Peptide-based molecular degraders (PepTACs) offer a powerful strategy for targeted protein degradation by leveraging expanded binding interfaces and structure-guided design. However, their therapeutic translation remains limited by poor stability and inefficient cellular uptake. In this talk, I will present recent advances in enabling intracellular delivery of proteins and PepTACs using bioreversible anionic cloaking and amphiphilicity-driven loading into lipid-based carriers. These approaches enhance cytosolic access and functional activity, establishing generalisable design principles for overcoming delivery barriers and advancing targeted proteome modulation in cancer and other diseases.

Peptide ligands are increasingly used to direct diverse therapeutic modalities, such as radioligand therapies and oligonucleotide conjugates, to defined cell types and tissues. By exploiting precise, receptor-mediated binding, these targeting peptides can enhance on target delivery while reducing off target exposure. We will cover practical routes for discovery of peptide-targeting ligands, design principles, and strategies to improve stability, pharmacokinetics, and manufacturability in therapeutic applications.

Peptide-based nanocarriers offer unique opportunities for programmable self-assembly, yet rational design strategies that couple structural control with biological function remain limited. This talk will introduce fluorination as a quantitative molecular design parameter to program peptide self-assembly, morphology, and biological performance. More broadly, this talk will illustrate how precise control over side-chain chemistry can be leveraged to integrate structural programmability with functional delivery performance, opening new opportunities for the development of biodegradable, targeted drug delivery systems.

Cyclic hexapeptides represent a highly promising modality for targeting some of the most challenging interactions in drug discovery. Here, we present a suite of platforms for the generation of genetically encoded cyclic peptide libraries, both in living cells and within microfluidic droplets. These libraries are coupled to high-throughput functional assays, enabling the direct identification of inhibitors of protein–protein and protein–DNA interactions, including several first-in-class compounds. We further highlight examples where these hits have been successfully scaffold-hopped into small molecules, providing a foundation for the development of clinically relevant candidates.

VRG Therapeutics leverages its AI‑driven, end‑to‑end platform AI‑MPRO to develop novel miniprotein therapeutics to challenging targets such as ion channels and complex multi‑protein interfaces. AI-MPRO enables efficient progression from discovery to preclinical in vitro and in vivo proof‑of‑concept by integrating de novo protein design with rapid in silico–experimental iteration. This approach generates compact, highly optimized, first-in-class or best‑in‑class therapeutic candidates for targets traditionally considered intractable.

CFR2 receptor agonists have shown promise for the treatment of obesity and diabetes in pre-clinical studies. However, native urocortin-2, the ligand of CRF2, have a very short half-life and is not stable in formulation. Here, we will present the development of novel, long-acting and stable Urocortin-2 analogues. Obesity research is a hot topic where many pharmaceutical companies are heavily invested. CRF2 receptor agonists may provide a new approach to treat patients that works differently from GLP1 and amylin receptor agonists.

In this talk, I will introduce PepINVENT, a novel generative AI-based tool to address the challenges of scoring functions able to calculate properties of peptides with any type of amino acid and the retrosynthetic challenge of planning and evaluating the synthesis of ML suggested novel amino-acids.

Endotoxins - also called lipopolysaccharides (LPS) are directly involved in sepsis and toxic shock syndromes. Due to their omnipresence in the environment, endotoxins are common contaminants in the production of vaccines, injectable drugs and other pharmaceuticals. Endotoxins are highly resistant to heat- and chemical treatment, and current solutions have limitations. We have identified a synthetic peptide with an unprecedented affinity for LPS. The picomolar affinity will enable the development of endotoxin removal solutions, and potentially of clinical dialysis approaches.