Marburg, Germany, 17 May 2015
- SB010 Phase IIa proof-of-concept results published in the New England Journal of Medicine
- SB010 Phase I programme results published in the Journal of Allergy and Clinical Immunology
- SB010 development programme comprising four completed clinical trials demonstrates excellent safety profile combined with efficacy comparable to monoclonal antibodies
sterna biologicals GmbH & Co. KG ("sterna biologicals") announced today that the full analysis of the recently completed Phase IIa proof-of-concept trial of SB010 was presented at the American Thoracic Society (ATS) 2015 International Conference in Denver, Colorado as part of session A2 entitled "The New England Journal of Medicine and JAMA. Discussion on the Edge: Reports of Recently Published Pulmonary Research." Concurrently, the paper was published in the New England Journal of Medicine (Krug et al., 2015).
SB010 is an inhaled first-in-class GATA-3 antagonist for the treatment of Th2-driven asthma. The drug selectively down regulates intracellular GATA-3 which orchestrates pro-inflammatory type 2 cytokines such as interleukin (IL)-4, IL-5, and IL-13 which cause key features of asthma.
In the randomised, double-blind, parallel group, multi-centre Phase IIa trial (NCT 01743768), SB010 treatment over 28 days significantly improved lung function after specific allergen challenge as compared to placebo. In the late phase asthmatic response, the primary end point of the trial, lung function improved by 35.1% (difference versus placebo, P=0.02) and in the early phase asthmatic response by 21.8% (difference versus placebo, P=0.03). The maximum decline in lung function was also improved, by 20.8% (difference versus placebo, P=0.09) in the late phase asthmatic response and by 17.9% (difference versus placebo, P=0.04) in the early phase asthmatic response. Mechanistic investigations comprising sputum eosinophils, sputum tryptase, and plasma IL-5 levels support the clinical effects.
SB010 was also safe and well tolerated. No serious treatment emergent adverse events occurred in both treatment groups and no noteworthy differences in treatment emergent adverse events were observed between study groups.
Professor Norbert Krug, principal investigator of the trial, commented: "Recent research indicates that approximately 50% of all asthmatics across all levels of disease severity can be considered Th2-driven based on their molecular endotype. Therefore, developing novel therapeutics specifically for this group of patients holds great promise, in particular via inhaled delivery. Further clinical trials with SB010 are warranted."
sterna biologicals also announced today that an overview of SB010's Phase I development programme was published in the Journal of Allergy and Clinical Immunology (Homburg et al., 2015). Over three Phase I trials, SB010 was safe and well-tolerated. Systemic exposure of the drug was consistently very low and no serious adverse events and off-target effects became apparent. No significant differences were observed in the total number of adverse events or proportion of subjects with adverse events between study groups in any of the trials.
Krug N, Hohlfeld J, Kirsten A, Kornmann O, Beeh K, Kappeler D, Korn S, Ignatenko S, Timmer W, Rogon C, Zeitvogel J, Nan Z, Bille J, Homburg U, Turowska A, Bachert C, Werfel T, Buhl R, Renz J, Garn H, Renz H. "Allergen-Induced Asthmatic Responses Modified by a GATA-3 Specific DNAzyme." NEJM. 2015 epub ahead of print.
Homburg U, Renz H, Timmer W, Hohlfeld J, Seitz F, Lüer K, Mayer A, Wacker A, Schmidt O, Kuhlmann J, Turowska A, Roller J, Kutz K, Schlüter G, Krug N, Garn H. "Letter to the Editor: Safety and Tolerability of a Novel Inhaled GATA3 mRNA Targeting DNAzyme in Patients with Th2-driven Asthma." JACI. 2015 epub ahead of print.
sterna biologicals' drug candidate SB010 is a first-in-class inhaled GATA-3 antagonist. GATA-3 is the master transcription factor in regulating Th2-driven inflammatory diseases such as asthma. 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 significantly reduced expression of these cytokines and was safe and well-tolerated in a comprehensive Phase I clinical programme. SB010 demonstrated strong clinical effects in a Phase IIa proof-of-concept trial. 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 SB010 GATA-3 mRNA. After binding to the target, the catalytic domain then cleaves the mRNA, thereby inhibiting relevant cytokine expression.
Asthma is a major chronic inflammatory disease of the airways affecting an estimated 300 million people worldwide. In OECD countries, prevalence is around 10% and increasing, with greater than average prevalence amongst women, children, and the elderly.