The reduced side effects of this approach allow access to a broader population of patients, including the very ill, the very young and the very old. Antibody Drug Conjugates (ADCs) have proven this concept utilizing antibodies as a carrier of the drug payload, entering the target cells and releasing the active ingredient “payload” after binding to surface tumor protein markers. As an alternative to antibodies Exeris selects well-known, natural protein ligands for cancer markers, rather than antibodies, as the drug carrier. The development of these Protein Drug Conjugates (PDCs) opens targeted drug delivery to a broader array of diseases. Exeris uses a systematic drug design process for PDCs targeting tumor cells in well-studied cancers with unmet need and where ADCshave failed. The process leverages state-of-the-art experimental and computational structural biology to rationally engineer the PDCs and organic synthesis for drug conjugation. The PDCs are tested in cellular assays, producing a dossier of pre-clinical data for each. With a B2B goal, successful PDCs can be designed as a service (Drug Design as a Service) or licensed to pharmaceutical companies for clinical development.
Protein Drug Conjugates
Targeted therapy
Targeted therapy delivers micro doses of therapeutic molecules directly to the diseased cells while limiting exposure of healthy cells.
Our Approach to Drug Conjugates
The Exeris scientists have extensive experience in protein conjugation, purification, and modification. For proteins that can be modified at the molecular level, we can use cysteine mutagenesis to introduce a single labeling site. For proteins that cannot be changed at the molecular level, we look for specific sites that can be modified using chemical methods (site-specific labeling). For proteins that have no site-specific labeling sites, we use controlled labeling of surface amines plus advanced purification to obtain single ratio conjugates or near homogeneous multiple ratio conjugates.
- Flexibility to attach payload via multiple methods.
- The conjugation strategy can be tweaked to allow coupling to different categories of compounds.
- Shortened timelines for the development of a bioconjugation strategy.
1. Target receptor selection based on
- Unmet medical need
- Specificity of receptor to tumor
- Technical features of the receptor
- Customer Brief
2. In silico design of the three dimensional structure of the receptor
3. In silico design of the protein or peptide ligand
- in vitro testing
4. In silico design of the optimal positioning of the linker and payload
- interactive, high-throughput 3D modeling
5. Transfer one or more candidate structures to mammalian or E. coli for production
- In vitro testing
- Affinity for receptor
6. Lab scale production of conjugate of ligand with linker and payload
- In vitro testing
- Affinity for receptor
- Ability to deliver payload
7. Pre-clinical campaign (Design Optimization)
- Multiple drug conjugation strategies for each protein carrier
8. Partnering and licensing
Our strength in the field of conjugates
Exeris expertise in computational biology and structural biology enables a practical approach to the design of therapeutic conjugates. Our research excellence can be offered as a service for bio-pharmaceutical companies that develop recombinant proteins as therapeutics. New, target-specific protein drugs can be developed by conjugating drugs or toxins to recombinant proteins. We can also chemically modify or process your recombinant proteins for better clinical performance. Exeris scientists have extensive experience in protein conjugation, purification, and modification.
For proteins that can be modified at the molecular level, we can use cysteine mutagenesis to introduce a single labeling site. For proteins that cannot be changed at the molecular level, we look for specific sites that can be modified using chemical methods (site-specific labeling). For protein that have no site-specific labeling sites, we use controlled labeling of surface amines plus advanced purification to obtain single ratio conjugates or near homogeneous multiple ratio conjugates.
Pipeline
In development
- CEACAM5 (XER-PDC-20-CEA)
(pancreatic, prostate, ovarian, glioblastoma, oesophageal cancer)
Following
4 different proteins with specific affinity to receptors overexpressed in selected tumor cells called:
- EphA2R (XER-PDC-20-EPH) (gastrointestinal, colorectal, pancreatic, lung, breast cancer). For the protein XER-PDC-20-EPH the following has been done:
- Design of the protein in silico
- Expression of the protein in mammalian cells.
- CD155 (XER-PDC-20-CD5) (gastrointestinal, colorectal, pancreatic, kidney cancer)
- CD133 (XER-PDC-20-CD3) (prostate, brain, liver, colorectal, lung, ovarian, breast, pancreatic, bone cancer)
- TEL-PDGFR (XER-PDC-20-TEL) (chronic myelomonocytic leukaemia)
A platform derived from the above-mentioned proteins that are bio-engineered and modified with a linker for further functionalization with the drugs of choice.
As backup in case one of the above proteins wouldn’t lead to the expected results, 18 high priority candidates have already been identified and recognized as interesting: TGFβR2; PTCH1; CD47; WNT; Hedgehog; ANXA2, P2X7, CD147, CD105, CD157, CD59, CLDN1-4, CD226, MIEN1, LAG3, CD44, CXCR6, CXCR4. A second group has been produced, is ready for further analysis and could also lead to interesting candidates, in this group we have: BCMA, CD22, CD123, CD30, CD38, CD33, CD10, CD16, CD4, IL-1-RAP, ITGB7, k-IgG, TRBC1, NKG2D, CD117, AXL, CD80, CD86, DR5, VEGFR2, cMet, IL13Ra2, EGFRvIII.