvements

 

The contractor shall conduct the process improvements with existing plant-scale
processes.

 

	1.2.2	Determination that Process is Sufficient to move to Commercial Scale up

 

The contractor shall evaluate the processes developed and provide
sufficient information through a deliverable that will enable BARDA to determine that the * * * process is sufficient
to move to commercial scale-up activities.

 

	1.3.	Manufacture of * * * at * * * 

 

* * * will be utilized as the starting material for
the manufacture of BCX4430 in accordance with GMP guidance.

 

	1.3.1.	Manufacture of the * * *  batch of * * * 

 

The contractor shall target producing between a * * *
batch using * * * .

 

 

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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	1.3.2.	Manufacture of * * * Batches * * * 

 

Based on the performance of the * * * batch of * * *
, additional lab-scale studies and a qualification run will be conducted to improve the * * * process. This process will
then be incrementally scaled-up in the plant.

 

	 	1.3.2.1.	Manufacture of the * * *  batch of * * * 

 

The contractor shall produce approximately * * * per
batch using the * * * .

 

	 	1.3.2.2.	Manufacture of the * * *  batch of * * * 

 

The contractor shall target produce approximately * * *
per batch using the * * * .

 

	1.4.	Manufacturing Campaign of GMP BCX4430

 

The contractor shall produce * * * batches of BCX4430
at * * * in compliance with GMP.

 

	1.4.1.	Manufacturing of the * * *  batch of GMP BCX4430

 

The contractor shall produce and release approximately * * *
of GMP BCX4430 utilizing the * * * process for making BCX4430 starting with the * * * batch (* * *
) of * * * .

 

	1.4.2.	Manufacturing of the * * *  batch of GMP BCX4430

 

The contractor shall produce and release approximately * * *
of GMP BCX4430 utilizing the * * * process for making BCX4430 starting with the recovered portion of the * * *
batch (* * * ) of * * * . NOTE: This quantity is dependent on the amount and quality of * * * isolated
during the recovery of * * * .

 

	1.4.3.	Drug Substance Stability Studies

 

The contractor shall place samples from DS batch and * * *
GMP DS batch of BCX4430 on a * * * stability program at * * * and * * * and a * * * accelerated
stability study at * * * .

 

 

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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

Table 1.    BCX4430 Drug Substance Stability Study Sampling Points

 

	Test	Months
	ID	0	1	3	6	9	12	18	24	48	60
	A	X	X	X	X	X	X	X	X	X	X
	B	X	X	X	X	X	X	X	X	X	X
	C	X	X	X	X	X	X	X	X	X	X
	D	X	X	X	X	X	X	X	X	X	X
	E	X	X	X	X	X	X	X	X	X	X
	F	X	X	 	X	 	X	X	X	X	X
	G	X	X	 	X	 	X	X	X	X	X

 

NOTE: BARDA will only cover stability activities for * * *

 

Table 2.    BCX4430 Drug Substance Stability Tests

 

	Test ID	Test
	A	* * * 
	B	* * * 
	c	* * * 
	D	* * * 
	E	* * * 
	F	* * * 
	G	* * * 

 

	1.5.	Drug Product Development

 

The contractor shall conduct drug product process
improvements that will be focused on validation of analytical methods, stress testing, stability studies, and process design space
optimization for an IM formulation.

 

The contractor shall conduct formulation development activities
and produce a sterile, parenteral formulation containing * * * of the active compound per unit in compliance with GMP
guidance. Initial development efforts will be focused on delivering a * * * that tolerates terminal sterilization and
provides an acceptable stability profile. Additionally, studies to include: * * * will be conducted to evaluate the feasibility
of * * * .

 

	1.5.1.	Stress Conditions Studies

 

The contractor shall conduct a series of experiments
under conditions outlined in ICH guidance to evaluate the stability of the drug product made from available drug substance.

 

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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	1.5.2.	Design Space Studies

 

The contractor shall conduct studies to evaluate and define
the design space of the formulation process.

 

	1.5.3.	Analytical Method Validation

 

The contractor shall conduct analytical methods validation or qualification
as listed in the Table 3 below.

 

Table 3.      BCX4430 Drug Product Methods that will be
Validated or Qualified

 

	Test	Method and Objective
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 
	* * * 	* * * 

 

	1.5.4.	Prepare Process Development Report for DP

 

The contractor shall prepare a process development report summarizing
the experiments and results of the studies conducted to define the process and evaluate the formulation.

