OSSIANIX USES SHARK-DERIVED ANTIBODIES TO CROSS THE BBB
OSSIANIX USES SHARK-DERIVED ANTIBODIES TO CROSS THE BBB
NeuroInsights 1st February 2016
Ossianix was founded in 2012 by Frank Walsh, Corey Goodman and Lynn Rutkowski, distinguished neuroscientists with extensive academic careers and senior level experience in the pharmaceutical industry. NeuroInsights caught up with Ossianix’s CEO Frank Walsh to discuss their innovative approach to crossing the blood-brain barrier.
During Walsh’s tenure at Wyeth, it became apparent to him that biological approaches to CNS diseases would represent the next-generation therapeutics. He became particularly interested in the first antibody molecule that appeared in evolution in fish, the single-domain variable regions of shark antibodies (VNRA). It is because of their small structure and its ability to bind different molecules, which Walsh and his team felt that it could address the problem that the BBB represents for delivery of therapeutics to the brain.
The team searched for strategies to deliver therapeutics to the brain and kept coming back to the transferrin receptor, a well-characterized receptor that delivers iron to the brain in the form of transferrin. Other groups had tried utilizing this receptor for similar purposes, but these groups used existing, off-the-shelf antibodies that were not designed to approach the BBB problem but were mostly anti-cancer agents. Walsh shares, “We felt this was a target worthy of studying. We used our in-house developed large phage-display libraries and we were able, via a screening approach, to come up with a family of binders to the transferrin receptor”.
The work to develop next-generation candidates added the features of cross-species binding and specificity to the transferrin receptor 1 (TFR1). The candidates then bind specifically the transferrin receptor, have a VNRA binding module and attached to it an antibody, can be delivered to the brain at therapeutic levels and be used in both rodents and humans. Walsh sums up “The ability to cross species, the fact that we have no effect on reticulocytes due to the specificity to the TFR1, and there is also no interaction with the transferrin binding site, has led a suite of binders that we are now using to target a variety of antibodies to the CNS. By making the antibodies bispecific, we can deliver therapeutic levels into the brain even with a single dose injection with a long-lasting effect up to 72 hours.” The results have been fruitful thus far and Ossianix has been able to show that using the targeting BACE1, they can get the antibody into the brain and reduce the levels of amyloid beta. They are now also looking into delivery of enzymes to treat lysosomal storage diseases and delivery of growth factors.
The company is pursuing their own targets and actively partnering with other companies. The two main internal projects are an anti-CD20 antibody for multiple sclerosis (MS) and CNS lymphoma, and a neurodegeneration project. The anti-CD20 antibody Rituxan has the ability to deplete B-cells. Ossianix has made Rituxan bispecific to deliver it to the brain for MS and CNS lymphoma. In MS, B-lymphocytes get into the brain and set up destructive ectopic B-cell follicles, leading to neurodegeneration. Walsh explains, “We believe that one of the causes for neurodegeneration is attack in the brain by B-lymphocytes, and there are no therapies that currently address this aspect of the disease.” The company has achieved proof-of-concept that they can deliver bispecific Rituxan to the brain and expect to have candidate in twelve months that can then be advanced to IND.
In their neurodegeneration project, Ossianix is targeting both amyloid beta and tau together at the same time. They have already made constructs and expect to have candidates in the next two years.
Ossianix is getting a lot of interest from the pharmaceutical industry. They have established a collaboration with Lundbeck focusing on two proprietary neurodegeneration targets and have delivered several versions of the antibodies for these targets, which are now in Lundbeck’s hands under in vivo investigations. Walsh shares, “We expect in 2016 to announce at least two deals with major pharmaceutical companies to deliver biological therapeutics to the brain.” The company also has an interest in orphan rare diseases, and Walsh indicates that is an area where they will most likely partner with other companies that are already pursuing therapies for these indications.
The company’s strategy over the next twelve months will be focused on establishing successful partnerships. At this time they are not planning to raise funds but this may change next year.
One of Ossianix’s strengths is their interaction with renowned academic institutions. Wash is a visiting professor at King’s College, and works closely with the university. They also collaborate with Royal Holloway University of London and with the University of Maryland. Walsh indicates that through these collaborations and with their stable financial position, they have the flexibility to move the company in different directions.
Walsh sees a bright future for neuropharma, “With a greater understand of disease mechanisms, the input from genome association studies, and other scientific developments, we will have a new set of therapeutics.” Ossianix is also developing VNARs to treat amyotrophic lateral sclerosis (ALS) with funding from The ALS Association, and Walsh is certain that these efforts will yield results. He closes saying, “There are some quick wins out there in the delivery of therapeutic biological to the CNS. We are set to accomplish this.”