exh_101.htm


Exhibit 10.1


 






 




  





  











  









 




  





  











  







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


May 7, 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


	
1.6.2

	
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.


 






	
1.6.3

	
Prepare a Campaign Summary Reports

	
Campaign Reports (CTM Batches ***)

	
Completion of DP Campaigns

	
***

	
N/A


	
1.6.4

	
Drug Product stability study

	
Initial Report on stability activities

	
Stability Data

	
***

	  
	
1.6.5

	
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


	
1.7.2

	
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


	
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





 




  





  











  





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.


 






	
2.4.2


 

	
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 - IM


Go/No Go Criteria to Initiate: WBS 1.4.1 Completion of Manufacture cGMP BCX4430 (*** campaign DS Batch ***)


	
3.1.1

	
Complete GLP *** IM Tox Study - ***

	
Study Report

	
Established NOAEL

	
***

	
Drug Substance confirming to release criteria


	
3.1.2

	
Complete GLP *** IM Tox Study - ***

	
Study Report

	
Established NOAEL

	
***

	
Drug Substance confirming to release criteria


	
3.2.1

	
Conduct *** assessment in *** and ***

	
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


	
CLIN 0004 – IN VITRO EXPERIMENTS – IV


Go/No Go to Initiate: WBS 1.5.8 Completion of Excipient compatibility studies for IV formulation


	
4.1.

	
Conduct *** Test – IV

	
Study Report

	
No effect on ***

	
***

	
IV formulation WBS 1.5.8


	
4.2.

	
Conduct *** Test – IV

	
Study Report

	
No effect on ***

	
***

	
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.


 






	
4.3

	
*** IV experiments

	
Study report on all *** assays with recommendation to proceed CLIN0005

	
No toxicology ***

	
***

	  
	
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