 

	1.5.5.	Pre-formulation and Physicochemical Properties Studies

 

The contractor shall conduct studies to determine
the physicochemical properties of the drug substance and identify potential formulations and primary packaging for an IM injection
based on stability and ability to be produced on manufacturing lines.

 

	1.5.6.	Feasibility Runs

 

The contractor shall conduct small-scale, non-GMP
manufacturing runs of potential formulations and formats.

 

	1.5.7.	Extractable/Leachable Study

 

The contractor shall conduct studies to determine drug product stability
in primary packaging and of syringe types that will be used for delivery.

 

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	HHS0100201500007C
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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	1.5.8.	Excipient Compatibility Studies for IV Formulation from IM

 

The contractor shall conduct studies to evaluate the
compatibility of the IM formulation added to various standard IV fluids.

 

	1.6.	Manufacturing of Drug Product to Support Clinical Trials

 

The contractor shall produce * * * of * * *
of drug product suitable for clinical trial use. The drug product will be produced from the * * * GMP BCX4430 DS Batches
(WBS 1.4.1).

 

	1.6.1.	Manufacture of Clinical Trial Material (DP Batch * * * )

 

The contractor shall produce approximately * * * ,
assuming * * * of BCX4430 is delivered from the DS Batch * * * of BCX4430, per GMP for use in clinical trials
which will include active drug batches to support future clinical studies.

 

	1.6.2.	Prepare a Campaign Summary Reports

 

The contractor shall prepare a campaign summary
report of the manufacture and release of the CTM Batch.

 

	1.6.3.	Drug Product Stability Studies - Active

 

The contractor shall place drug product on stability
based on the following conditions:

 

Table 4.      BCX4430 Drug Product Stability Testing Conditions
and sampling

 

	Stability Conditions	Configuration	Test Points
	* * * 	* * * 	* * * 
	* * * 	* * * 	* * * 
	* * * 	* * * 	* * * 

 

 

NOTE: BARDA will only cover stability activities for * * *

 

 

Testing at each interval, unless otherwise specified below,
will include:

 

	 	•	* * * 

	 	•	* * * 

	 	•	* * * 

	 	•	* * * 

 

 

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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	 	•	* * * 

	 	•	* * * 

	 	•	* * * 

	 	•	* * * 

 

	1.6.4.	Comparability Study

 

The contractor shall conduct comparability studies evaluating
drug substance produced by * * * , and the subsequently produced drug product, will be conduct per FDA Guidance. These
studies will evaluate: in-process checks, impurity profiles, release testing results, and stability profiles at standard and accelerated
conditions to ensure the material produced by both manufacturers is substantially comparable.

 

	1.7.	Manufacture of Additional Supply

 

The contractor shall produce approximately * * * of
BCX4430 utilizing the * * * process for BCX4430 from the * * * facility. The contractor shall also produce
* * * of * * * of non-GMP BCX4430 and * * * of GMP BCX4430 using the * * * . The contractor
shall produce approximately * * * of drug product at * * * suitable for clinical trial use.

 

	1.7.1.	Manufacturing of approximately * * * GMP BCX4430

 

The contractor shall produce approximately * * * of
GMP BCX4430 (DS Batch * * * ) from * * * following the * * *

 

	1.7.2.	Prepare a Campaign Summary Report

 

The contractor shall prepare a campaign summary report of the
manufacture and release of DS following completion of * * * manufacture.

 

	1.7.3.	* * * Drug Substance Analytical Method Development and Validation

 

* * * will develop analytical methods suited for the
process followed by validation conducted under protocol. Methods will be validated using standard criteria: * * * . Method
qualification will be conducted prior to validation.

 

	1.7.4.	Manufacturing of approximately * * *  of Non-GMP BCX4430 – * * * 

 

Following the receipt of sufficient quantities of starting materials
and reagents, * * * will qualify the selected process at * * * scale using the * * * DS process.
The Analytical department will support production during the duration of the qualification run. Following completion of manufacturing
the vendor will draft and issue a process qualification report.

 

 

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	HHS0100201500007C
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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	1.7.5.	Manufacturing of approximately * * * of GMP BCX4430 – * * * 

 

Following the receipt of sufficient quantities of starting materials
and reagents, * * * will manufacture * * * of GMP BCX4430 following the * * * . Following completion
of manufacturing, material testing, and release the vendor will draft and issue a campaign Summary Report

 

	1.7.6.	Manufacturing of approximately * * * 

 

The contractor shall produce approximately * * *
of GMP BCX4430 drug product using * * * GMP drug substance (WBS 1.7.1)

 

	1.7.5.	Prepare a Campaign Summary Report

 

The contractor shall prepare a campaign summary report of the
manufacture and release of CTM Batches.

