Milestone and Deliverables Chart for HHSO100201500007C Clinical Trial Material Manufacturing and Development

Summary

This document outlines the milestones, deliverables, and success criteria for a contract between a contractor and the U.S. Department of Health and Human Services (HHS), specifically under contract HHSO100201500007C. It details the required steps for manufacturing clinical trial materials, commercial scale-up, nonclinical toxicology studies, and in vitro experiments for the drug BCX4430. The chart specifies key reports, manufacturing batches, and studies that must be completed, along with approval and quality requirements, to advance through each project phase.

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