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mP53 |
CEBPB |
ΔNTP63 |
Tenascin C |
Exhibit B-1 Initial Collaboration Plan |
Introduction The following is an outline of the research plan for the early-stage discovery partnership between AbbVie and Anima. This Research Plan covers three Collaboration Targets, NRAS, (melanoma, NSCLC, AML), FOXA1 (breast and prostate cancer) and BRD2 (IPF). This Research Plan could also potentially apply to fou... |
Description of Research Plan Activities 1. HTP Screening System Development (5 months) 1.1. Anima: 1.1.1. Primary, Translationlight assay development (384-well plate) 1.1.1.1. Commercially available cell lines (with recommendations from AbbVie) 1.1.1.1.1. NRAS Q61XNCI-H2087, NCI-H1299, SW1271, SKMEL2, IPC298 or SKMEL30... |
1.1.3.2. Image and data analysis integration (Training of Anima's algorithm for detection of differences in Translationlight signal in assay system) 1.1.4. Secondary/downstream assay development (to be developed in parallel to primary assay development and finalized during image and data analysis) (est. 9 months in tot... |
2. Translationlight Screen (High-Throughput Screening and Image Analysis) (3 months) 2.1. Anima 2.1.1. Screen compound library #5 (~300K compounds) 2.1.1.1. Experimental phase (8 weeks) 2.1.1.2. Image acquisition and upload 2.1.2. Image and data analysis (Includes flagged wells and Translationlight score) 2.1.3. Partic... |
3. Hit Confirmation and Validation (selection of series to advance to Lead Generation) (10 months) 3.1. Anima: 3.1.1. Hit confirmation (selection of target-specific small molecule hits) 3.1.1.1. Compound re-order (from powder) and QC 3.1.1.2. Re-test in primary Translationlight assay at a single concentration 3.1.1.3. ... |
3.1.2.2.3. Target-centric assay in primary cells used for the screen and additional cellular environment(s) (dose-response, time course, with detection of protein levels or activation/inhibition of downstream pathways). 3.1.2.3. MoA Studies: Target timing (Profiling compound(s) activity on target mRNA and protein half-... |
4. Lead Generation (LG) (18 months) 4.1. Anima: 4.1.1. Compound re-synthesis and activity validation 4.1.1.1. Re-synthesized compounds will be assessed in key target-specific assays. At the end of this stage, up to 3 clusters will be selected for Lead Generation. 4.1.1.2. Transcriptomics and proteomics (effect on globa... |
5. Lead Optimization (18 months) 5.1. Anima: 5.1.1. Chemistry design (synthesis cycles, SAR analysis, in vitro and in vivo ADME to improve efficacy and/or ADME properties of current lead series) 5.1.2. Encumberment re-assessment 5.1.3. Compound SAR studies (Target-based and cell-based assays will be used. Mode of actio... |
6. Candidate Nomination 6.1. Anima: 6.1.1. Participation in JGC 6.2. AbbVie: 6.2.1. Non-GLP Tox and dose range finding 6.2.2. Non-GLP CV safety 6.2.3. Human dose prediction and DDI projection 6.2.4. Pre-formulation 6.2.5. Plan for API synthetic route 6.2.6. Chemical stability assessments 6.2.7. Participation in JGC |
7. Candidate Selection 7.1. Anima: 7.1.1. Participation in JGC 7.2. AbbVie: 7.2.1. Stability assessment of API to support future clinical formulation 7.2.2. Clinical formulation for FIH 7.2.3. Assessment of needs for backup 7.2.4. Develop and validate clinical translatable biomarker 7.2.5. Refinement of human dose proj... |
8. IND-Enabling Package 8.1. Anima: 8.1.1. Participation in JGC 8.2. AbbVie: 8.2.1. DMPK 8.2.1.1. Single dose PK 8.2.1.2. Formulation effects and dose escalation PK 8.2.1.3. In vitro ADME profiling 8.2.1.4. Bioanalytical method validation (tox species and human) 8.2.2. Pre-Clinical Safety 8.2.2.1. non-GLP dose-range fi... |
Proposed Research Plan Timeline |
