Prior to this synthetic route, bryostastin-1 had to be isolated from tons of natural sources to obtain grams of the drug.
Bryostatin-1 is a complex marine natural product with 11 chiral centers, which made the development of a synthetic method especially difficult. Animal studies have shown that bryostatin crosses the blood brain barrier.
Neurotrope has based its Phase 2a, expanded access program, and its ongoing Phase 2 Alzheimer's disease (AD) clinical trials, (top-line data anticipated to be announced in April, 2017), on extensive pre-clinical pharmacology and efficacy studies, led by Dr. Daniel Alkon, President and Chief Scientific Officer.
These animal studies have demonstrated bryostatin-1 efficacy for restorative synaptogenesis, prevention of neuronal death, and anti-amyloid, anti-tau metabolism via the activation of PKC epsilon pathways via bryostatin-1 activation.
The restorative therapeutic potential of bryostatin-1 and bryostatin- like activators, may be fundamental to a number of neuro-degenerative pathways and neurologic indications including AD, Fragile X syndrome (FXS), stroke, traumatic brain injury (TBI), and depression. Consequently, the need for an economical, commercial supply has increased.
Stanford University chemists, Drs. Paul Wender and Barry Trost, together with Dr. Garry Keck of the University of Utah, developed the initial routes to total synthesis of bryostatin-1.
The drug that Neurotrope has licensed has many potential benefits, including cost, time and manufacturing risk reduction.
Neurotrope CEO Dr. Susanne Wilke said: "Having access to a highly efficient synthesis of bryostatin-1 is taking the next step to making it commercially available.
Neurotrope president and chief scientific officer Dr. Alkon said: "We are delighted to further pursue this important synergy between world-class chemistry and what we believe to be pioneering basic and clinical neuroscience.
"Neurotrope can now plan for bryostatin-1 availability based upon the work of Dr. Wender, who has also developed a number of bryostatin derivatives called Bryologues that we have previously licensed."
Previously, bryostatin-1 was produced via a lengthy purification process. The National Cancer Institute (NCI) has, nevertheless, generously supplied bryostatin-1 for all of Neurotrope's clinical trials to date.
The NCI had extracted bryostatin-1 from Bugula Neritina, a sea sponge that houses the bacteria that excrete the natural product. From tons of the Bugula Neritina collected at that time, the NCI was able to extract 18 grams of bryostatin-1.
The NCI also initially investigated bryostatin-1 in a number of cancer indications, creating a large safety database for bryostatin-1 of over 1,500 patients who received the drug in those clinical trials.