 

	1.7.6.	Stability Studies for DP

 

The contractor shall conduct product stabilities for the DP
manufactured from the batches of GMP BCX4430 drug substance.

 

NOTE: BARDA will only cover stability activities for * * *

 

	1.7.7.	Comparability Studies

 

The contractor shall conduct comparability studies evaluating
drug substance produced by * * * using both processes, and the subsequently produced drug product, will be conduct per
FDA Guidance. These studies will evaluate: in-process checks, impurity profiles, release testing results, and stability profiles
at standard and accelerated conditions to ensure the material produced by both manufacturing processes are substantially comparable.

 

	1.8.	Drug Product * * * Formulation Development

 

* * * has been identified as a potential product presentation
that will provide a stable formulation suitable for IV administration at potentially higher doses than are feasible by * * *
.. A * * * process will be developed that can be scaled to the manufacturing facility.

 

	1.8.1.	Analytical Method Development

 

Confirmation that the * * * is suitable for a * * *
product and qualification of a * * * .

 

	1.8.2.	Pre-formulation Studies

 

Evaluate the current IM formulation and bulking agents to produce
a prototype * * * product.

 

 

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the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	1.8.3.	* * * Cycle Development

 

Evaluate * * * process cycles capable of producing
the final product to specifications utilizing a design of experiments of known critical process parameters. The critical parameters
will be confirmed and ranges established in subsequent small-scale runs.

 

	1.8.4.	Stability Study

 

Evaluate the stability of the product produced during cycle
development. Two fill volumes will be placed on accelerated and real-time studies. * * * will be run for * * *
with * * * and * * * run for * * * .

 

	1.8.5.	Terminal Sterilization

 

Product produced during cycle development will be subjected
to terminal sterilization by gamma irradiation. The irradiated product will be tested for changes in chemical and physical characteristics.

 

	1.8.6.	Pre-manufacturing Studies

 

A material comparability study examining processing and packaging
components will be performed. Additionally, a microbial retention filter validation study will be performed using the * * *
, identified during cycle development.

 

OPTION 1: COMMERCIAL SCALE UP AND NDA REGISTRATION
BATCHES

 

Duration: * * *

 

Go/No Go Criteria to Initiate: WBS 1.2.2 BARDA approval of process
developed Through optimization of manufacturing processes, BARDA will evaluate and determine

 

what process should be sufficient to initiate commercial scale
up activities in this Option. This Option will add value to the project through conducting manufacturing regulatory activities
that will be needed for future product approval with the FDA.

 

Decision Criteria:

 

	·	* * * 

	·	* * * 

 

The objective is to produce DS registration batches from the
qualified process, * * * . This will be determined upon the conclusion of the DS development effort being undertaken
by BioCryst and funded by NIAID that is scheduled to conclude in December 2015. Additionally, during this stage, the DP manufacturing
process would be finalized for the commercial presentation and registration batches produced.

 

 

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the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	2.1.	Procurement

 

The contractor shall procure the * * * and * * *
starting materials needed to produce BCX4430.

 

	2.1.1.	Procurement of * * * 

 

The contractor shall qualify a vendor(s) to produce the * * *
starting material and procure enough material to support the manufacture of * * * batches of BCX4430 drug substance.

 

	2.1.2.	Procurement of * * * 

 

The contractor shall qualify a vendor(s) to produce the * * *
starting material and procure enough material to support the manufacture of * * * batches of BCX4430 drug substance.

 

	2.2.	Drug Substance Process Scale-up

 

The contractor shall conduct process development work targeting
a * * * that can be scaled to plant equipment. This work will include: development of a * * * through lab scale
studies, process hazard evaluation including RC-1 and digital scanning calorimetry, lab scale qualification runs, pilot plant scale-up
technical batches, necessary modifications to analytical methods based on the * * * , and plant-scale registration runs.

 

	2.2.1	Further Process Improvements of Final Route

 

The contractor shall conduct further process improvements that
may be identified focused on improving the * * * to be scaled up. The * * * will be based on * * *
..

 

	2.2.2	Process Hazard Evaluation

 

The contractor shall conduct process hazard evaluation studies needed
for the scale-up of the optimized process into the plant.

