CONFERENCE DAY TWO | THURSDAY APRIL 3, 2025

7:30 am Check In & Morning Coffee

8:20 am Chair’s Opening Remarks

Plotting the Course from Pipeline to Clinic to Inform Future Peptide Drug Discovery Efforts

8:30 am Invention of MK-0616 – Merck’s Macrocyclic Peptide Oral PCSK9 Inhibitor

  • Abbas Walji Senior Director, Discovery Chemistry, Merck

Synopsis

  • Highlighting the need for new modalities to drug challenging targets
  • Elevating cyclic peptides as privileged scaffolds and a potential alternative to small molecules and large biopharmaceuticals
  • Integrating various capabilities, including mRNA display and structure-based drug design, into drug discovery

9:00 am Turning Disordered Proteins “Druggable” with Intrametics TM

  • Laura Nevola Co-Founder, Chief Scientific Officer & Chief Operating Officer, IDP Pharma

Synopsis

  • Elevating that intrinsically disordered proteins (IDPs) represent half of the human proteins and perform a plethora of biological functions
  • Demonstrating how, IntrameticsTM , IDP Pharma’s proprietary technology, enables for the first-time the inhibition and cellular degradation of IDPs with peptidomimetics
  • Successfully delivering four peptide-derived drug candidates targeting novel IDP targets, with one at clinical stage

Combining Computational Approaches with Experimental Techniques to Investigate PeptideLigand Binding & Optimise for Solubility, Stability & Affinity

9:30 am Integrated Computational & Biochemical Cyclic Peptide Screening

Synopsis

  • Uncovering how passive permeability is achievable even for relatively large cyclic peptides
  • Understanding that consideration of PK from the start is critical
  • Careful integration of the best technologies available is required

10:00 am Biological Evaluation of Therapeutics Engineered with De Novo Designed Miniproteins

Synopsis

  • Engineering multivalent miniprotein immune cell engagers to design optimal immune synapses
  • Designing and validating biological strategies to assess ligand-receptor interactions with miniproteins
  • Evaluating pharmacokinetics parameters of miniprotein to engineer therapeutic products

10:30am Morning Refreshments, Networking Break & Scientific Poster Session

Weaving in Formulation Considerations to Inform Peptide Medicinal Chemistry Discovery, Design & Synthesis Requirements

11:30 am Delivering Orally Bioavailable Peptides with Increased Stability & Half-Life Through Formulation Innovation

Synopsis

  • Collaborating with formulation teams to learn how to optimize formulation for peptides of different sizes • Discussing biopharmaceutics mechanisms for different oral formulation platforms
  • Translating formulation considerations into early-stage design of peptides with clinical viability potential
  • Sharing key learnings from the successful launch of oral semaglutide and continued success of subcutaneous peptide products 

12:00 pm Realizing Needle-Free Protein Delivery: Formulation Strategies to Improve Stability & Efficacy

Synopsis

  • Carefully selecting excipients to secure a backbone for robust oral protein formulations
  • Addressing the multiple barriers impeding protein delivery through base formulations
  • Exploiting physiological metabolic pathways to be applied for a wide range of proteinbased drugs and vaccines

12:30pm Lunch & Networking Break

1:30 pm Highlighting Challenges in Oral Peptide Delivery & Defining Approaches to Overcome Them

Synopsis

  • Discussing limitations in oral peptide delivery and providing an overview of current advancements in the field
  • Overcoming the challenge of transitioning from a liquid to solid dosage formulation for new oral peptide delivery systems
  • Demonstrating species-related intestinal absorption and how we can ensure large animal to human translatability

2:00 pm Buccal Administration of Peptides: The EU BUCCAL-PEP Consortium

  • David J. Brayden Professor of Advanced Drug Delivery, University College Dublin

Synopsis

  • Exploring why buccal administration has some advantages over other routes
  • Designing buccal films to entrap peptides and permeation enhancers
  • Discovering a GLP-1 analogue candidate for prototype films

Highlighting Expanded Cutting-Edge Applications of Peptides as Drug Delivery Vehicles & Diagnostic Tools

2:30 pm Warburg for Warheads: Leveraging the Cybrexa Alphalex PDC for Antigen Agnostic Targeting of Tumor Cells

Synopsis

  • Introducing how to use pHLIP peptides for tumor targeting
  • Reviewing the discovery and development of tumor microenvironment sensitive anticancer PDCs
  • Optimizing the Alphalex-payload linker for delivering two different cytotoxic warhead classes

3:00pm Afternoon Networking Break

3:30 pm The Endosomal Escape Vehicle Platform Safely & Effectively Delivers Oligonucleotide Therapeutics to Skeletal and Cardiac Muscle Tissue for the Potential Treatment of Duchenne Muscular Dystrophy

  • Mah Kheirabadi Director - Discovery Chemistry, Entrada Therapeutics Inc.

Synopsis

  • Developing the Endosomal Escape Vehicle (EEV™) family of cyclic cell-penetrating peptides that were developed to overcome limitations of intracellular therapeutics
  • Delivering antisense oligonucleotides using EEV-PMO constructs to skeletal and cardiac muscle in preclinical models of Duchenne muscular dystrophy (DMD)
  • Discussing how healthy human volunteers were administered a single dose of ENTR601-44, a DMD exon 44 skipping EEV-PMO construct, and showed dose-dependent exon 44 skipping with no adverse events related to study drug
  • Demonstrating the therapeutic potential of the EEV platform and using findings to support further clinical development of EEV-PMO constructs in people living with DMD

4:00 pm Brain Delivery Using Peptide Shuttles: From Discovery to Application

Synopsis

  • Highlighting peptides as promising tools for drug delivery to the brain
  • Exploring potential applications delivering a broad range of cargoes in vitro and in vivo
  • Defining the relevant hallmarks of an ideal peptide shuttle

4:30 pm Discovery & Optimization of High-Affinity Macrocyclic Peptides for PET Imaging of Human Granzyme-B

Synopsis

  • Reviewing modality selection and the application of mRNA display screening to identify two high affinity hit classes of granzyme B binders
  • Characterizing lead candidates in a mouse xeno-graft versus host disease model and rhesus monkey distribution studies
  • Discussing prioritization, affinity optimization for a single hit class and identification of a preclinical candidate

5:00 pm Chair’s Closing Remarks & End of Summit