08003000X15801S
BASE PERIOD Immunogenicity and primary platform development Rabies Virus Based Platform Vaccines. RABV constructs (FILORAB 1-3) expressing EBOV GP, SUDV GP or MARV GP have been recovered, clone purified and Master Virus Seed (MVS) have been prepared.. The gene encoding LASV GPC has been cloned, inserted into the RABV vector and successfully recovered in VERO cells. Contractor shall characterize the cDNA clones and shall send to subcontractor for GMP production of Master Seed Viruses. The contractor shall prepare, inactivate and purify FILORAB1 - 3 and LASSARAB at research scale. Contractor shall use the produced viral stocks for the NHP immunogenicity studies. The contractor shall provide the subcontractor with research scale viral stocks for formulation studies. Contractor shall FILORAB1 Development material is available for formulation development and NHP studies. Contractor shall ensure FILORAB2 Development material is available for formulation development and NHP studies. Contractor shall ensure FILORAB3 Development material is available for formulation development and NHP studies. Contractor shall ensure LASSARAB Development material is available for formulation development and NHP studies. Preparation of Seed Lot Materials. Contractor shall provide the Master Cell Bank for Vero cells. Master Virus Banks for FILORAB 1 3 have already been prepared. Contractor shall prepare a Master Virus Bank for LASSARAB (by rescue of the cDNA clone) under GMP. Contractor shall ensure that the LASSARAB bank will be produced. Contractor shall commence Project implementation Contractor shall prepare starting materials and seed banks. Preparation of non-GMP lot of GLA-SE. Contractor shall provide GLA salt and shall produce an engineering lot of GLA-SE. Contractor shall ensure that GLA-SE will be prepared for pivotal NHP immunogenicity and challenge studies and pivotal GLP toxicology study. Contractor shall conduct Bulk GLA salt production. Contractor shall conduct GLA-SE Lot Production. Contractor shall conduct Lot release testing. Immunogenicity of Single, Trivalent, and Tetravalent Vaccine in NHPs. Contractor shall perform an NHP safety and immunogenicity study with laboratory research viral lots to confirm induction of immune responses to monovalent FILORAB 1- 3 and LASSARAB, the trivalent mixture of FILORAB1-3 and the tetravalent FILORAB 1-3 and LASSARAB vaccine. The contractor shall provide study protocols to NIAID for review before initiation of the studies. Contractor shall obtain NIAID protocol review/approval and sourcing of animals. OPTION 1 Testing of Seed Lot Materials Testing of Seed Lot Materials. The contractor shall test each Master Virus Seed Bank of FILORAB 1; 2; 3 and LASSARAB for purity, content and identity. Contractor will provide test protocols to NIAID for review before initiation of the studies. The tests will include sterility, mycoplasma tests, and tests for other extraneous agents to meet FDA testing requirements. Contractor shall perform Testing of Master Virus Seed Bank FILORAB 2, 3, and LASSARAB ( Syn. BNSP333-GPLV). Contractor shall perform Qualification of VERO WCB P 144 for development and GMP manufacturing. Deliverable The Contractor will ensure that qualification of all four Master Seed Banks is completed and will provide documentation of testing results. OPTION 3 Upstream and Downstream Process Development for Monovalent Drug Substance Manufacture. Upstream and Downstream Process Development for Monovalent Drug Substance Manufacture. Upstream and downstream processes have been well-defined for FILORAB1 and 2 by the contractor. The contractor shall optimize processes for the production of FILORAB2, FILORAB3, and LASSARAB, with attention to the virus inactivation steps and generation of draft Batch Records for production of each monovalent bulk drug product. Process engineering Contractor shall perform Optimization of FILORAB3 production processes. Contractor shall perform
IDT Biologika GMBH
Definitive Contract HHSN272201700082C
$32.9m 9/23/21 08003000X15801S
