EXHIBIT 10.2


 


 









     


     


    

 









     


     


    

 


 



    	 



     

    




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
Application with the Commission.


 


 


 










ATTACHMENT 1


Statement of Work


HHSO100201500007C


BCX4430 NDA Enabling CMC and Non-Clinical Toxicology Studies


August 19, 2015


 


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 proposed activities take into
account the Ebola virus disease (EVD) outbreak in West Africa. 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, cGMP compliant material
and deliver drug supply that could be available for deployment as a medical countermeasure during the Ebola crisis 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 ***







     


     
 
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 Application with the Commission.
 


    


		1	BASE:
                                         Manufacture of Clinical Trial Material



Duration: 18 months


Drug Substance and Drug Product cGMP 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 GMP starting
material to produce BCX4430.


The primary objectives will be to


		·	Produce *** batches of BCX4430 drug substance following ***.



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



1.1.       
Procurement of Starting Materials


The contractor shall procure the starting materials to produce *** of the current manufacturing
process of BCX4430. The key starting materials to be procured are *** and ***.


1.1.1.   Procurement of Starting Materials
to produce two 35 kg batches of BCX1777


The contractor shall procure *** and *** for the manufacture of *** of *** to support
a *** campaign (WBS 1.4.1 and 1.4.2) and a *** batch of BCX4430 (Clinical Trial Material Batch *** WBS1.7.1)


1.2.       
Further Process Improvements of ***


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 processes are sufficient to move to commercial scale –up
activities.


1.3.       
Manufacture of *** at ***


The contractor shall produce *** of *** will be utilized as the starting material for
the manufacture of BCX4430 in accordance with cGMP guidance.


1.3.1.   Manufacture of *** of ***
(Batch ***)


The contractor shall produce *** of *** using the existing process at ***.


1.3.2.   Manufacture of *** of ***
(Batch ***)


The contractor shall produce *** of *** using the existing process at ***.


1.4.       
Manufacturing Campaign of BCX4430


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


1.4.1.   Manufacturing of *** of cGMP
BCX4430 (DS Batch ***)


The contractor shall produce and release *** of cGMP BCX4430 ***.



     


     
 
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 Application with the Commission.
 


    




1.4.2.   Manufacturing of *** of cGMP
BCX4430 (DS Batch ***)


The contractor shall produce and release *** of cGMP BCX4430 ***.


1.4.3.   Prepare a Campaign Summary
Report


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


1.4.4.   Drug Substance Stability Studies


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


Table 1. BCX4430 Drug Substance Stability
Study Sampling Points


	
        Test

        ID
	Months
	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.


The contractor shall conduct formulation development activities and produce a sterile,
parenteral formulation containing *** of the active compound per unit in compliance with cGMP guidance. Initial development efforts
will be focused on delivering *** that tolerates terminal sterilization and provides an acceptable stability profile to support
a *** shelf life. 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.


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 below.



     


     
 
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 Application with the Commission.
 


    

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, nonGMP 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.


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 *** batches of approximately *** of drug product suitable
for clinical trial use. The drug product will produced from the *** cGMP DS Batches *** (WBS 1.4.1 and 1.4.2)


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


The contractor shall produce approximately *** per cGMP for use in clinical trials which
will include active drug and placebo batches to support the future clinical safety study.


1.6.2.   Manufacture of Clinical Trial
Material (CTM Batch ***)


The contractor shall produce approximately *** per cGMP for use in clinical trials which
will include active drug and placebo batches to support the future clinical safety study.






     


     
 
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 Application with the Commission.
 


    



1.6.3.   Prepare a Campaign Summary
Reports


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


1.6.4.   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:


***


1.6.5.   Drug Product Stability Studies
- Placebo


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


Table 5. BCX4430 Drug Product Stability
Testing Conditions and Sampling


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


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


***


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


1.6.6.   Comparability Study


The contractor shall conduct comparability studies evaluating drug substance produced
by *** and ***, 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


That contractor shall produce *** of BCX4430 based on *** facility and subsequently produce
*** of drug product at *** suitable for clinical trial use.


1.7.1.   Manufacturing of *** cGMP
BCX4430 (DS Batch ***)


The contractor shall produce *** of cGMP BCX4430 from ***.






     


     
 
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 Application with the Commission.
 


    

1.7.2.   Prepare a Campaign Summary
Report


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


1.7.3.   Manufacturing of approximately
*** (CTM Batch ***)


The contractor shall produce approximately *** of cGMP BCX4430 drug product using drug
substance from the *** cGMP BCX4430 (DS Batch ***, WBS 1.7.1).


