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Home » Rottapharm Biotech’s analgesic CR4056 meets the right OA phenotype

Rottapharm Biotech’s analgesic CR4056 meets the right OA phenotype

October 1, 2019          

Monza (Italy) – Rottapharm Biotech announces that results from the Phase 2 trial of CR4056 in chronic pain associated with osteoarthritis (OA) have been published online in Osteoarthritis and Cartilage, the leading journal in OA research. While providing the proof-of-concept that CR4056 is a novel non-opioid analgesic, the study involved an extensive phenotyping of participating patients with pain from knee OA. CR4056 performed particularly and significantly well in patients believed to belong to the metabolic OA phenotype.

“OA is a heterogeneous disease,” commented Lucio Rovati, Chief Scientific Officer at Rottapharm Biotech. “Our and other clinical scientists’ experience suggests that OA patients belong to different subsets corresponding to so-called disease phenotypes. The scientific community is working to clearly identify/diagnose these phenotypes, and to find molecular targets and biological pathways specific for them. It is indeed possible that a single magic bullet, suitable for all OA patients, does not exist and we will have to use drugs that are different for each phenotype.”
He then added: “Investigation into OA phenotypes is the approach we are following at Rottapharm Biotech. The metabolic OA phenotype is very common and occurs when there is a disruption of metabolic activities in the body, which may lead to obesity. CR4056 appears to be particularly effective on pain characterizing the metabolic OA phenotype: we want to pursue this specific signal in Phase 3 and we are discussing potential partnerships in this regard.”

CR4056 is a first-in-class imidazoline-2 (I2) receptor ligand (agonist profile) with potent analgesic activity in a broad spectrum of disease-based animal models of pain. In these experimental paradigms, CR4056 emerged as one of the most effective non-opioid analgesics ever described. Growing evidence on the functions of I2 receptors shows that I2 ligands facilitate the noradrenergic inhibitory (descending) pain pathways with an innovative, allosteric molecular mechanism.
CR4056 is a small molecule for oral administration. Potential therapeutic indications span from nociceptive to neuropathic pain.

The publication
“Efficacy and safety of the first-in-class imidazoline-2 receptor ligand CR4056 in pain from knee osteoarthritis and disease phenotypes: a randomized, double-blind, placebo-controlled phase 2 trial”, by Rovati LC, et al. Osteoarthritis Cartilage 2019.
The open access paper can be downloaded at the link in the reference above.

About Rottapharm Biotech

Rottapharm Biotech is an R&D company dedicated to innovative drug discovery and development. Rottapharm Biotech operates with a mixed discovery model that includes new chemical entities (small molecules) and a proprietary technology platform for the generation and selection of monoclonal antibodies. The R&D expertise embraces medicinal/computational chemistry, new target validation, pharmacological and pharmacokinetic characterization of new drug candidates, and design and conduct of innovative clinical trials. The company pipeline covers different therapeutic areas with focus on rheumatology (rheumatoid arthritis and osteoarthritis), pain and inflammation, immunomodulation and immuno-oncology, and selected oncology areas. The company strategy is to look for partnership at an early stage of development, ranging from preclinical significant stages to phase II proof-of-concept trials. For additional information about the company, please visit

Rottapharm Biotech contacts

Federica Girolami (Scientific Liaisons and Business Development Director)   Tel. +39 039 9066104

Rottapharm Biotech Srl, Via Valosa di Sopra 9, 20900 Monza (Italy)