 

	2.2.3	Scale-up Technical Run

 

The contractor shall conduct a nonGMP manufacturing run at plant-scale
to ensure the safety and output of the optimized process.

 

	2.2.4	Analytical Method Development and Qualification

 

The contractor shall modify, add to, revalidate, or requalify the analytical
methods.

 

	2.2.5	Prepare Process Development Report

 

The contractor shall prepare a process development report
describing the experiments and results leading to the selection of the optimized manufacturing process

 

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the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	2.3	Manufacture of GMP Drug Substance Registration Batches

 

The contractor shall produce * * * GMP batches of
BCX4430 following the * * * at a scale comparable to the estimated commercial scale.

 

	2.3.1	Manufacture of DS Batch (DS Registration Batch * * * )

 

The contractor shall manufacture a batch of GMP BCX4430 at plant
scale.

 

	2.3.2	Manufacture of DS Batch (DS Registration Batch * * * )

 

The contractor shall manufacture a batch of GMP BCX4430 at plant
scale.

 

	2.3.3	Manufacture of DS Batch (DS Registration Batch * * * )

 

The contractor shall manufacture a batch of GMP BCX4430 at plant
scale.

 

	2.3.4	Prepare Campaign Summary Report

 

The contractor shall prepare a report summarizing the conduct,
observations, and results of the manufacturing of DS Registration Batches * * * .

 

	2.4	Drug Product Registration Batches

 

The contractor shall produce * * *
drug product lots at a qualified CMO that will
be used as the NDA registration batches.

 

	2.4.1	Manufacture of DP Registration (DP Registration Batch * * * )

 

The contractor shall manufacture
a NDA registration batch of GMP BCX4430 drug product at a representative fraction of the estimated commercial scale.

 

	2.4.2	Manufacture of DP Registration (DP Registration Batch * * * )

 

The contractor shall manufacture
a NDA registration batch of GMP BCX4430 drug product at a representative
fraction of the estimated commercial scale.

 

	2.4.3	Manufacture of DP Registration (DP Registration Batch * * * )

 

The contractor shall manufacture a NDA registration batch of
GMP BCX4430 drug product at a representative fraction of the estimated commercial scale.

 

	2.4.4	Prepare campaign summary report

 

The contractor shall prepare a report summarizing the conduct,
observations, and results of the manufacturing of DPR Batches * * * .

 

	2.5	Stability studies for DS and DP

 

The contractor shall conduct drug substance
and drug product stabilities as described in Table 4.

 

NOTE: BARDA will only
cover stability activities for * * *

 

 

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the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	2.6	Comparability study

 

The contractor shall conduct comparability
studies evaluating drug substance produced for clinical trials in
the base period versus the NDA registration batches manufactured via * * * , and
the subsequently produced drug product, will be conduct
per FDA Guidance. These studies will evaluate: in-process
checks, impurity profiles, release testing results, and stability profiles at standard and accelerated conditions to ensure the
material produced by both processes is substantially comparable.

 

OPTION 2: NONCLINICAL NDA-ENABLING TOXICOLOGY

 

Duration: * * *

 

Go/No Go Criteria to Initiate: Availability of GMP BCX4430 * * *
DS batch manufactured under NIAID contract HHS0100201500007

 

Through completion of manufacturing of Drug substance there
will be material to conduct further regulatory activities such as the non-clinical NDA-enabling toxicology studies in this option.
This Option will add value to the project through conducting additional non-clinical activities that will support a potential future
NDA.

 

Decision Criterion:

 

	·	* * * 

	·	* * * 

 

The contractor shall perform nonclinical GLP studies of BCX4430
to characterize * * * .

 

	3.1.	GLP * * * Toxicology

 

The contractor shall for each toxicology study develop the protocol,
select and qualify the vendor, conduct in life and recovery phases and analyze study data resulting in a final study report. Studies
include:

 

	3.1.1.	Conduct GLP * * * toxicology study- * * * 

 

	3.1.2.	Conduct GLP * * * general toxicology study- * * * 

 

	3.2.	* * * toxicology

 

The contractor shall for each * * * study segment
develop the protocol, select and qualify the vendor, conduct in life and recovery phases and analyze study data resulting in a
final study report.

