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Dependent on prior activities, AAV2 and/or AAV8 engineered capsids may be included in this step. AbbVie will also screen capsids in rodents (n=3-10) and rabbits (n=3-10); continued screening in these animals will be further evaluated and refined by RWG. Animals will be dosed at AbbVie facility, with vector provided by ... |
Capsida will be responsible for engineering strategy, virus library generation, vector production and QC, benchmarked vector genome residence, analysis of DNA biodistribution in the tissues, and FTO search of capsids nominated for the Final Pooled Candidate Identification Study. FTO search may occur prior to or in para... |
Capsida anticipates that top performing capsids from Final Variant Optimization could be sufficiently optimized to move into a third Pooled Candidate Identification study. Decision to move to the Final Pooled Candidate Identification study will be based on available data. The RWG will recommend to JGC whether to move t... |
Following data readout from this study, AbbVie can select up to 5 Reserved Capsids per route of administration (IVT, SCS, and IC). For clarity, if IVT route is used at this stage as a surrogate for IC, Reserved Capsids for IC route of administration will be selected based on anterior distribution of IVT-delivered capsi... |
VII. Final Pooled Candidate Identification Studies – IVT, SCS, and/or IC as agreed by the JGC |
JGC will agree on the top performing capsid variants from Final Variant Optimization (and potentially earlier rounds) delivered via IVT administration which will be tested in a Final Pooled Candidate Identification Study with a tagged cargo that is representative of the final cargo (either the final cargo or a surrogat... |
AbbVie and Capsida will screen capsids in rodents (n=3-10) and rabbits (n=3-10); continued screening in these animals will be further evaluated and refined by RWG. Animals will be dosed at AbbVie facility, with vector provided by Capsida. NHP (n=3) in-life to be 3-8 weeks. |
Each study will assess DNA biodistribution, benchmarked vector genome residence, single cell RNA expression as appropriate, gross transduction in target tissues, capsid quality attributes, and ocular tolerability / safety as appropriate. Teams to further clarify in vivo protein expression evaluation and assessment of i... |
Capsida will be responsible for vector production and QC, benchmarked vector genome residence, analysis of DNA biodistribution in the tissues, capsid quality attribute assessments, and in vitro immunogenicity assays. Capsida and AbbVie will be responsible for ex vivo immunogenicity assays if needed as described in Tabl... |
Following data readout from this study, AbbVie can select up to 5 Reserved Capsids per route of administration (IVT, SCS, and IC). For clarity, if IVT route is used at this stage as a surrogate for IC, Reserved Capsids for IC route of administration will be selected based on anterior distribution of IVT-delivered capsi... |
VIII. Single Variant Characterization Studies – SCS, IVT, IC |
A subset of reserve capsids will be evaluated in a Single Variant Characterization study delivered via SCS, IVT, and IC administration with a tagged cargo representative of the final cargo or optimized therapeutic cargo if available. |
It may be possible to evaluate one capsid in each eye. The Single Variant Characterization Studies will have an objective to confirm properties of capsid candidates including but not limited to the tissue biodistribution, cell type specificity, transduction, duration of expression, and immunogenicity. In some cases the... |
Animals will be dosed at AbbVie facility, with vector provided by Capsida. This study will evaluate up to 5 engineered capsids and parental serotype(s) in NHPs, i.e., n=up to 18 per route of administration. In-life to be 3-8 weeks. RWG may decide to conduct Single Variant Characterization study in rodents and/or rabbit... |
Data to be assessed include DNA biodistribution, single cell RNA expression in NHPs, transduction in target tissues in NHPs, ocular tolerability/safety, ex vivo immunogenicity assays, and clinical pathology in NHPs. Teams to further clarify in vivo protein expression evaluation as part of RWG discussions. Histopatholog... |
Capsida will be responsible for vector production and QC, analysis of DNA biodistribution in the tissues, capsid quality attribute assessment, and packaging efficiency and stability assays. Capsida and AbbVie will be responsible for their respective activities related to the ex vivo immunogenicity assays as described i... |
