Research Moves Forward
Notable among company presentations at “BPE” was Lentigen. The firm is developing a lentiviral vector drug delivery system, permitting the permanent introduction of genes into a wide range of both dividing and nondividing mammalian cells.
A safety switch can be introduced into the Lentigen system in the form of a gene that can be activated to allow the removal of the cells if needed. These features mean that the lentiviral system scores over more traditional vectors like plasmids or adeno-associated viral vectors, said Tim Ravenscroft, CEO.
Lentigen is using the technology in a range of applications involving gene delivery, to produce recombinant proteins, innovative vaccines, and in somatic and stem cell therapy. “Not many platforms can be applied in so many ways,” Ravenscroft added.
The company’s lead product is LG631, which protects stem cells from the toxic effects of temozolomide, the standard treatment for glioblastoma, and will shortly enter Phase I/II trials with Case Western University. Also in the pipeline is LG690 that delivers a safety gene that can switch off the graft-versus-host disease effects of allogeneic bone marrow transplants. Trials are planned with the National Cancer Institute and the Medical College of Wisconsin.
Meanwhile, funding from the Bill & Melinda Gates Foundation to the University of Wisconsin-Madison is allowing Lentigen to progress its plans for developing a new type of flu vaccine based on virus-like particles that could meet the urgent need for a more rapid response to seasonal and emerging viral strains.
Aquapharm Biodiscovery is a blue-biotech company based at the European Centre for Marine Biotechnology, where research is being conducted on novel chemistries found in the marine environment. The company has a particular interest in anti-infectives as well as antioxidants, biocatalysts, and anti-inflammatory compounds. It is pursuing a mixed business development model with both pharma and nonpharma interests.
Aquapharm is also looking at deep-sea and intertidal zones in areas such as Northern Europe, the Baltic sea, and the Arctic, searching through free-living microbes and symbionts. From a library of over 7,000 microbes, some which are previously uncharacterized and some which are completely new, it is getting a good hit rate, with plenty of compounds that have novel modes of action. Aquapharm has developed a fermentation technology that stresses microbes, encouraging the formation of interesting secondary metabolites. Recently, the company extended an existing R&D licence and signed a new commercial license with Dr. Reddy’s Laboratories.
Trophos has a cholesterol-oxime chemistry platform that reportedly delivers first-in-class compounds that can modulate dysfunctional mitochondria. The company has developed models involving live motor neurons, which are then physiologically stressed.
“Using this screening platform, we found that our compounds could protect cells from this stress,” explained Damian Marron, Ph.D., CEO. “We understand the structure-activity relationships, and we found that the oxime function and the cholesterol side chain are essential for activity. We believe that these compounds are unique in the way in which they interact with the proteins around the mitochondrial transition pore.”
TRO19622, the company’s lead product, has been shown to enhance motor neuron survival in preclinical models of motor neuron disease that the company has developed; it also has analgesic effects in peripheral neuropathy. Results of a Phase IIa proof of concept study of TRO19622 in diabetic neuropathy is expected soon, while a similar study in chemotherapy-related neuropathy is planned and another in non-alcoholic steatohepatitis is under way.
A Phase II/III registration trial of the compound in amyotrophic lateral sclerosis will begin soon and will proceed to Phase II in spinal muscular atrophy. “These are diseases that are hard to crack,” said Dr. Marron. “The focus on the mitochondria is a different approach that we believe can bring new hope.”
Finally, another compound, TRO40303, is in preclinical development for ischemia-reperfusion injury, a condition occurring after a heart attack and revascularization for which there is no approved treatment.