Exhibit B-2 Cost of Activities for Collaboration Plans |
# Activity Budget ($) |
Hit Validation Stage |
Phenotypic Screening System Development |
1 Purification, labeling and QC of tRNA pairs 134,000 |
2 Profiling tRNA and mRNA in target cells 198,000 |
3 Translationlight optimization 194,000 |
4 Translationlight validation (for example, siRNA) 172,000 |
5 Assay transfer to HCS 160,000 |
6 HCS assay validation 168,000 |
7 Secondary/ assay development 164,000 |
8 RNAi translation library 158,000 |
9 Data analysis 160,000 |
Assay validation for Phenotypic Screening start |
Screen (200K) |
10 Data generation – TranslationLight screen 350,000 |
11 Image & Data analysis 118,000 |
Hit confirmation |
12 Compound order, shipment, and QC 80,000 |
13 Data generation: IF 135,000 |
14 Data generation: Translationlight global 135,000 |
15 Data generation: Translationlight specific 135,000 |
16 Image & Data analysis 110,000 |
17 Chemistry analysis 125,000 |
Hit Validation and Expansion |
18 Compound order, shipment and QC 80,000 |
19 Target Timing - Protein 165,000 |
20 Target Timing - RNA 165,000 |
21 Data generation: IF, Dose response 115,000 |
22 Data generation: Translationlight specific 130,000 |
23 Pixcell translation 120,000 |
24 Pixcell RNA and/or mRNA Regulation Reporter (m3R) 153,000 |
25 Efficacy in non-screen cells and cytotox assays 141,000 |
26 Image & Data analysis 110,000 |
27 Chemistry analysis 125,000 |
Hit Validation total budget 4,000,000 |
*The cost of unperformed activities as described in Section 7.3.1 (Collaboration Target Substitution Fee) will be calculated as the difference between the Hit Validation total budget ($4,000,000)and the sum of the budgeted costs of all tasks completed in the Hit Validation stage. |
# Activity Budget ($) |
Lead generation stage |
1 DESIGN-Make-ADME cycle 1 196,000 |
2 Primary cellular assay cycle 1 102,000 |
3 Data & chemistry analysis cycle 1 75,000 |
4 DESIGN-Make-ADME cycle 2 196,000 |
5 Primary cellular assay cycle 2 102,000 |
6 Data & chemistry analysis cycle 2 75,000 |
7 DESIGN-Make-ADME cycle 3 196,000 |
8 Primary cellular assay cycle 3 102,000 |
9 Data & chemistry analysis cycle 3 75,000 |
10 DESIGN-Make-ADME cycle 4 196,000 |
11 Primary cellular assay cycle 4 102,000 |
12 Data & chemistry analysis cycle 4 75,000 |
13 DESIGN-Make-ADME cycle 5 196,000 |
14 Primary cellular assay cycle 5 102,000 |
15 Data & chemistry analysis cycle 5 75,000 |
16 DESIGN-Make-ADME cycle 6 196,000 |
17 Primary cellular assay cycle 6 102,000 |
18 Data & chemistry analysis cycle 6 75,000 |
19 DESIGN-Make-ADME x cycle 7 196,000 |
20 Primary cellular assay cycle 7 102,000 |
21 Data & chemistry analysis cycle 7 75,000 |
22 DESIGN-Make-ADME cycle 8 196,000 |
23 Primary cellular assay cycle 8 102,000 |
24 Data & chemistry analysis cycle 8 75,000 |
25 Disease relevant cellular assay cycle #1 193,000 |
26 Disease relevant cellular assay cycle #2 193,000 |
27 Disease relevant cellular assay cycle #3 193,000 |
28 Disease relevant cellular assay cycle #4 193,000 |
29 Disease relevant cellular assay cycle #5 193,000 |
30 MOA (Proteomics and transcriptomics) 217,000 |
31 MOA (Pixcell - Translation) 186,000 |
32 MOA (Pixcell - TranscriptLight) 186,000 |
33 Chemical proteomics (ABPP and/or CETSA) 194,000 |
34 Cellular safety study – cycle #1 112,000 |
35 Cellular safety study – cycle #2 112,000 |
36 Cellular safety study – cycle #3 112,000 |
37 Cellular safety study – cycle #4 112,000 |
38 Kinase Panels 85,000 |
39 Safety panels 44 55,000 |
40 PK (single and repeated) 122,000 |
41 Animal model cluster 1 186,000 |
42 Animal model cluster 2 186,000 |
43 Animal model cluster 3 186,000 |
Lead Generation total budget 6,000,000 |
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