8:55 am Chair’s Opening Remarks
Peptide-Drug Conjugates for Challenging Targets in Advanced Cancer Therapies
9:00 am Exploring CBX-12-101: a First-in-Human Study of CBX-12, an AlphalexTM Peptide Drug Conjugate (PDC) in Patients With Advanced or Metastatic Solid Tumors
Synopsis
• AlphalexTM peptides undergo a conformational change in acidic environments facilitating targeted delivery of highly potent anti-cancer therapeutics
• Cybrexa PDCs do not require expression of any cell surface proteins
• Analyzing the activity seen with 3 different schedules in multiple tumor types
9:30 am Discovery & Optimization of Novel Cyclic Peptides for Precise Delivery of Pb-212-Based Targeted Alpha-Particle Therapy
Synopsis
• Pb-212 and Pb-203 theranostic radioisotopes
• Discovery and optimization of cyclic peptides for Pb-212 based radiopharmaceuticals
• Review key preclinical evaluation studies
10:00 am Bicycle Radionuclide Conjugates for precision targeting of solid tumors
Synopsis
- Bicycle® molecules are a novel peptide-based modality consisting of constrained peptides that form a bi-cyclic structure via ligation to a chemical scaffold and which are discovered using the Bicycle® phage display platform and have potential broad utility, allowing efficient and targeted delivery of different classes of payloads into tumors.
- We are developing Bicycle Radionuclide Conjugates (BRC™ molecules), in which Bicycle® molecules are employed as targeting vectors to deliver radioisotopes to tumors for cancer imaging and therapy.
- Bicycle® molecules exhibit properties that make them an ideal modality for radionuclide delivery. They can achieve exquisite binding specificity and high binding affinity and have demonstrated rapid tumor penetration, resulting in high accumulation of payload in the tumor but with limited exposure to normal tissues.
- We have used in vitro cell binding assays and mouse cell line derived xenograft models to characterize early MT1 targeted BRC™ molecules to establish binding properties and in vivo biodistribution and demonstrated that —BRC™ molecules can be chemically optimized to improve their in vivo biodistribution profiles.
10:30 am Morning Break & Networking
Evolving Peptide ADME Properties for Enhancing Their Therapeutic Success
11:30 am Optimizing Peptide Properties for Targeted Protein Degradation With High Specificity
Synopsis
• Reviewing next-generation designs for developing peptides as protein degraders
• Bridging the gap between glues and heterobifunctional degraders
• Addressing peptide-specific challenges within medicinal chemistry such as cell permeability and stability
12:00 pm Delving into 2-Pyridine Carboxaldehyde Derivatization for Cyclic Peptide Soft Spot ID & Improved Stability
Synopsis
• Utilization of N-terminal selectivity for simple identification of soft spots from in vitro matrices
• Tag optimization for increased sensitivity and longer simple N-terminal sequence tags
• Transfer to ex vivo matrices from PK screening
12:30 pm Lunch
Improving Peptide Oral Bioavailability to Open Up New Treatment Avenues
1:30 pm Leveraging Advances In Permeation Enhancers to Reach New Levels Of Bioavailability
Synopsis
• Maximizing bioavailability when combining permeation enhancers with a high-potency peptide
• Selecting the optimal permeation enhancer to use alongside a therapeutic peptide
• Highlighting the latest permeation enhancer updates and mechanisms
2:00 pm Leveraging Macrocyclic Peptides to Achieve Novel MOAs and High Specificity Against Intracellular Targets
Synopsis
- Extensive scaffold hopping and physicochemical property tuning of display technology hits.
- Generation of compounds with low and sub pM affinities and potent cell activity.
- Exploration of Unnatural Product’s parallel synthesis and computational design platform
Streamlining the Process of Moving Peptide Based Therapeutics Into The Clinic & Beyond
2:30 pm Photochemically-Enabled, Post-Translational Production of Therapeutic C-Terminal Amides”
Synopsis
- We have developed chemistry to convert recombinantly expressed peptides containing a C-terminal cysteine extension to a therapeutically relevant C-terminal amide via photochemical decomposition of the corresponding arylated cysteine thiol
- The process is robust, high-yielding, amenable to UV- or visible-light conditions, and is broadly applicable to all natural amino acid side chains at the C-terminus. We also demonstrate the applicability to a range of biologically relevant peptides
- Finally, we show that the photochemical process is amenable to flow-based methods at gram and decagram scale, indicating potential applicability to CMC processes alongside current methodologies dependent on resource intensive expression methods such as PAM enzyme