Main Conference - Day 2 (May 13)Wednesday, 13 May 2026

This talk will introduce XtalPi's PepiX™, a leading AI peptide R&D platform. It integrates AI design, automated synthesis, and high-throughput screening, enabling efficient "design-synthesis-verification" cycles. PepiX™ unlocks the design and discovery of peptide drugs by vastly expanding chemical space searching via proprietary noncanonical amino acids. Case studies include a tumor vaccine candidate with strong preclinical results, solving challenges of an undruggable target, an oral weight-loss peptide development, and also efficient BBB penetration and delivery using peptides. PepiX™ sets a smart and efficient peptide R&D benchmark.

The explosion of chemical building-blocks for peptides creates a conundrum: from astronomical numbers of combinatorial possibilities, what sequences should we synthesize? This presentation covers the state-of-the-art computational pipeline for rational peptide design using the Rosetta software suite, as well as ongoing pipeline enhancements being implemented in the Masala software suite.

We introduce BoltzGen, an all-atom generative model for designing proteins and peptides across
all modalities to bind a wide range of biomolecular targets. We experimentally validate its capabilities in a total of eight diverse wetlab design campaigns with functional and affinity readouts across 26 targets.

I will present key multidisciplinary scientific milestones that have led to fifty years of melanocortin receptor (MCR) targeted peptide drug discovery as well as several recent FDA approvals. Knowledge of key MCR targets (e.g., MC1R, MC3R and MC4R) has significantly advanced in recent years in terms of structural biology and pharmacology. Likewise, the design of MCR targeted peptides having improved drug-like properties will advance the next generation of breakthrough medicines.

Oral peptide antagonists targeting the IL-23/IL-17 axis represent a promising new class for immune-mediated diseases. PN-881, a first-in-class and potential best-in-class oral IL-17 antagonist peptide, demonstrated potent and selective inhibition across IL-17AA, AF, and FF dimers. Preclinical studies demonstrate robust target engagement, excellent metabolic stability, and strong efficacy in inflammation models. These results highlight the potential of Protagonist Therapeutics’ peptide platform to deliver orally bioavailable, highly selective immune modulators and position PN-881 as a leading candidate in advancing peptide-based therapies for inflammatory diseases.

Helically constrained (Helicon) peptides enable the engagement, inhibition, and degradation of intracellular target proteins that are intractable to other therapeutic modalities. This talk will present the platforms that Parabilis has developed to explore the vast chemical space that Helicons can access, and will describe the hit discovery screen used to develop FOG-001, a clinically active β-catenin/TCF inhibitor that is currently in Phase 1/2 clinical trials.

Peptide radioconjugates are a relatively new generation of oncology treatment, combining small format tumour-targeting with precision delivery of radiation. Among the many advantages of peptide radioconjugates such as high target specificity, rapid clearance, modularity, minimal immunogenicity and ease of manufacture, there are numerous physiological challenges to overcome. Within this talk I would like to discuss emerging strategies to address such challenges arising during the development of peptide radioconjugates.

The presentation will discuss the discovery journey of ²²⁵Ac-ETN029, a macrocyclic peptide-based radioligand therapy intended for SCLC and other DLL3-expressing tumors. Structure-based drug design to enhance potency and optimize in vivo biodistribution will be discussed. Additionally, the efficacy study in DLL3-expressing xenograft models will be presented to highlight robust tumor regression. These studies support further investigation of the novel therapeutic ²²⁵Ac-ETN029 as a treatment for patients with DLL3-expressing solid tumors.