Dipeptidyl peptidase I (cathepsin C)

- a novel target for the treatment of inflammatory diseases

 

UNIZYME Laboratories is a virtual Danish biotech company focused on design and development of novel small molecule inhibitors of dipeptidyl peptidase I (DPPI; also known as cathepsin C) for treatment of inflammatory diseases.

 

DPPI is an activator of pro-inflammatory proteases and a drug target for a number of chronic diseases with components of neutrophil inflammation, such as COPD, cystic fibrosis, alpha-1 antitrypsin deficiency, rheumatoid arthritis and gout.

 

DPPI removes N-terminal dipeptides and thereby activates a number of “inflammatory” serine proteases known to be involved in a vast variety of inflammatory conditions. These proteases encompass neutrophil elastase, proteinase 3, and cathepsin G.

 

 

The proteases are synthesized and activated by DPPI in the bone marrow. Inhibitors of DPPI reduce levels of inflammatory proteases and are likely to be useful for treatment of protease-driven inflammatory diseases.

 

Unizyme has developed an oral available candidate drug XPZ-35, which has a PK profile that supports a once-daily oral dosing regime. The next step in the XPZ-35 development process is GMP batch production and two species tox analysis prior to entering phase 1 clinical testing. IPR for XPZ-35 and the backup program has priority date September 2013.

 

Unizyme has demonstrated significant effect in the collagen antibody-induced arthritis (CAIA) mouse model for rheumatoid arthritis with the DPPI inhibitor tool compound XPZ-01. There is also compelling data that supports DPPI as an attractive drug target in chronic lung diseases with components of neutrophil inflammation – examples are:

  • The DPPI inhibitor tool compound MOTP, prevents the development of emphysema following 32 weeks smoke exposure in a COPD animal model
  • Lack of elastase reduces inflammation, mucus hypersecretion, and emphysema in mice with cystic fibrosis-like lung disease 
  • Clinical stable patients with either alpha-1 antitrypsin deficiency or usual COPD with chronic bronchitis has elevated Pr3 activity in sputum and Pr3 activity is greater during exacerbations than in stable state
 

Unizyme  is now in a process of identifying a partner/licensee or investors that can bring XPZ-35 into clinical development for proof-of-concept in selected disease(s). Contact: John Pedersen.

 

June 2014