Subcontractor (Exxell BIO) shall perform a supporting role on all of the Tasks listed below. We will not be providing the final deliverables directly, but shall be assisting by writing documents, reviewing documents, editing documents, suggesting experimental and clinical protocols, reviewing results and coordination with other subcontractors as appropriate in the complete deliverables by TJU, IDRI and IDT. 1.1 Task 1 - Rabies Virus Based Platform Vaccines (TJU) 1.1.0 Subcontractor shall provide the Technology License Fees payable to NIH/OTT as required by NIH/OTT 1.1.1 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure that the FILORAB1 Development material is available for formulation development and NHP studies 1.1.2 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure that the FILORAB2 Development material is available for formulation development and NHP studies 1.1.3 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure that the FILORAB3 Development material is available for formulation development and NHP studies 1.4 Task 4 - Immunogenicity of Single, Trivalent, and Tetravalent Vaccine in NHPs (TJU) 1.4.1 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the completion of Source Animals 1.4.2 Subcontractor shall provide ongoing consultation with thewith the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the Study initiation 1.4.3 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the initiation of Immunization #2 1.4.4 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the initiation of Immunization #3 1.4.5 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the Serum Collection 1.4.6 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the Sample Analysis 1.4.7 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents to ensure the completion of the Study Report 1.5A Task 5A - Pre-formulation Development (IDRI, TJU, IDT) 1.5.1 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the Preformulation Development for FILORAB2 1.5B Task 5B - Preformulation Development part B 1.5.2 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the Preformulation Development for FILORAB3 1.5.3 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the Preformulation Development for FILORAB4 1.5.4 Subcontractor shall provide ongoing consultation with the Contractor including review and editing of documents and coordination with other subcontractors where appropriate to ensure the Preformulation Development for
Exxell Bio Inc.
Definitive Contract HHSN272201700082C
$742.1k 10/20/20 08003000X158XXS
3.1 PRE-FORMULATION & IDEATION Lead formulation and analytical scientists will be appointed to the program on signing the proposal. They will be responsible for working up the formulation and analysis strategy in more detail, in combination with Thomas Jefferson University. They may conduct the following activities to support the product development program. â ¢Develop technical risk analysis assessments â ¢Understand the health and safety precautions needed â ¢Literature searching â ¢Procure and acquire appropriate materials to conduct the planned stages Information gathered in this stage will be shared with Thomas Jefferson University. 3.2 DLS METHOD ACQUISITION/VERIFICATION It is assumed that Thomas Jefferson University has a suitable DLS method for the particle size analysis of the emulsion, which would be acquired for use in AMRI Glasgow. The method would be assessed on the basis of; â ¢System suitability â ¢Specificity â ¢Precision The exact testing procedure and pre-defined acceptance criteria would be detailed within the validation protocol and sent to the client prior to testing for review and approval. A final report would be compiled upon completion of the method verification. 3.3 FORMULATION/PROCESS ASSESSMENT Within the R & D laboratory and at a predefined small volume (TBC), AMRI Glasgow would prepare the 10% emulsion formulation. The existing Thomas Jefferson University process would be followed/adapted as appropriate. An outline work plan would be prepared and shared with Thomas Jefferson University ahead of lab activities. Throughout manufacture visual observations and activity durations would be monitored/recorded. As appropriate, bulk solution appearance, pH, particle size (DLS) would also be recorded. 