BioCrea Provides Update on Developmen?t Programmes for Partners

BioCrea GmbH, the first-in-class CNS drug discovery specialist, has provided an update on two unique proprietary small molecule programmes: Long-term acting GABAA positive allosteric modulators (LT GABAA PAMs) to treat epilepsy plus autism; and NMDA receptor 2B (NR2B) negative allosteric modulators (NAMs) to treat depression.

The pathways of both therapy approaches have been established in proof-of-concept trials conducted with similar compounds and they both show great potential to overcome limitations of their predecessors. BioCrea has initiated an outlicensing programme to expedite the progression of these assets into the clinic.

The LT GABAA PAMs programme provides innovative compounds for the acute and long-term treatment of a broad-range of seizure disorders. BioCrea's unique PAMs act on a GABAA modulatory site that is different from benzodiazepine or steroid binding sites of currently marketed drugs. The subtype selectivity of these LT GABAA b2-preferring PAMs offers excellent efficacy in multiple seizure disease models combined with a much improved safety profile compared to current treatment approaches.

BioCrea's compounds avoid common problems such as cognitive impairment, sedation, tolerance and dependency issues after multiple dosing. The mode of action for this class of compound also opens up the potential to work in combination with existing treatment approaches. BioCrea has developed multiple distinct chemical families with excellent developability profiles, good oral bioavailability, CNS penetration and in vivo activity. By the second half of 2014, BioCrea will have completed the LT GABAA PAM candidate selection.

In January 2014 the US Epilepsy Foundation granted its Epilepsy Innovation Seal of Excellence Award to BioCrea for the LT GABAA PAM programme.

The NR2B NAM programme is showing strong potential as a treatment for major depressive disorder (MDD), particularly for treatment resistant patients and patients with suicidal tendencies. By targeting the NMDA receptor subunit NR2B, BioCrea is developing a novel first-in-class programme to treat these diseases. NR2B NAM compounds overcome the limited effectiveness, late onset of action and side effects of available antidepressant medications.

Clinical studies with predecessor compounds have provided proof-of-concept for this target as a robust, rapid treatment of depression, especially in refractory patients. Studies also show that NR2B subtype-selective antagonists have superior tolerability when compared to non-selective agents like ketamine. BioCrea has addressed the NR2B target through two potent, distinct chemical families with a novel IP position. The compounds are efficacious in in vitro and in vivo assays, have an excellent side effect profile, blood-brain barrier penetration and developability parameters. This includes the potential for oral administration, which has been a difficulty in the development of NR2B selective agents in previous programmes.

BioCrea's NR2B NAM drug candidate will be ready for IND-enabling studies by year-end.

"First-in-class drug discovery based on a clinically validated mechanism of action is our contribution to enhance the probability of success in clinical trials. Both, the LT GABAA PAM and the NR2B NAM approaches have proven pathways through proof-of-concept trials," said Dr Tom Kronbach, CEO of BioCrea. "We are convinced our compounds with their unique efficacy, side effect profiles and developability parameters have the potential to provide much needed treatment options for refractory patients in a range of debilitating diseases. We are looking to complete our partnering activities to speed up development of these therapies for the benefit of doctors and patients."