 

Studies include:

 

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	3.2.1.	Conduct * * * assessment in * * * 

 

	3.2.2.	Conduct * * * Dose Range Finding Studies in the * * * 

 

	3.2.3.	Conduct Definitive * * * toxicology in the * * * 

 

	3.2.4.	Conduct * * * toxicology  * * * 

 

	3.3.	Nonclinical ADME

 

The contractor shall procure radiolabeled BCX4430. In addition,
for each ADME study, the contractor shall develop the protocol, select and qualify the vendor, conduct the study and analyze study
data resulting in a final study report. Studies include:

 

	3.3.1.	Conduct Radiolabeled ADME study- * * * 

 

	3.3.2.	Conduct Radiolabeled ADME- * * * 

 

A listing of the proposed studies for the nonclinical NDA-enabling
toxicology studies is provided in Table 5.

 

Table 5.      Nonclinical
NDA-enabling Toxicology Studies

 

	Description	Objectives	Species
	GLP * * * general toxicology	* * * 	* * * 
	GLP * * * general toxicology	* * * 	* * * 
	* * * assessment	* * * 	* * * 

 

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	Description	Objectives	Species
	* * * Dose Range Finding	* * * 	* * * 
	* * * Dose Range Finding	* * * 	* * * 
	Definitive * * * toxicology	* * * 	* * * 
	Definitive * * * toxicology	* * * 	* * * 
	* * * toxicology	* * * 	* * * 
	Radiolabeled ADME	Determine the absorption, distribution, metabolism and excretion of the test article following IM dosing	* * * 
	Radiolabeled ADME	Determine the absorption, metabolism and excretion of the test article following IM dosing	* * * 

 

 

OPTION 3: IN VITRO EXPERIMENTS- IV

 

Duration: * * *

 

Go/No Go to Initiate: Selection of a preliminary IV formulation
(LRI) based on initial studies

 

Through completion of earlier studies, an appropriate IV formulation
to continue with toxicology studies of the IV formulation under this Option will be determined. This Option will add value to determine
if there is any identified toxicology in
in vitro assays before moving
to animal studies in Option 4.

 

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the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

Decision Criterion:

 

	 	•	* * * 

 

	4.1.	* * * - IV

 

The contractor shall develop the
protocol, select and qualify the vendor, conduct the experiments
and analyze the data resulting in a study report.

 

	4.2.	Conduct * * * Test -IV

 

The contractor shall develop the protocol, select and qualify
the vendor, conduct the experiment and analyze the data resulting in a study report.

 

A listing of the proposed experiments
for the in vitro experiments to be conducted in advance of the nonclinical NDA-enabling toxicology studies for the
IV formulation is provided
in Table 6.

 

Table 6.Invitro Experiments – IV

 

	Description	Objective(s)	Species
	* * * 	* * * 	* * * 
	* * * 	* * * 	* * * 

 

  

	4.3	Study Report on all in vitro assays

 

The contractor shall submit a summarized
study report with data and conclusions from all in vitro
experiments conducted in Table 6 to determine whether there is any toxicology before advancing into non-clinical NDA enabling toxicology
studies (Option 5).

 

OPTION 4:
NONCLINICAL NDA-ENABLING TOXICOLOGY

 

Duration: * * *

 

Go/No Go Criteria to Initiate: WBS 4.3 Study
Report on all in vitro assays

 

Through completion of the IV in
vitro toxicology studies with the IV
formulation conducted in Option 3 and summarized in WBS
4.3, it will be determined if the IV formulation is safe
to move into non-clinical toxicology animal studies in this Option. This Option will add value to
the project through conducting
additional non-clinical activities that will support a potential future NDA.

 

 

 

 

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Decision Criterion:

 

	 	•	* * * 

 

	 	•	* * * 

 

	5.1.	GLP * * * Toxicology

 

The contractor shall for each toxicology study develop the protocol,
select and qualify the vendor, conduct in life and recovery phases and analyze study data resulting in a final study report. Studies
include:

 

	5.1.1.	Conduct GLP * * * general toxicology study- * * * 

 

	5.1.2.	Conduct GLP * * * toxicology study - * * * 

 

	5.2.	* * * toxicology

 

The contractor shall for each * * *
study segment develop the protocol, select and qualify the vendor, conduct in life and recovery phases
and analyze study data resulting in a final study report. Studies
include:

 

	5.2.1.	Conduct * * * assessment in * * * 

 

	5.2.2.	Conduct * * * Dose Range Finding Studies in the * * * 

 

	5.2.3.	Conduct Definitive * * * toxicology in the * * * 

 

	5.2.4.	Conduct * * * toxicology * * * 

 

A listing of the proposed studies
for the nonclinical NDA-enabling toxicology studies for the IV formulation is provided in Table
8.