1.7.4.   Prepare a Campaign Summary
Report


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


1.7.5.   Stability Studies for DS and
DP


The contractor shall conduct drug substance and drug product stabilities for the DS and
DP manufactured in from the *** of cGMP BCX4430 drug substance based on *** (WBS 1.6).


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


1.7.6.   Comparability Studies


The contractor shall conduct comparability studies evaluating drug substance produced
by *** and both process at ***, 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 and both *** process are substantially comparable.


 


2
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.






2.1.       
Procurement


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


2.1.1.   Procurement of ***


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



     


     
 
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 Application with the Commission.
 


    

2.1.2.   Procurement of ***


The contractor shall qualify a vendor(s) to produce the *** 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 either ***.


		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


2.3        
Manufacture of cGMP Drug Substance Registration Batches


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


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



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


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


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


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


The contractor shall manufacture a batch of cGMP 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 Batches ***.



     


     
 
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 Application with the Commission.
 


    

2.4        
Drug Product Registration Batches


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


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


The contractor shall manufacture a NDA registration batch of cGMP BCX4430 drug product
at a scale at least *** the estimated commercial scale.


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


The contractor shall manufacture a NDA registration batch of cGMP BCX4430 drug product
at a scale at least *** the estimated commercial scale.


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


The contractor shall manufacture a NDA registration batch of cGMP BCX4430 drug product
at a scale at least *** 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 2 and Table 3 .


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





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 *** in Option 1, 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.






     


     
 
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 Application with the Commission.
 


    



 


3
Option 2: Nonclinical NDA-enabling Toxicology




Duration: ***


Go/No Go Criteria to Initiate: Availability of cGMP BCX4430 *** DS batch manufactured
under NIAID contract HHSO100201500007C


Through completion of manufacturing of Drug substance there will be material to conduct further
regulatory activities such as the IM 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:






     


     
 
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 Application with the Commission.
 


    

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:


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.


 





Table 6 Nonclinical NDA-enabling
Toxicology Studies


	Study #	Description	Objective(s)	Species (N)
	 	GLP *** general toxicology	***	***
	 	GLP *** general toxicology	***	***
	 	*** assessment	***	***
	 	*** 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	***






     


     
 
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 Application with the Commission.
 


    



 


 


4
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, it will be determined what is an appropriate IV formulation
to continue with toxicology studies of the IV formulation under this Option. 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.


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
7 .


Table 7 In vitro Experiments - IV


	Study #	Description	Objective(s)	Species (N)
	 	***	***	***
	 	***	***	***


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 7 to determine whether there is any toxicology before advancing into non-clinical NDA
enabling toxicology studies (Option 5).






     


     
 
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 Application with the Commission.
 


    



 


 


5
Option 4: Nonclinical NDA-enabling Toxicology - IV




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.


Decision Criterion:


		·	***



		·	***





		5.1.	GLP *** Toxicology – IV



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 *** IV general toxicology study - ***


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


5.2.       
*** toxicology - IV


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.






     


     
 
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 Application with the Commission.
 


    




 


 


Table 8. Nonclinical NDA-enabling
Toxicology Studies for an IV Formulation


	Study #	Description	Objective(s)	Species (N)
	 	GLP *** IV general toxicology	***	***
	 	GLP *** IV general toxicology	***	***
	 	*** assessment	***	***
	 	*** Dose Range Finding	
        ***

        
	***
	 	*** Dose Range Finding	
        ***

        
	***
	 	Definitive *** toxicology	***	***
	 	Definitive *** toxicology	***	***
	 	*** toxicology	***	***


 


 



     


     
 
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 Application with the Commission.
 


    



 


 


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 the 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.






     


     
 
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 Application with the Commission.
 


    



 


 


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 cGMP, 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, cGMP 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.


 



     


     
 
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 Application with the Commission.
 


    






ATTACHMENT 2


MILESTONE AND DELIVERABLES CHART


August 20, 2015


HHSO100201500007C


	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 *** (Batch ***)	***	Acceptable quality and yield	***	N/A
	1.3.2	Manufacture *** (Batch ***)	***	Acceptable quality and yield	***	N/A
	1.4.1	Manufacture cGMP BCX4430 (*** campaign DS Batch ***)	
        BCX4430 DS

         

        CofA,

         
	Acceptable quality and yield	***	N/A
	1.4.2	Manufacture cGMP BCX4430 (*** campaign DS Batch ***)	
        BCX4430 DS

         

        CofA,

         
	Acceptable quality and yield	***	N/A
	1.4.3	Prepare a Campaign Summary Reports	Campaign Reports (DS Batches ***)	Completion of DS Campaigns	***	N/A
	1.4.4	Drug substance stability study 	Initial Report on stability activities 	Stability data	***	 
	1.5	Drug Product Development	
        DP Process Development Report (WBS 1.5.4)

