Introducing SB012 for the treatment of ulcerative colitis

Marburg, Germany, 29 April 2014

  • Phase IIa clinical trial of SB012 (the SECURE trial) approved by regulatory agencies

sterna biologicals GmbH & Co. KG ("sterna biologicals") announced today a significant expansion of the company's clinical development pipeline. In addition to SB010 for the treatment of Th2-driven asthma and SB011 for the treatment of atopic dermatitis, SB012 joins these two promising drug candidates as a further GATA-3 antagonist in a major chronic inflammatory indication.

sterna biologicals has worked closely with Prof Markus Neurath at the University of Erlangen to demonstrate pre-clinical proof-of-concept in state-of-the-art mouse models of inflammatory bowel disease. In these models, SB012 has shown efficacy comparable to treatment with anti TNFɑ monoclonal antibodies. In light of the excellent safety and efficacy data generated by SB010 in four completed clinical trials, sterna biologicals has decided to expedite the development of SB012 and move swiftly into the clinical.

The SECURE trial (SB012 for the treatment of active ulcerative colitis) has been approved by regulatory agencies and will commence in May 2014. The study – a randomised, double-blind, placebo-controlled Phase IIa clinical trial – will evaluate efficacy, pharmacokinetics, safety, and tolerability of SB012. 18 patients with moderate to severe active ulcerative colitis will be randomised 2:1 and will receive 28 days of SB012 or placebo treatment in addition to standard maintenance therapy. Primary endpoint is the improvement in Total Mayo Score, a well-established measure of disease severity comprising a range of endoscopic and clinical parameters.

The SECURE trial (SB012 for the treatment of active ulcerative colitis) has been approved by regulatory agencies and will commence in May 2014. The study – a randomised, double-blind, placebo-controlled Phase IIa clinical trial – will evaluate efficacy, pharmacokinetics, safety, and tolerability of SB012. 18 patients with moderate to severe active ulcerative colitis will be randomised 2:1 and will receive 28 days of SB012 or placebo treatment in addition to standard maintenance therapy. Primary endpoint is the improvement in Total Mayo Score, a well-established measure of disease severity comprising a range of endoscopic and clinical parameters.

About SB012
sterna biologicals' drug candidate SB012 is an enema-applied DNAzyme-based GATA-3 antagonist for the treatment of ulcerative colitis. The GATA-3-specific DNAzyme is also contained in the drug candidate SB010 for the treatment of Th2-driven asthma and SB011 for the treatment of atopic dermatitis. GATA-3 is the master transcription factor in regulating inflammatory diseases associated with the Th2 pathway such as ulcerative colitis. It is generally accepted that GATA-3 is necessary and sufficient for the production of key cytokines interleukin (IL)-4, IL- 5, and IL-13, which cause inflammation. In pre-clinical development, SB010 and SB012 significantly reduced expression of these cytokines and were safe and well-tolerated in toxicological studies with negligible side-effects. DNAzymes are single-stranded DNA molecules comprising a catalytic domain flanked by two binding domains. The binding domains attach to a specific sequence of targeted mRNA, in case of SB012 GATA-3 mRNA. After binding to the target, the catalytic domain then cleaves the mRNA, thereby inhibiting relevant cytokine expression.

About ulcerative colitis
Ulcerative colitis is characterised by a continuous mucosal inflammation which predominantly affects the large intestine. Clinical symptoms include persistent diarrhoea with severe faecal urgency and often incontinence, rectal bleeding, abdominal cramping, weight loss, and general malaise. It is estimated that the disease affects approximately 2 million people in the US, Europe, and Japan.