Biogen Collaborates with Sangamo Therapeutics for Gene- Regulation Therapies

Since 1869, when Swiss chemist Friedrich Miescher first identified DNA, and the subsequent discovery of the double helix1 by James Watson and Francis Crick, scientists have been working on advancing our understanding of the role genes play in determining how living organisms grow and develop. And as our understanding of genetics and genomics has continued to grow, the biotechnology industry is entering a new era, with the potential to revolutionize the way diseases are treated.

But how does this knowledge translate into tangible treatments that have the potential to benefit patients, especially in diseases that have seen slow progress in the form of meaningful treatments?

Biogen is collaborating with Sangamo Therapeutics to develop and commercialize gene-regulation therapies, starting with genes linked to Alzheimer’s disease, Parkinson’s disease, and an undisclosed neuromuscular disease, with the right to nominate up to nine more targets over a five-year period. Bringing together Sangamo’s genomic expertise and proprietary technology with Biogen’s proven track-record in developing and delivering treatments for neurological diseases, this collaboration is driven by a shared passion for science and a commitment to making a difference for patients.

 

Targeting Genes

Sangamo, headquartered in California, has developed a technology platform that allows scientists to control the expression of specific genes to achieve a desired therapeutic effect. The platform uses what’s called “zinc finger protein transcription factors” (ZFP-TFs) to repress or activate a targeted gene by binding to its unique DNA sequence. In pre-clinical studies, ZFP-TFs were delivered via one-time injection of an adeno-associated virus (AAV) vector.

Jeff Miller, senior director of innovation design and technology at Sangamo, looking at the structure of a zinc finger protein bound to DNA in 3D.  

In the case of Alzheimer’s disease, which is a type of tauopathy (a condition where tau protein accumulates in tangles in the brain), Biogen and Sangamo plan to use the platform to specifically research reduced expression of the gene responsible for making tau. For Parkinson’s, an alpha- synucleinopathy (one of a number of neurodegenerative disorders characterized by abnormal alpha-synuclein deposits), the two companies plan to use the technology to investigate the repression of the formation of that protein by zeroing in on its genetic code.

Jeff Miller, senior director of innovation design and technology at Sangamo, believes that the collaboration with Biogen could help his company as they work towards their goal of bringing the technology to market. Sangamo has demonstrated the efficacy of its gene-regulation platform in the laboratory through preclinical studies, he notes, but it needed a collaboration partner with deep clinical neurodegeneration expertise in order to work towards translating these successes to real human patients.

“My department at Sangamo is kind of the engine room; we deal with molecules and DNA and proteins,” Miller explains. “We know we can build these cutting-edge gene-regulation tools. But in order to achieve our goal of delivering them to patients with devastating neurological disorders, we wanted to collaborate with a partner who has the experience of taking that next step – the biological expertise, and clinical and commercial infrastructure.”

Jeff Miller, Senior Director of Innovation Design and Technology at Sangamo.

 

Real Potential for Real Patients

Bryan Zeitler, director of gene regulation at Sangamo, agrees that Biogen’s expertise and expansive neuroscience drug development capabilities complement Sangamo’s science. “We have extensive experience in the discovery and preclinical development of genomic medicines for neurological disease. Biogen is dedicated to neuroscience and has the resources and expertise to translate these investigational therapies to the clinic where they may impact patients’ lives in the future.”

As the research lead for Sangamo and Biogen’s ST-501 asset, a tau-targeted ZFP-TF program aiming to address the underlying genetic cause of tauopathies, Zeitler believes the technology is a “natural fit” for the problem they’re trying to solve. “Our genomes encode hundreds of zinc finger proteins that are expressed naturally in the brain,” he says. ST-501 and the ST-502 alpha-synuclein-targeted ZFP-TF won’t “edit” or introduce new genes to the human genome. “Rather than creating a double-stranded break like traditional gene editing, an engineered ZFP-TF has been shown to precisely tune down the expression of the genes that encode the aberrantly folded, neurotoxic proteins implicated in many neurodegenerative diseases.”

Zeitler recalls how, in his group’s earliest meetings with the Biogen team, it was clear to him that everyone who attended recognized the unique capabilities of ZFP-TFs to potentially address challenging neurological diseases. Also reassuring, he says, was the fact that, from the very start, everyone came prepared to share data and information. “You could imagine a very one-sided situation in a collaboration, especially when one collaboration partner is much bigger than the other. But that is not how it’s been at all. Instead, we’ve had this incredible spirit of real collaboration. Everything is transparent, science-driven and viewed as a joint effort.”

Early in the collaboration, Biogen conducted a commercial assessment for one of the Sangamo assets. Their technology obviously had value, Zeitler notes, but up to that point, their provisional product concept needed refinement.

 

“In a matter of weeks, the Biogen team had put together a presentation that demonstrated the possibilities and helped us come to a decision, focus on a path and move forward. It really helped to set the tone for everything that followed.”

Bryan Zeitler, Director of Gene Regulation at Sangamo

Looking ahead, as Sangamo continues to support the early research for these programs, Zeitler and Miller say that one of the next major goals for the collaboration is to transition the programs to Biogen to submit investigational new drug applications to the U.S. Food and Drug Administration (FDA). From there, if the FDA gives the go-ahead, Biogen would move on to clinical trials.

“I think we’ve come a long way at Sangamo, as has the entire field of genomic medicine,” Miller says. “It used to be that we were focused on the technical challenge of building a robust and reliable gene-regulation platform.” Although Sangamo scientists continue to work to further advance the field, the collaboration with Biogen brings an additional focus area. “Now we have the potential to develop innovative treatments to patients and bring hope to so many suffering from challenging neurological diseases.”