 

Table 8:     Nonclinical
NDA-enabling Toxicology Studies

 

	Description	Objectives	Species
	GLP * * * general toxicology	* * * 	* * * 

 

 

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	Description	Objectives	Species
	GLP * * * general toxicology	* * * 	* * * 
	* * * assessment	* * * 	* * * 
	* * * Dose Range Finding	* * * 	* * * 
	* * * Dose Range Finding	* * * 	* * * 
	Definitive * * * toxicology	* * * 	* * * 
	Definitive * * * toxicology	* * * 	* * * 
	* * * toxicology	* * * 	* * * 

 

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6    PROGRAM MANAGEMENT

 

The contractor shall provide all expertise needed
for the implementation of the activities to be performed under this contract, including: research, manufacturing, regulatory, clinical,
statistical analyses, management and administrative activities.

 

	6.1.	Technical and Project Management Support

 

The contractor shall appoint a Principal Investigator
(PI) who will be responsible for all aspects of project performance and communication with BARDA.

 

The contractor shall provide project management
that will ensure day-to-day monitoring and tracking of progress and timelines, the coordination of project activities and costs
incurred.

 

The contractor shall provide all managerial and
administrative functions necessary for overall planning, monitoring, and implementing activities for the completion of the strategic
product development plan.

 

The contractor shall provide
for all necessary legal affairs required to ensure the timely acquisition of all proprietary rights, including intellectual property
rights and all materials needed to perform the project, as well as reporting to the Government all inventions made in the performance
of the project.

 

	6.2.	Subcontractor Management

 

The contractor shall provide for tracking, coordination and
oversight of subcontractor efforts and manage communications with subcontractors.

 

	6.3.	Risk Management

 

The contractor shall identify project risks, develop
risk management strategies and implement mitigation actions.

 

	6.4.	Earned Value Management (EVM)

 

The contractor shall provide EVM information.

 

	6.5.	Project Communications

 

The contractor shall provide for project communications
including communications with BARDA and external experts.

 

The contractor shall provide planning and steps required for the conduct
of contract review meetings.

 

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7    REGULATORY

 

The contractor shall ensure adherence to FDA regulations
and guidance, including requirements for the conduct of animal studies and assays under GLP, the manufacturing of the therapeutic
product under GMP, and the conduct of clinical trials under GCP standards.

 

	7.1.	Regulatory Authority Interactions

 

The contractor shall prepare and submit documentation
and correspondence to regulatory authorities as required. The contractor shall request and conduct meetings with regulatory authorities
to ensure the development program is conducted in accordance with regulatory guidelines and expectations.

 

	7.2.	Quality Assurance

 

The contractor shall maintain quality assurance
documentation. The contractor shall arrange for audits of subcontractor facilities to ensure all planned procedures comply with
the FDA regulations and guidance that are required to meet GLP, GMP and GCP standards. In addition, the contractor shall ensure
that all contractor and/or subcontractor records and staff are available for site visits or audits.

 

	7.3.	Expert Collaborations

 

The contractor shall collaborate with experts in the
field in the design of experiments and studies that support the advancement of the development program.

 

 

 

 

 

 

 

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MILESTONE
AND DELIVERABLES CHART

BioCryst
Pharmaceuticals Contract HHS0100201500007C

 

	WBS	Milestone	Deliverable	Success Criteria	Timing	Go/No-go 

for initiation
	CLIN 0001 – MANUFACTURE OF CLINICAL TRIAL MATERIAL
	1.2.1	Process Improvements Report	Report on Process Development	Process Developed	* * * 	 
	1.2.2	Determination of sufficient Process for Commercial Scale up	Evaluation Report	BARDA approval of developed process	* * * 	N/A
	1.3.1	Manufacture of * * * (Batch * * * )	* * * 	Acceptable quality and yield	* * * 	N/A
	1.3.2	Manufacture of * * * (Batch * * * )	* * * 	Acceptable quality and yield	* * * 	N/A
	1.3.3	Manufacture of * * * (Batch * * * )	* * * 	Acceptable quality and yield	* * * 	N/A
	1.4.1	Manufacture of GMP BCX4430 (DS Batch * * * )	BCX4430 DS CofA	Acceptable quality and yield	* * * 	N/A
	1.4.2	Manufacture of GMP BCX4430 (DS Batch * * * )	BCX4430 DS CofA	Acceptable quality and yield	* * * 	N/A
	 	 	 	 	 	 
