In Seattle, Wash., the largest city in America’s Pacific Northwest and home to corporate giants in software and e-commerce, innovation must drip amidst all of the drops of rain that fall so predictably from its skies. Here Immusoft, a small gene therapy company, may be on the cusp of something that could one day have as much global impact as the offerings of its brand name neighbors.
If you haven’t heard of Immusoft yet, stay tuned. There’s a good chance you will. The company has big plans for B cell immunotherapy.
Founded in late 2009 by Matthew Scholz, a then- aspiring and now-bona fide biotech executive with a background in computer science, his idea for reprogramming the human immune system to fight disease early on caught the interest of major U.S. academic medical and research center partners and Silicon Valley notables like Peter Thiel.
Today, Scholz and Immusoft are quietly but inexorably moving ever closer to a human clinical proof of concept to harness the power of the bodies’ most powerful and durable secretory cell, a long-lived plasma cell as a novel and promising immunotherapy to enable sustained in vivo delivery of biologic drugs.
Immusoft’s proprietary platform for making this happen, Immune System Programming (ISP™) is the company’s secret sauce.
It is an ex vivo cell culture system that uses a non-viral vector — the Sleeping Beauty Transposon System — to genetically modify primary B cells, and differentiate them into plasmablasts and plasma cells. ISP has its origins in a B cell culture system invented by Noble laureate David Baltimore, Ph.D., in his Cal Tech lab. Scholz and Immusoft negotiated exclusive license to Baltimore’s technology and modified it extensively.
The company hopes that ISP cells may eventually replace the current Standard of Care for many conditions that require frequent needle injections with recombinant produced monoclonal antibodies, enzymes or other protein-based drugs.
ISP can be compared to chimeric antigen receptor T cell immunotherapies or CAR-T, which use viral or non-viral vectors to genetically modify T cells to seek and destroy tumor cells. But as an autologous cell therapy, ISP is more analogous to a traditional vaccine, which uses an antigen to stimulate the adaptive immune system to produce long-lived plasma cells, resulting in functional, long-term humoral immunity.
Immusoft’s research so far indicates that cells that are genetically modified by ISP will be long-lived and take up residence in survival niches where they can persist for decades. The half-life of a long-lived plasma cell is measured in years and decades.
If successful on a large scale and in humans, adoptive transfer and engraftment of ISP cells one day could become a reliable, ex vivo process to re-program long-term protein expression in the human body. It could become like an app store for the human body, one that would allow drug delivery for multiple indications.
It seems that ISP cells would offer the most clinical benefit to conditions that require a lifetime of enzyme or protein replacement therapy (lysosomal storage disorders or hemophilias), passive immunization with neutralizing antibodies (chronic HIV infection), or applications in regenerative medicine (sarcopenia or age-related muscle-wasting).
Compared to current gene therapy approaches using adeno-associated virus, it is not believed that ISP cells would elicit an immune response, so patients could be treated multiple times, even for multiple diseases, with the ISP platform.
Since demonstrating its own proof-of-concept for ISP in 2010, Immusoft has been hitting all the necessary business and clinical touch points.
It secured the necessary worldwide patents for its core technology early, and in 2016 acquired Discovery Genomics, Inc., which resulted in having a license to use the Sleeping Beauty Transposon System, an approach that is vastly more scalable and much less expensive than using a virus.
Immusoft has developed and maintained strategic alliances aimed at clinical translation of the ISP immunotherapy platform. In 2017, the company demonstrated clinical-grade manufacturing at human-scale with collaborators at the cGMP Cell Processing Facility at The Fred Hutchinson Cancer Research Center in Seattle, and began GLP toxicology studies with the goal of IND submission in early 2018.
For its clinical proof-of-concept, the company will collaborate with principal investigator Paul Orchard, M.D., Medical Director of the Inherited Metabolic & Storage Disease Bone Marrow Transplantation Program at the University of Minnesota in Minneapolis, Minn. This will be for Immusoft’s lead product, an ISP cell product to treat a rare pediatric lysosomal storage disorder, Mucopolysaccharidosis Type I (MPS I). The phase I investigator-sponsored trial will use expertise at the University of Minnesota’s Molecular Cellular Therapeutics group to collect patient samples, send and receive cellular material, and oversee the administration of the final product back into the patient.
In early January 2018, Immusoft closed a $3M initial tranche of a Series B financing. The full Series B is underway. The round is expected to provide Immusoft the funding it needs to complete its Phase I/II clinical trial in MPS-I and advance its pipeline.
Commensurate with this financing, biotechnology veteran Sean Ainsworth assumed the role of Immusoft CEO and Chairman of the Board. Ainsworth is affiliated with 600 Mile Challenge Fund, which led the Series B. Previously Ainsworth founded and led RetroSense Therapeutics, a gene therapy company he advanced into human clinical trials and sold to Allergan in 2016 in a deal valued at up to $555 million.
Immusoft has received support from prominent investors including Peter Thiel through FF Science, an early stage investment vehicle of Founders Fund, Tim Draper, Technium Partners, and others. Breakout Labs, a Thiel founded and led initiative supported Immusoft with one of its first grants in 2012. Among Immusoft’s other early grants was one from the U.S. National Institutes of Health.