3.4 FILTRATION ASSESSMENT Known volumes of emulsion would be passed, by peristaltic pump and platinum-cured silicone tubing, through proprietary 2 â Pâ (pharmaceutical) grade filter capsules of known surface area to assess adsorptive losses per cm of filter surface area on two types of membrane; e.g. PVDF (polyvinylidene fluoride) or PES (polyether sulfone). Ease of filtration, measured as the back pressure up-stream of the filter, would be assessed for each filter type. Particle size in the pre-filter and in the final bulk filtrate would be determined by DLS. The pH of the pre-filter and filtrate samples would also be determined. Note: as target particle size for stable emulsion is anticipated 120 +/- 40nm, it is anticipated that filtration processes will be relatively slow and may require additional assessment as a pressurised process. However the necessarility small volume requirements short term may be manageable. Decision point. From the data generated in the process assessment the need for adaptation would be discussed/agreed with Thomas Jefferson University. As required, further iterations could be undertaken should further refinement be needed. The scope of any additional experiments would be discussed with Thomas Jefferson University and captured in a separate change order. 3.5 NON-GMP TECHNICAL BATCH MANUFACTURE Two non-GMP technical batches of the following products would be carried out: 1)10% SE 2)10% SE mixed with 75 μg adjuvant (3D(6-acyl)-PHAD®) 3)10% SE mixed with 250 μg adjuvant (3D(6-acyl)-PHAD®) A target of 500 vials, each filled 0.5 mL is required; a suitable overage will be agreed. Each emulsion product would be manufactured using the formulation and process as identified in preceding stages. Technical Batch Records (TBRs) would be prepared to document the manufacture and support future technical transfer to GMP manufacturing. The executed TBR would be provided on completion of manufacture. Bulk formulation would be passed through a single sterile 0.45 µm and two sterile 0.22 µm (membrane TBD) filter capsules in series. Fill will be 0.5 mL per 2mL Scott Type 1 glass vial sealed with 13 mm bromobutyl Flurotec injection
Albany Molecular Research (Glasgow) LIMITED
Definitive Contract HHSN272201700082C
$2.1m 9/10/20 08003000X15801S
SCOPE OF WORK - IDRI 1.3 Task 3 - Preparation of non-GMP lot of GLA-SE (IDRI) 1.3.1 Bulk GLA salt production 1.3.2 GLA-SE Lot Production 1.SA Task SA - Pre-formulation Development (IDRI,TJU,IDT) l.S.l Preformulation Development for FILORAB2 1.SB Task SB - Preformulation Development part B l.S.2 Preformulation Development for FILORAB3 l.S.3 Preformulation Development for FILORAB4 l.S.4 Preformulation Development for Lassarab 1.6 Task 6 - Antigen Preparation and lmmunogenicity Assays 1.6.2 Task 6B - lmmunogenicity Assays (IDRI) 1.6.3 Assay Development Reports 1.11 Task 11- Drug Product Formulation Development for Tetravalent Vaccine {IDRI) 1.11.1 Screen tetravalent formulat ions with stabilizers 1.11.2 DOE to Optimize formulation 1.11.4 Manufacture formulations for stability studies 1.11.5 3-month Stability analysis and report 1.11.6 Tech Transfer of tetravalent formulation to IDT 1.11.7 lmmunogenicity verification studies 1.13 Task 13 - Pre-IND Meeting to Discuss Phase IClinical Trial Development Plan (IDRI, IMDZ, TJU, Exxell,IDT) 1.13.1 Prepare briefing package 1.13.2 Submit plND package to FDA 1.13.3 Receive responses from FDA 1.13.4 Conduct pre-IND meeting with FDA 1.16 Task 16 - Toxicology Study - GLP Repeat Dose Toxicity Study of LASSARAB, Trivalent FILORAB 1-3, and Tetravalent FILORAB 1- 3+LASSARAB (IDRI) 1.16.1 In-life study 1.16.2 Report generation 1.17 Task 17 - Preparation of GMP lot of GLA- SE (IDRI) 1.17.1 cGMP GLA salt production and release 1.17.2 cGMP GLA-SE Lot Production 1.17.3 Lot release testing 1.18 Task 18 - File IND (IDRI,IMDZ, TJU, Exxell, IDT) 1.18.1 Draft IND 1.18.2 Finalize IND Package 1.18.3 IND submitted to US FDA 1.18.4 Phl regulatory approvals obtained 1.19 Task 19 - Preparation for Phase IClinical Trial (IDRI) 1.19.1 NIAID Approval of Clinical Protocol 1.19.2 Site Selection and Startup 1.19.3 IRB Approval 1.2 Task 20 - Phase I Clinical Trial (TJU, Exxell, IDRI) 1.20.1 Cohort 1LASSARAB - lo Enrollment/Dosing 1.20.2 Cohort 2 LASSARAB - hi Enrollment/Dosing 1.20.3 Cohort 3 Trivalent - Enrollment/Dosing 1.20.4 Cohort 4 Tetravalent - lo Enrollment/Dosing 1.20.5 Cohort 5 Tetravalent - hi Enrollment/Dosing 1.20.6 Database Lock, immunogenicity and First interpretable results report 1.20.7 Final Clinical Study Report 1.20.8 Supplemental report of immunogenicity and safety results 1.21 Task 21- Stability of Materials Option Period 1 1.21.1 Stability of GLA-SE first lot 1.22 Task 22 - Stability of Materials Option Period 2 1.22.1 Stability of GLA-SE first lot 1.22.6 Stability of Development Tetravalent Drug Product 1.23 Task 23 - Stability of Materials Option Period 3 1.23.1 Stability of GLA-SE first lot 1.23.6 Stability of Development Tetravalent Drug Product 1.23.17 Stability of cGMP GLA-SE Lot 1.24 Task 24 - Stability of Materials Option Period 4 1.24.1 Stability of GLA-SE first lot 1.24.6 Stability of Development Tetravalent Drug Product 1.24.17 Stability of cGMP GLA-SE Lot
