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.

EX-10.1 2 exh_101.htm EXHIBIT 10.1 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

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

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

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