Federica Tucci
Principal Research Scientist
IRBM
Talk Information
Peptide Therapeutics from Discovery to the Clinic
17 June 2025, 11:20am - 11:35am, in the Pacific Jewel Ballroom
L31 – R2R01, a Potent Long-Acting RXFP1 Peptide Agonist as Clinical Candidate in Phase 2 Studies for Cardiovascular and Renal Diseases
Dr. Federica Tucci is a Principal Research Scientist in Peptide Chemistry at IRBM S.p.A. in Pomezia, Italy. She specializes in the design and optimization of therapeutic peptides, with a focus on cardiovascular and renal diseases.
Education
Dr. Tucci earned her degree in Chemistry from the Università della Calabria. She furthered her studies in Chemical Biology at Cardiff University, enhancing her expertise in peptide science and medicinal chemistry.
Professional Experience
At IRBM, Dr. Tucci plays a pivotal role in the Peptides and Small Molecules R&D Department. Her work involves the development of peptide-based therapeutics, contributing to the advancement of novel treatment options for various diseases.
Research Contributions
Dr. Tucci's research focuses on the development of long-acting peptide agonists targeting the relaxin family peptide receptor 1 (RXFP1). Notably, she contributed to the identification of R2R01, a potent RXFP1 agonist with potential applications in treating cardiovascular and renal conditions.
Notable Publications
Dr. Tucci has co-authored several peer-reviewed articles in esteemed journals, including the Journal of Medicinal Chemistry. Her publications detail the design and pharmacological evaluation of peptide therapeutics, underscoring her contributions to medicinal chemistry.
R2R01, a Potent Long-Acting RXFP1 Peptide Agonist as Clinical Candidate in Phase 2 Studies for Cardiovascular and Renal Diseases
IRBM, aPeptide Chemistry, bTranslational Biology cExperimental Pharmacology, Pomezia, Italy; Sanofi R&D, dIntegrated Drug Discovery, eCardio-Vascular and Metabolism, fDMPK, Investigative Toxicology Pre Clinical Safety Franceg Chilly Mazarin 91385 and Vitry sur Seine 94400, France
A C18 fatty acid single-chain analog based on the chain B of the relaxin-2 peptide hormone was recently identified as a potent, selective RXFP1 agonist with extended duration pharmacokinetics (PK)1,2. Advanced PK profiling of this compound highlighted elevated levels of oxidative metabolism occurring in dogs and minipigs, which precluded further development3. Extensive optimization efforts to overcome these issues led to the design of new analogs with increased stability against metabolic oxidation while maintaining sub-nanomolar RXFP1 activity.
Key structural elements, including fatty acid chain length, attachment position, and linker structure were modified to improve PK parameters. Additionally, incorporation of α-methyl-Lys at position 30, together with other modifications, resulted in sub-nanomolar potency on RXFP1, improved duration of action, and reduced pseudo-allergic reactions due to mast cell activation4.
Our studies demonstrate that an integrated platform employing a combination of in vitro and in vivo approaches is needed for the development of peptide therapeutics and the identification of clinical candidates with improved probability of success. The R2R01 peptide from this series is undergoing Phase 2 clinical studies in heart failure and hepatorenal syndrome5.
1. Mallart S. J. Med. Chem. 2021, 64(4):2139–2150.
2. Illiano S. Sci. Rep. 2022, 12(1):20435.
3. Esposito S. J. Pharm. Biomed. Anal. 2023, 227, 115256.
4. Mallart S. J. Med. Chem. 2025, in press.
5. Poirier B. Br. J. Pharmacol. 2024.