Data generated by Single Variant Characterization Study on capsids delivered via SCS, IVT, and IC will inform AbbVie's determination of AbbVie Selected Ophthalmology Capsids. |
IX. AbbVie Cargo and Expression Elements Improvement Activities |
During the Research Plan, AbbVie may further improve the AbbVie Ophthalmology Cargo and Expression Elements as necessary. In support of these activities, Capsida will provide vector for these evaluations and expert opinion. |
X. Vector Optimization |
AbbVie may conduct preliminary assessment of the efficacy of various vector designs to inform the choice of cargo for the Single Variant Characterization Studies. AbbVie will transfer the AbbVie Cargo sequence to Capsida for research grade production with different gene regulatory elements. Packaged virus will be trans... |
XI. Process and Analytical Development, Scale-up and Supply |
Capsida will provide non-GLP supply (research grade material) for discovery and preclinical research. Upon opt-in of AbbVie Selected Ophthalmology Capsids, Capsida will initiate process development activities shown below for up to a total of 3 programs (one per target, i.e. the lead) in support and as required to gener... |
The FDA guidelines for cellular and gene therapy products recommends multiple CMC-related activities to characterize product quality and manufacturing controls, to assure identity, purity, sterility and stability of products to certify lot release and establish product dating and shelf life. If Capsida is the site of m... |
AbbVie will take primary responsibility for developing the potency assay for quantifying the transducibility and efficacy of the protein produced from a specific lot of product. If Capsida produces material for clinical supply, AbbVie will transfer the assay and reagents to Capsida for validation. Other assays necessar... |
The cargo sequence will be transferred to the process development team and synthesized in a plasmid backbone suitable for manufacturing. Positive control material will be generated using the selected capsid and cargo to serve as a reference control for analytical development activities and evaluate process fit in each ... |
Table 2 - Data Package Elements - Library Screening and Variant Optimization (Round 1 and Round 2)* |
Category Analysis Assay Results Responsible Party NHP Benchmarked vector genome residence -target tissues Viral DNA amplified for NGS by PCR Capsida Biodistribution -target tissues Viral DNA assayed for total copy number via qPCR or ddPCR, with a preference for ddPCR in later studies Capsida Rodent Benchmarked vector g... |
*RWG may augment to include single cell RNA sequencing and RNA analysis as appropriate. Single cell RNA sequencing requires additional method development. |
Note, FTO search to be conducted prior to or in parallel with pooled CI study. |
Table 3 - Data Package Elements – First and Secondary Pooled Candidate Identification Studies for each of SCS, IVT, and IC |
Category Analysis Assay Results Responsible Party NHP Benchmarked vector genome residence of each variant Viral DNA amplified for NGS by PCR Capsida Biodistribution Viral DNA from the pool as a whole assayed for copy number per diploid genome via qPCR from tissues also characterized via NGS Capsida Protein expression T... |
*Immunogenicity assays are optional and would be conducted as agreed by RWG, and may be utilized in investigational manner. |
**FTO search to be conducted by Capsida prior to or in parallel with pooled CI study. |
Note: Capsid specific binding antibody assay, neutralizing antibody assay, and IFN-y ELISpot can be tech transferred after selection of development candidate. |
Table 4 –Final Pooled Candidate Identification Studies for each of IVT, SCS, IC |
Category Analysis Assay Results Responsible Party NHP Benchmarked vector genome residence of each variant Viral DNA amplified for NGS by PCR Capsida Biodistribution Viral DNA from the pool as a whole assayed for copy number per diploid genome via qPCR from tissues also characterized via NGS Capsida Protein expression T... |
*Immunogenicity assays with exception of in vitro assays on individual capsid candidates are optional and would be conducted as agreed by RWG, and may be utilized in investigational manner. |
**In vitro immunogenicity assays and in silico T cell epitope prediction would be conducted in parallel with in-life for this study as part of risk assessment. |
***FTO search to be conducted prior to or in parallel with pooled CI study. |
Note: some immunogenicity in vitro assays are still under development and will be completed prior to completion of pooled candidate identification study. For all in vitro assays, outputs include analysis of cell death and multiplex cytokine response. Capsid specific binding antibody assay, neutralizing antibody assay, ... |
