Transcript The Company - Biopercept
B
i
oPercept AB
innovative imaging solutions
Enabling for the first time rapid and general radiolabelling of biologicals
27-Apr-20 • About us • RadTag technology • Proof of concept 1
Samuel Svensson, PhD • Principal scientist AstraZeneca R&D. Professor of pharmacology, LiU. Project leader for three PET ligand projects to FTIM (AZD2184, 2995, 4694).
Peter Ström, MSc • Radiochemist with 20+ years experience within AstraZeneca. Carl M Andersson, PhD, associate professor • Organic chemist. Consultant with 20+ years experience from senior managerial positions within biotech and pharma.
Asset: ”Agents and methods for visualising analytes” PCT/EP2011/070172 . IPR fully owned by BioPercept AB.
27-Apr-20 2
Growing market potential for PET radioligands
2010: Lilly acquires Avid Radiopharmaceuticals for an upfront $300 million and $500 million in additional payments 2011: Navidea acquires AZD4694, an amyloid imaging PET ligand from AstraZeneca
27-Apr-20 3
Biologicals are must have for pharma Radiolabelling within development of biologicals very limited -- lack of generalised radiochemical methodology Six out of 21 new approvals by the FDA were for biologicals in 2010 -- share will increase; typical ambition calls for 30-40% of pipeline Increasing demand for ability to monitor, visualise, perform PK studies and implementing personal health care Biosimilars market estimated at USD 4,000 million in 2017 RadTags suggest a new paradigm 27-Apr-20 4
FlAsH technology – a fluorescence labeling technology developed for live cell imaging (R Tsien Nobel prize 2008) FlAsH-based protein detection available from
Easily constructed six-amino acid tags The CCPGCC tag can be incorporated by standard techniques – During peptide synthesis – Using Polymerase chain reaction (PCR) – Using cloning vectors commercially available from Life Technologies Gene CCPGCC tag (in frame) Promotor Expression vector
RadTags bind to same consensus sequence as FlAsH 7 27-Apr-20
RadTags enable radiolabelling using different isotopes at the same site Precursor for 18 F, 121 I, 125 I, 131 I, 27-Apr-20 Precursor for 13 C, 14 C, 11 C, 3 H, 19 F 8
Fit-for-purpose radiolabelling of biologicals using identical RadTags 3 H 14 C 18 F 27-Apr-20 9
(1) (2) (3) +
Peptide Radtag Radtag-peptide
Molecular structure of a RadTag and RadTag bound to target protein sequence ( CCPGCC-). The graphs show HPLC peaks of peptide (1), RadTag (2), and RadTag covalently bound to peptide (3). Peptide-RadTag stable at RT.
Peptide [ 3 H]RadTag-peptide [ 3 H]RadTag + Peptide (in excess) incubate 3 uv H [ 3 H]RadTag-peptide + Peptide (free) purify (HPLC) Reaction mix: peptide & [ 3 H]RadTag-peptide uv [ 3 H]RadTag-peptide 3 H MS ID on radio peak confirms [ 3 H]RadTag-peptide 27-Apr-20 Pure [ 3 H]RadTag-peptide following HPLC 11
RadTags simplify radiolabelling of biologicals Enabling • Increased flexibility and specific binding • Stable binding – small tag size reduces interference with target protein • PKPD studies with labelled proteins • Microdosing diagnostics (peptides/antibodies) • Quantitative autoradiography • Companion diagnostics • Potential for pretargeting 27-Apr-20 12
PoC study I Melanoma tumors
Ac-Nle-Asp-His-(D)Phe-Arg-Trp-Gly-Lys-Arg-Trp-Cys-Cys-Pro-Gly-Cys-Cys-Lys-Thr-Phe
MW
a
MSH 2614g/mol RadTag 480 g/mol
O N H O H N O N H OH N O H N NH O N H H N NH NH 2 O H N O N H NH O H N O O N H H N NH NH 2 O H N O SH H N N H NH O NH 2 H O O H N H O O N H O N SH O O NH O H N H N O NH SH O H S NH 2 27-Apr-20
Cheng et al J Nucl Med 2007; 48:987–994
13
PoC study II Breast cancer tumors Molecular imaging for personalized & targeted anticancer therapy Trastuzumab (Herceptin) (Roche) 111 In-DPTA-trastuzumab 111 In-DPTA-trastuzumab (Fab) 89 Zr-trastuzumab 64 Cu-DOTA-trastuzumab (Fab) 89 Zr-trastuzumab 99m Tc-MORFs-streptavidin-trastuzumab 18 F-MORFs-streptavidin-trastuzumab 27-Apr-20 14
Financing and partners • Innovationsbron • Innovationskontoret, LiU • Competence Network AB, Södertälje • TBD Biodiscovery, Estonia • Selcia Ltd, UK • Maria Swartz Innovationskontoret LiU • Prof Peter Konradsson, LiU 27-Apr-20 15