Background:
We aim to unlock the therapeutic potential of 'undruggable' targets. Macrocyclic peptides are uniquely positioned to engage intracellular targets that are inaccessible to most biologics, and they also provide potential to address targets without a ligand-able pocket, which small molecule therapeutics require. Macrocyclic peptides represent a promising therapeutic modality due to their potential for high target specificity, increased stability and ability to modulate challenging biological targets. However, achieving oral bioavailability and/or sufficient cell permeability remains a key challenge in the development and deployment of macrocyclic peptides for clinical use.
Critical to the next wave of peptide innovation is a comprehensive understanding of the property space that governs oral absorption and cell permeability for macrocyclic peptides. Data-driven approaches, AI/ML augmentation, and high-throughput experimental platforms are central to our strategy to accelerate discovery and enhance our ability to design and deliver breakthrough peptide therapies.
To address this, AstraZeneca seeks to harness the power of Open Innovation by inviting collaborators from academia, biotech, and industry to share access to, or methodology for, in vitro assays at any stage of development that will help quantify physicochemical, permeability and stability properties of macrocyclic peptides. Leveraging AstraZeneca's expertise in molecular data analytics and AI, the collaborative team will use these methods to generate data against libraries of macrocyclic peptides. This will enable the collaborative team to build multiparameter AI/ML workflows to identify the most valuable screening cascade and enable robust prediction of the properties required for oral and cell-permeable macrocyclic peptides.
The Challenge:
AstraZeneca invites partners across the global scientific community to contribute established screening assays, or predictive models relevant to oral bioavailability and/or cell permeability of macrocyclic peptides that can help map and model the property space required for oral and cell-permeable macrocyclic peptides. We particularly welcome:
- High-throughput screening assays (in vitro and ex vivo) or advanced in silico platforms for quantifying key properties relevant to oral bioavailability and/or cellular permeability of macrocyclic peptides.
- Novel or proprietary methods for predicting, quantifying, or modelling the physicochemical space that governs permeability and oral absorption in macrocyclic peptides.
- Annotated data generated from these screening methods.
Proposed collaborations or data contributions should either provide experimental proof-of-concept, published evidence, or actionable approaches for generating datasets or screening tools that address these key parameters. Solutions that enable parallel evaluation of multiple macrocyclic peptides, or which deliver mechanistic or predictive insights into the determinants of oral and cell permeability, are particularly encouraged.
The Solution:
We are looking for collaborative solutions. To be considered for partnership or funding, proposals should demonstrate:
- Existing validated assays applicable to oral and cell-permeable macrocyclic peptide profiling in any stage of development (i.e. the research plan cannot be purely hypothetical in nature).
- A clear description of technology readiness or the immediate feasibility for screening, transfer or use by AstraZeneca or its partners.
- Evidence of relevance, such as proof-of-concept experiments, published data, prior deployment in peptide profiling or optimisation, or demonstrated utility in property mapping/predictive modelling.
- Potential for high throughput, reliability, reproducibility, and generation of FAIR data for scalable integration and validation within AstraZeneca developed AI/ML models. AstraZeneca can support data standardisation if needed.
- Description of supporting expertise, infrastructure, or computational resources enabling rapid onboarding or further development.
The selected collaborator will receive at least 8 benchmark compounds to confirm permeability ranking in a blinded study. Following screening, compounds will be unblinded for the collaborator and available to use freely.
Out of scope:
Proposals that are hypothetical, lack experimental feasibility, or involve low-throughput experimental or predictive modelling approaches that are not scalable for parallel evaluation of large compound sets will be given a lower priority.
Benefits of collaborators:
- Co-development opportunity with AstraZeneca
- Technology validation support: AstraZeneca's expertise in assay standardization and FAIR data principles to help optimize and validate your screening methods
- Co-publication opportunities: joint publication rights for significant findings and model developments arising
- Global network access: Introduction to AstraZeneca's broader peptide research network and potential additional collaboration opportunities
