Exhibit 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 * * * 








 






    	Page 1 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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 * * * .







 


 






    	Page 2 of 20
	HHS0100201500007C
	November 3, 2017 



     

    



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 * * * .


 




 






    	Page 3 of 20
	HHS0100201500007C
	November 3, 2017 



     

    



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 * * * .







 


 






    	Page 4 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.


 






    	Page 5 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.


 






    	Page 6 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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:


 


	 	•	* * * 



	 	•	* * * 



	 	•	* * * 



	 	•	* * * 







 

 






    	Page 7 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.







 


 






    	Page 8 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.







 


 






    	Page 9 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


	1.8.3.	* * * 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.







 


 






    	Page 10 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


	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


 






    	Page 11 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


	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 * * *







 




 






    	Page 12 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


	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:


 






    	Page 13 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


	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	* * * 	* * * 


 














    	Page 14 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


	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.






 






    	Page 15 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 





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.







 


 


 

 






    	Page 16 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


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	* * * 	* * * 







 

 






    	Page 17 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 





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








 






    	Page 18 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 

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.


 






    	Page 19 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


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.


 


 


 


 


 


 


 






    	Page 20 of 20
	HHS0100201500007C
	November 3, 2017 



     

    

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.





 

 


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







 


 










 






    	Page 1 of 5
	HHSO100201500007C
	November 3, 2017 



     

    

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

	 	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	* * * 	* * * 




 


 







 






    	Page 2 of 5
	HHSO100201500007C
	November 3, 2017 



     

    

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

	 	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







 







 






    	Page 3 of 5
	HHSO100201500007C
	November 3, 2017 



     

    

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

	 	 	 	 	 	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
	November 3, 2017 



     

    

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


 







 


 


 


 


 


 


 





	Page 5 of 5
	HHSO100201500007C
	November 3, 2017