         

        Pre-formulation and Physicochemical Report (WBS1.5.5)

         

        Extractable/Leachable Report (WBS 1.5.7)

         

         
	Completion of Studies	***	N/A
	1.5.8	Excipient Compatibility Report for IV Formulation	Compatibility Report 	IV formulation completed	***	 
	1.6.1	Manufacture cGMP DP (CTM Batch ***)	
        BCX4430 DP

         

        CofA,
	Acceptable quality and yield	***	Accepted GMP DS
	




     


     
 
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 Application with the Commission.
 


    


	1.6.2	Manufacture cGMP DP (CTM Batch ***)	
        BCX4430 DP

         

        CofA,
	Acceptable quality and yield	***	Accepted GMP DS
	1.6.3	Prepare a Campaign Summary Reports	Campaign Reports (CTM Batches ***)	Completion of DP Campaigns	***	N/A
	1.6.4	Drug Product stability study - Active	Initial Report on stability activities 	Stability Data	***	 
	1.6.5	Drug Product stability study - Placebo	Initial Report on stability activities 	Stability Data	***	 
	1.6.6 	Comparability Study	Comparability Protocol and Report	Completion of DS and DP Campaigns	***	 
	1.7.1 	Manufacture cGMP BCX4340 (*** campaign DS Batch ***)	
        BCX4430 DS

         

        CofA
	Acceptable DS process 	***	N/A
	1.7.2	Prepare a Campaign Summary Report	Campaign Reports (DS Batch***)	Completion of DS Campaign	***	N/A
	1.7.3	Manufacture cGMP DP (CTM Batch ***)	
        BCX4430 DP

         

        CofA,
	Acceptable quality and yield	***	Accepted GMP DS
	1.7.4	Prepare a Campaign Summary Report	Campaign Report (CTM Batches ***)	Completion of DS Campaigns	***	N/A
	1.7.5	Drug Substance and Drug Product stability study	Initial report on stability activities 	Stability Data	***	Manufacture of 1.7.1 drug substance and 1.7.2 drug product
	1.7.6	Comparability Study	Comparability Protocol and Report	Comparable DS and DP profiles	***	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-up 	Process Development Report (WBS 2.2.4)	Selection of the optimized manufacturing process	***	*** process
	
        2.3.1

         
	Manufacture BCX4340 DS (DS Registration Batch ***)	
        BCX4430 Registration

        DS

         

        CofA
	Acceptable quality and yield	***	*** process 
	
        2.3.2

         
	Manufacture BCX4340 DS (DS Registration Batch ***)	
        BCX4430 Registration DS

         

        CofA,
	Acceptable quality and yield	***	*** process 
	
        2.3.3

         
	Manufacture BCX4340 DS (DS Registration Batch ***)	
        BCX4430 Registration DS

         

        CofA,
	Acceptable quality and yield	***	*** process 
	




     


     
 
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 Application with the Commission.
 


    


	2.3.4	Prepare a Campaign Summary Report	Campaign Reports (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 Report (CTM Registration Batches ***)	Completion of DS Campaigns	***	N/A
	2.5	Drug substance and Drug Product stability study	Report on stability activities 	Stability Data	***	 
	2.6	Comparability Study	Comparability Protocol and Report	Comparable DS and DP profiles	***	Accepted GMP DS
	
        CLIN 0003 – NONCLINICAL NDA-ENABLING TOXICOLOGY 

        Go/No Go Criteria to Initiate: /availability
        of *** cGMP batch of DS manufactured under NIAID contract HHSO100201500007C

	3.1.1	Complete GLP ***Tox Study - ***	Study Report	Established NOAEL	***	Drug Substance confirming to release criteria
	3.1.2	Complete GLP *** Tox Study - ***	Study Report	Established NOAEL	***	Drug Substance confirming to release criteria
	3.2.1	Conduct *** assessment in ***	Study Report	No significant findings	***	N/A
	3.2.2	Conduct *** Dose Range Finding Studies in the ***	Study Report	No significant findings	***	N/A
	3.2.3	Conduct Definitive *** toxicology in the ***	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 Report	Characterize drug disposition	***	Acceptable Radiolabel Material 
	




     


     
 
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 Application with the Commission.
 