	1.4.3	Drug Substance Stability Study	Report on stability activities	Stability Data	* * * 	N/A
	1.5	Drug Product Development	DP Process Development Report (WBS 1.5.4)	Completion of studies	* * * 	N/A
	 	 	Pre-formulation and Physicochemical Report (WBS 1.5.5)	 	 	 
	 	 	Extractable/Leachable Report (WBS 1.5.7)	 	 	 
	1.5.8	Excipient Compatibility Report for IV Formulation	Compatibility Report	IV Formulation Completed	* * * 	N/A
	1.6.1	Manufacture GMP DP (DP Batch * * * )	BCX4430 DP, CofA	Acceptable quality and yield	* * * 	Accepted GMP DS
	1.6.2	Prepare a Campaign	Campaign Summary Report (DP Batch * * * )	Completion of DP Campaigns	* * * 	N/A

 

 

 

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	WBS	Milestone	Deliverable	Success Criteria	Timing	
        Go/No-go
        for

        initiation

	 	Summary Report	 	 	 	 
	1.6.3	Drug Product Stability Study - Active	Report of Stability Activities	Stability Data	* * * 	N/A
	 	 	 	 	 	 
	1.6.4	Comparability Study	Comparability Protocol and Report	Completion of DS and DP Campaigns	* * * 	N/A
	1.7.1	
        Manufacture
        of GMP BCX4430

        (DS Batch * * *
        )
	BCX4430 DS, CofA	Acceptable DS process	* * * 	N/A
	 	 	 	 	 	 
	1.7.2	
        Prepare a

        Campaign
        Summary Report
	Campaign Summary Report (DS Batch * * * )	Completion of DS Campaign	* * * 	N/A
	1.7.3	
        * * * DS Analytical
        Method Development

        and Validation
	Validation Report	Suitable assay method	* * * 	N/A
	1.7.4	
        * * * DS – Manufacture

        * * * of Non-
        GMP BCX4430
	BCX4430 DS	Acceptable quality and yield	* * * 	N/A
	1.7.5	
        * * * DS – Manufacture

        * * * of GMP
        BCX4430
	BCX4430 DS, CofA	Acceptable quality and yield	* * * 	N/A
	1.7.6	Manufacture GMP DP (* * * )	BCX4430 DP CofA	Acceptable Quality and yield	* * * 	Accepted GMP DS
	1.7.7	
        Prepare a Campaign

        Summary Report
	Campaign Summary Report (CTM Batch * * * )	Completion of DS Campaign	* * * 	N/A
	1.7.8	Drug Product Stability study	Report on Stability Activities	Stability Data	* * * 	Manufacture of 1.7.1 & 1.7.2 DS and 1.7.4 DP
	1.7.9	Comparability Study	Comparability Protocol and Report	Comparable DS and DP profiles	* * * 	N/A
	1.8	Drug Product * * * formulation Development	* * * Process that can be scaled to a manufacturing facility	Suitable * * * /Finalized process	* * * 	N/A
	
        CLIN 0002 – COMMERCIAL
        SCALE UP AND NDA REGISTRATION BATCHES

        Go/No Go Criteria to Initiate:
        WBS 1.2.2 BARDA approval of process developed

	2.2	Drug Substance Process Scale-	Process Development Report (WBS 2.2.4)	Selection of the optimized	* * * 	* * * 

 

 

 

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	WBS	Milestone	Deliverable	Success Criteria	Timing	
        Go/No-go
        for

        initiation

	 	Up	 	manufacturing process	 	* * * 
	2.3.1	
        Manufacture
        BCX4430 (DS

        Registration Batch * * *
        )
	BCX4430 Registration DS, CofA	Acceptable quality and yield	* * * 	* * * 
	2.3.2	
        Manufacture
        BCX4430 (DS

        Registration Batch * * *
        )
	BCX4430 Registration DS, CofA	Acceptable quality and yield	* * * 	* * * 
	2.3.3	
        Manufacture
        BCX4430 (DS

        Registration Batch * * *
        )
	BCX4430 Registration DS, CofA	Acceptable quality and yield	* * * 	* * * 
	2.3.4	
        Prepare a Campaign

        Summary Report
	Campaign Summary Report (DS Batches * * * )	Completion of DS Campaign	* * * 	N/A
	2.4.1	
        Manufacture
        BCX4430 DP

        (DP Registration Batch * * *
        )
	BCX4430 DP CofA	Acceptable quality and yield	* * * 	Accepted GMP DS
	2.4.2	
        Manufacture
        BCX4430 DP