Access To Advanced Health Institute
Definitive Contract HHSN272201700082C
$12.5m 9/25/19 08003000X15801S
BASE PERIOD Immunogenicity and primary platform development Rabies Virus Based Platform Vaccines. Contractor shall support the Prime contractor through attendance of internal and external meetings as required. Contractor shall provide strategic and tactical advice based upon extensive experience in the discovery and advanced development of vaccines and therapeutics against highly pathogenic viruses. OPTION 6 - Efficacy of Trivalent Vaccine in NHPs Efficacy of Trivalent Hemorrhagic Fever Vaccine in NHPs. Contractor shall perform NHP safety, immunogenicity and challenge studies to confirm induction of protective immune response by manufactured monovalent FILORAB 1- 3 and by a trivalent mixture of FILORAB1-3. Specifically, TJU or its designee will perform all activities related to vaccinating the NHP, and then ship the NHP to USAMRIID when they are ready for challenge. The NHP will go directly into BSL-4 upon arrival at USAMRIID. Geneva/USAMRIID will work with TJU to provide study protocols and drafts of reports to NIAID for review. Prime Contractor shall source animals after NIAID review of study protocol. Prime Contractor shall conduct Study initiation. Prime Contractor shall conduct Immunization #1. Prime Contractor shall conduct Immunization #2. Prime Contractor shall perform Serum Collection. Prime Contractor shall conduct Sample Analysis. Challenge Study (performed by USMARIID) Contractor shall perform Challenge study. Contractor shall generate Top Line report. Contractor shall perform Pathology analysis. Contractor shall generate Final study report. Deliverable The contractor will deliver a final Study Report describing safety, immunogenicity and efficacy of monovalent FILORAB 1- 3 and of a trivalent mixture of FILORAB1-3. OPTION 15 - Efficacy of Tetravalent Vaccine in NHPs Efficacy of Tetravalent Hemorrhagic Fever Vaccine in NHPs. Contractor shall perform NHP safety, immunogenicity and challenge studies, to demonstrate induction of protective immune response by the formulated, tetravalent vaccine consisting of FILORAB1, 2, 3, LASSARAB and the adjuvant GLA-SE. The contractor will provide the NHP protocol to NIAID for review prior to initiation of the study. Specifically, TJU or its designee will perform all activities related to vaccinating the NHP, and then ship the NHP to USAMRIID when they are ready for challenge. The NHP will go directly into BSL-4 upon arrival at USAMRIID. Geneva/USAMRIID will work with TJU to provide study protocols and drafts of reports to NIAID for review. Prime Contractor shall Source animals after NIAID approval of the study protocol. Prime Contractor shall initiate Study. Prime Contractor shall conduct Immunization #1. Prime Contractor shall conduct Immunization #2. Prime Contractor shall conduct Serum Collection. Prime Contractor shall perform Sample Analysis. Challenge Study (performed by USMARIID) Contractor shall conduct Challenge. Contractor shall generate Topline study report. Contractor shall perform Pathology analysis. Contractor shall generate Final Study report. Deliverable The contractor will provide the Final Tetravalent NHP Study Report OPTION 20 - Phase I Clinical Trial Phase I Clinical Trial. Contractor shall support the Prime contractor through attendance of internal and external meetings as required. Contractor shall provide strategic and tactical advice based upon extensive experience in the discovery and advanced development of vaccines and therapeutics against highly pathogenic viruses.
The Geneva Foundation
Definitive Contract HHSN272201700082C
$11.0m 3/22/19