Product pipeline

Project	Status	Therapeutic area
SER100	Clinical phase I completed	Isolated systolic hypertension
SER101	Clinical phase I completed	Congestive heart failure
SER102	Preclinical	Atrial fibrillation during intrathoracical surgery

SER100

SER100 is an opioid-1 (ORL1) agonist previously known as ZP120. SER100 was acquired from Zealand Pharma A/S in 2010. The results from previous studies in chronic and acute heart failure indicate that SER100 has a potential to treat isolated systolic hypertension (ISH), and indication which Serodus intends to pursue with a Clinical Phase IIA trial.

Patients with ISH are more likely to develop myocardial and vascular remodelling and arteriosclerosis, which predispose them to stroke, renal failure and myocardial infarction. Diabetes, chronic renal failure and obesity are other risk factors in patients with established ISH, and these patients have a significant higher incidence of congestive heart failure than those with only increased diastolic pressure.

SER101

SER101 is a selective 5-HT₄ receptor antagonist ready for clinical phase II for the treatment of congestive heart failure. SER101 is the code assigned to RO1160367, a compound which was licensed from Roche (see press release dated 9 December 2010).

In 2001 Prof. Levy and co-workers at the University of Oslo discovered that failing cardiac ventricles express functional 5-HT₄ receptors as a response to the malignant condition. This sensitization to serotonin signaling was believed to have a deteriorating effect on the disease. In analogy with the success of betablockers in heart failure it was hypothesized that a 5-HT₄ receptor antagonist could provide a similar benefit. After having confirmed the hypothesis in post-infarcted rats, a 6 months study of piboserod (GSK) in patients with congestive heart failure revealed that piboserod significantly improved left ventricular ejection fraction over placebo.

SER102

SER102 is developed by Serodus. It is a 5-HT₄ receptor antagonist. Serodus intends to develop SER102 for treatment of AF in patients undergoing intra-thoracical surgery. The compound has passed lead candidate selection and pre-clinical activities are about to be initiated.

The product candidate is a small molecule with low intestinal absorption. The compound can however be given parenterally and Serodus intends to develop a formulation for intravenous or subcutaneous treatment in patients developing AF during or 6 hours after intra-thoracical surgery. SER102 is expected to block the serotonin stimulation of the atria and consequently prevent AF or convert the AF to sinus rhythm.

Key references

1. Kjekshus J, et al. The Effect of Piboserod on Left Ventricular Function in Patients With Symptomatic Heart Failure.Eur J Heart Fail. 2009, 11(8), 771
2. Birkeland JA, et al. Effects of treatment with a 5-HT₄ receptor antagonist in heart failure. Br J Pharmacol. 2007 Jan;150(2):143-52. Epub 2006 Dec 11.
3. Qvigstad E, et al. Appearance of a ventricular 5-HT₄ receptor-mediated inotropic response to serotonin in heart failure. Cardiovasc Res. 2005 Mar 1;65(4):869-78.
4. Brattelid T, et al. Functional serotonin 5-HT₄ receptors in porcine and human ventricular myocardium with increased 5-HT₄ mRNA in heart failure. Naunyn-Schmiedeberg's Arch. Pharmacol., 370:157-166, 2004