    


	
        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 ***	***	IV formulation WBS 1.5.8
	4.2.	Conduct *** – 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 CLIN0005	No toxicology in vitro	***	 
	
        CLIN 0005 – NONCLINICAL NDA-ENABLING TOXICOLOGY – IV

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

	5.1.1	Complete GLP *** IV Tox Study - ***	Study Report	Established NOAEL	***	Drug Substance confirming to release criteria
	5.1.2	Complete GLP *** IV Tox Study - ***	Study Report	Established 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 the ***	Study Report	No significant findings	***	N/A
	5.2.3	Conduct Definitive *** toxicology in the ***	Study Report	No significant findings	***	N/A
	5.2.4	Conduct *** toxicology ***	Study Report	No significant findings	***	N/A


 






     


     
 
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 Application with the Commission.
 


    







 


 


ATTACHMENT 3


BCX4430 MANUFACTURING SUMMARY


August 20, 2015


 


	Starting Material	DS Campaign	CMO	DS Process Desc	DS Timing	DP Campaign	DP Timing	Use	Funding
	***	***	***	***	***	***	***	***	***
	***	***	***	***	***	***
	***	***	***	***	***	***	***	***
	***	***	***	***	***	***	***
	***	***	***	***	***	***	***	***
	***	***	***	***	***	***	***	***
	***	***	***	***	***	***	***
	***	***	***	***	***	***	***	***
	***	***	***	***	***	***	***	***
	***	***	***	***	***	***	***	***	***
	***	***	***	***	***	***	***
	***	***	***	***	***	***	***
	***


 


 



     


     
 
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 Application with the Commission.
 


    







 


 


Attachment 4


HHSO100201500007C


August 20, 2015


 


***


 


 


 


 


 


 





All activities covered under this BioCryst contract will provide merit
and value to the Government by ensuring that funding supported under the Base period results in progress towards several activities
to ensure moving the BioCryst BCX4430 compound through the development pipeline for future FDA approval. This activities include
manufacturing clinical trial material to be used in clinical trials as an urgent need to the Ebola epidemic in west Africa (Base),
commercial scale up and manufacturing of registration batches, a regulatory approval requirement (Option 1), non-clinical toxicology
studies to support NDA regulatory requirements (Option 2) and non-clinical toxicology studies of the IV formulation first in vitro
(Option 3) and then in animals (Option 4) to support NDA regulatory requirements. BioCryst’s ability to complete three critical
GO/NO GO contract milestones in the Base period will determine, whether to exercise any follow-on option phases to continue supporting
development of the compound.


 


There are 4 decision points which will trigger advancement to Options. 


 


		1.	Trigger 1 (for start of Option 1):  Further optimization processes
for manufacturing will be developed under the WBS 1.2  Once these activities are sufficient to warrant a scale up manufacturing
process, as will be evaluated in a delivered report, process development (milestone WBS1.2, July 2015), Option 1 can begin. 
In Option 1, the process developed in WBS 1.2 and other processes being developed to manufacture the BCX4430 compound will be evaluated,
such that BioCryst can select a process of most value to the Government to generate *** drug
substance registration batches that will then be used to make *** drug product registration
batches at a scale at least *** the estimated commercial scale which is a regulatory requirement
for qualifying a GMP process for manufacturing.



 



     


     
 
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 Application with the Commission.
 


    




		2.	Trigger 2 (for start of Option 3): In order to conduct toxicology experiments in animals, the IV
formulation of BCX4430 will first need to be assessed in vitro through *** as well as *** (Option 3) before moving
into animals. Initially a go/no go milestone was established to evaluate excipient compatibility of the IV formulation before initiating
these studies. However, since BioCryst has determined that the BCX4430 drug substance to be used in these studies will be available
and released *** as well as having identified a preliminary IV solution (LRI) based on initial results, it was determined that
there was sufficient data to support the initiation of these in vitro toxicology studies of this formulation - Option 3
(in Vitro experiments- IV) before moving in to animal toxicology studies (Option 4).



 


		3.	Trigger 3 (for start of Option 2):  In order to conduct further regulatory activities to
support NDA activities, toxicology experiments will need to be conducted in animals as well as radiolabeled absorption, metabolism
and excretion studies.  The original go/no go criteria was to generate enough drug substance material WBS 1.4.1 that conformed
to release criteria to use in these studies. However additional batches of BCX4430 have been manufactured that will start to be
available *** and therefore should provide enough material to conduct these non-clinical animal toxicology studies in Option 2,
a NDA regulatory requirement.



 


		4.	Trigger 4 (for start of Option 4):  In order to proceed with conducting further regulatory
activities to support NDA activities for the IV formulation, toxicology experiments will need to be conducted in animals. 
However, this can only proceed if the preliminary toxicology studies performed in vitro, as evaluated in the in vitro
study report (WBS 4.3, ***) demonstrate that the IV formulation is safe.