Firm is planning Phase II trial in patients with major depressive disorder.
U.K. CNS therapeutics firm Proximagen has sold its early clinical-stage sabcomeline program to BrainCells for up to $51 million in up-front and potential milestone payments. Proximagen acquired the muscarinic partial agonist in February through its buy-out of Minster Pharmaceuticals.
Under terms of the new sabcomeline deal BrainCells obtains worldwide rights to the drug and will be responsible for continued clinical development, regulatory filing, and commercialization. The firm will also have to honor any milestone and license payments due to GlaxoSmithKline as part of Minster’s 2001 sabcomeline licensing agreement with the firm. Proximagen says BrainCells plans to start a Phase II trial evaluating sabcomeline in combination with selective serotonin reuptake inhibitor therapy for the treatment of patients with major depressive disorder (MDD).
BrainCells is exploiting its neurogenesis platform to profile compounds and targets and compare them with both successful and failed CNS compounds. Focused primarily on the development of drugs for mood disorders, the firm maintains its technology has potential applications in other CNS fields including cognition, post-traumatic stress disorder, and brain repair.
The neurogenic platform comprises human neural stem cell and animal assays, which BrainCells uses to measure the proliferation, migration, differentiation, and survival of new neurons, combined with behavioral testing capabilities. The firm says marketed drugs used to treat different classes of CNS disorders such as depression, anxiety, psychoses, cognition, schizophrenia, and brain repair have very distinct mechanisms of action. The firm is using this differential data to select and reposition clinical-stage compounds with established safety databases, and to discover novel targets and compounds for the treatment of CNS disorders.
In June the firm reported data from an exploratory Phase II trial with lead compound BCI-540, which is in development for the treatment of MDD patients with anxiety who have previously failed an average of two antidepressants. Although the six-week study found no difference between the overall treatment group and placebo on scales for depression and anxiety, further analysis showed a positive efficacy signal in a subset of patients with MDD and general anxiety disorder, BrainCells claims. “BCI-540 began to separate from placebo by four weeks, which is in line with our understanding of how neurogenesis progresses in the brain,” commented Carrolee Barlow, M.D., Ph.D., CMO and CSO, when the data was reported. “It is an important clinical finding that we’ll take forward as we investigate the therapeutic opportunity of BCI-540 in this difficult-to-treat population.” BCI-540 is a bifunctional molecule designed to treat mood disorders both via AMPA potentiation and choline uptake enhancement.
The BrainCells pipeline also includes an antidepressant candidate, BCI-952, which comprises a fixed-dose combination of buspirone and melatonin. The firm says it has found that this combination demonstrates neurogenesis in vivo, together with evidence of activity in behavioral models of depression. Data from a Phase II investigator-initiated study with BCI-952 in MDD patients was reported in July 2009. The trial demonstrated that compared with placebo or bispirone alone, treatment using BCI-952 led to statistically significant improvements in mean Clinical Global Impression-Improvement scores and statistically significant improvements in secondary endpoints of IDSC30 and HAMA.