        (DP Registration Batch * * *
        )
	BCX4430 DP CofA	Acceptable quality and yield	* * * 	Accepted GMP DS
	2.4.3	
        Manufacture
        BCX4430 DP

        (DP Registration Batch * * *
        )
	BCX4430 DP CofA	Acceptable quality and yield	* * * 	Accepted GMP DS
	2.4.4	Prepare a Campaign Summary Report	Campaign Summary Report (CTM Registration Batches * * * )	Completion of DS Campaign	* * * 	N/A
	2.5	
        Drug
        Substance and Drug

        Product Stability Study
	Report on stability activities	Stability Data	* * * 	N/A
	2.6	Comparability Study	Comparability Protocol and Report	Comparable DS and DP profiles	* * * 	Accepted GMP DS
	
        CLIN 003 – NONCLINICAL NDA-ENABLING
        TOXICOLOGY

        Go/No-go Criteria to
        Initiate: Availability of * * * of GMP batch of DS manufactured under NIAID contract HHSO100201500007C

	3.1.1	Complete GLP * * * Tox Study - * * * 	Study Report	Establish NOAEL	* * * 	Drug Substance confirming to release criteria
	3.1.2	Complete GLP * * * Tox Study - * * * 	Study Report	Establish NOAEL	* * * 	Drug Substance confirming to release

 

 

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	WBS	Milestone	Deliverable	Success Criteria	Timing	
        Go/No-go
        for

        initiation

	 	 	 	 	 	criteria
	3.2.1	
        Conduct
        * * * Assessment in

        * * *
	Study Report	No significant findings	* * * 	N/A
	3.2.2	Conduct * * * Dose Range Finding Studies in * * * 	Study Report	No significant findings	* * * 	N/A
	3.2.3	Conduct Definitive * * * Development Studies in * * * 	Study Report	No significant findings	* * * 	N/A
	3.2.4	
        Conduct
        * * * Toxicology

        * * *
	Study Report	No significant findings	* * * 	N/A
	3.3.1	Conduct Radiolabeled ADME study - * * * 	Study Report	Characterize drug disposition	* * * 	Acceptable Radiolabel Material
	3.3.2	Conduct Radiolabeled ADME study – * * * 	Study Report	Characterize drug disposition	* * * 	Acceptable Radiolabel Material

 

CLIN 0004 – IN VITRO EXPERIMENTS –
IV 

Go/No Go to Initiate: Selection of an appropriate
preliminary IV formulation

	4.1	
        Conduct * * *
        Test

        - IV
	Study Report	No effect on * * * ex-vivo	* * * 	IV formulation WBS 1.5.8
	4.2	
        Conduct
        * * *

        Test IV
	Study Report	No effect on mitotic apparatus	* * * 	N/A
	4.3	In Vitro IV experiments	Study report on all In Vitro assays with recommendation to proceed to CLIN005	No toxicology in vitro	* * * 	 

 

CLIN 0005 NONCLINICAL NDA-ENABLING TOXICOLOGY

Go/No-Go to Initiate:
WBS 4.3 Completion of * * * IV toxicology studies

	5.1.1	Complete GLP * * * Tox	Study Report	Establish NOAEL	* * * 	Drug Substance

 

 

    	Page 4 of 5
	HHSO100201500007C
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Pursuant to
17 CFR 20.24b-2, confidential information has been omitted in places marked "***" and has been filed separately with
the Securities and Exchange Commission pursuant to a Confidential Treatment Request with the Commission.

 

 

	WBS	Milestone	Deliverable	Success Criteria	Timing	
        Go/No-go
        for

        initiation

	 	Study - * * * 	 	 	 	Confirming to release criteria
	5.1.2	Complete GLP * * * Tox Study - * * * 	Study Report	Establish NOAEL	* * * 	Drug Substance Confirming to release criteria
	5.2.1	Conduct * * * Assessment in * * * 	Study Report	No significant findings	* * * 	N/A
	5.2.2	Conduct * * * Dose Range Finding Studies in * * * 	Study Report	No significant findings	* * * 	N/A
	5.2.3	Conduct Definitive * * *  Studies in * * * 	Study Report	No significant findings	* * * 	N/A
	5.2.4	Conduct * * * Toxicology * * * 	Study Report	No significant findings	* * * 	N/A

 

*Timing
will depend on approval of additional CLIN1 funds/IPR approval to

 

 

 

 

 

 

 

 

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