Table 5 –Final Ophthalmology Data package Elements - Single Variant Characterization Studies for each of SCS, IVT, and IC |
Category Analysis Assay Results Responsible Party NHP Biodistribution Viral DNA assayed for copy number per diploid genome via qPCR from tissues also characterized via NGS Capsida Protein expression To be further clarified and agreed upon by RWG (e.g. western blot, IHC, or ELISA) AbbVie Single cell RNA sequencing Chara... |
*To be conducted in parallel with in-life for Single Variant Characterization Study |
Note: Capsid-specific binding antibody assay, neutralizing antibody assay, and IFN-y ELISpot can be tech transferred after selection of development candidate. |
Budget |
Exhibit E Initial Target List |
# Gene Target Name Aliases Gene ID Notes: |
1 SEMA3A Semaphorin3A 10371 |
2 RTN4R Reticulon 4 Receptor NOGOR 65078 |
3 OSMR Oncostatin M OSM 9180 |
4 NTRK1 Neurotrophic Receptor Tyrosine Kinase 1 TRKA, TRK1 4914 |
5 NTRK2 Neurotrophic Receptor Tyrosine Kinase 2 TRKB 4915 |
6 CNTFR Ciliary Neurotrophic Factor Receptor CNTFR-alpha 1271 |
7 GFRA1 GDNF Family Receptor Alpha1 2674 |
8 C5 Complement Component 5 727 |
9 CFI Complement Factor I 3426 |
10 RGMa Repulsive Guidance Molecule BMP Co-Receptor A 56963 |
11 ANGPT2 Angiopoietin 2 285 |
12 TEK Tyrosine Kinase with Ig and EGF Homology Domains-2 Tie2 7010 |
13 APOE Apolipoprotein E 348 |
14 MMP1 Matrix Metalloproteinase 1 CLG, CLGN 4312 |
15 MMP9 Matrix Metalloproteinase 9 CLG4b, GELB 4318 |
16 MMP3 Matrix Metalloproteinase 3 4314 |
17 FASLG Fas Ligand CD178, CD95L, TNFSF6 356 |
18 TREM2 Triggering Receptor Expressed on Myeloid Cells 2 54209 |
19 DCN Decorin 1634 |
20 |
1 |
SCHEDULE 1.56 |
Trademarks and logos |
Logo: |
Trademark: |
Capsida Biotherapeutics trademark filed (pending): WIPO Ref. 1424582701 |
1 |
SCHEDULE 1.75 |
B10, B22, C1, C2, C3 |
1 |
SCHEDULE 1.88 |
FTE Rate |
Research & Discovery: $425,000 Development: $375,000 Manufacturing: $375,000 Commercial: $425,000 Med Affairs: $350,000 |
1 |
SCHEDULE 5.1.2 |
Existing CMO Agreements |
Vendor Name Type of Agreement Description Assignable / Sublicensable |
DNA TwoPointO Inc (ATUM) Material Transfer Agreement with workorders under MTA Plasmid synthesis Assignable by Capsida |
Aldevron Master Services Agreement with workorders under MSA Plasmid production Assignment requires written consent (Capsida standard terms) |
Charles River Master Services Agreement with workorders under MSA QC Testing / Release Assignment requires written consent (Capsida standard terms) |
Millipore Sigma (BioReliance Corporation) Master Services Agreement with workorders under MSA QC Testing / Release Assignment requires written consent (Capsida standard terms) |
KBI Master Services Agreement with workorders under MSA Analytical services Assignment requires written consent (Capsida standard terms) |
AdVec License 293 cells Can sublicense with written permission from AdVec |
Life Tech / Thermo License HEK293 GMP cells Can sublicense for a fee |
1 |
SCHEDULE 6.3.3 |
Co-Promotion Readiness Plan |
Elements of Co-Promotion Readiness Plan |
A. Elements of Co-Promotion Readiness. The Co-Promotion Readiness Plan prepared by Capsida and provided to AbbVie pursuant to Section 6.3.3(a) must contain all of following elements to demonstrate that Capsida will have adequate resources and expertise to co-promote the Co-Promotion Product during the applicable Co-Pro... |
1. Upon delivery by Capsida to AbbVie of the Co-Promotion Option Exercise Notice for the Co-Promotion Product and the Co-Promotion Readiness Plan, Capsida must have: a. Hired a Chief Commercial Officer or equivalent position, which individual has adequate prior experience managing the promotion of a neurological diseas... |
2. Upon delivery by Capsida to AbbVie of the Co-Promotion Option Exercise Notice for the Co-Promotion Product and the Co-Promotion Readiness Plan, or, if such Exercise Notice occurs before the delivery by AbbVie to the JGC of the ALS Commercialization Plan, within sixty (60) days of delivery by AbbVie of such plan, the... |
3. At the United States BLA submission date for the Co-Promotion Product, the foregoing elements (in items 1 and 2) must continue to be satisfied and Capsida must have: a. A functioning sales force operations system that is consistent with industry practice and capable of tracking and measuring complete sales force met... |
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