CRISPR gene editing technology is one of the most cutting-edge technologies in the biopharmaceutical field, and recent regulatory approvals have demonstrated the tremendous progress it has made in a relatively short period of time.

Devyn Smith, CEO, Arbor Biotechnologies
Devyn Smith, CEO of Arbor Biotechnologies
Image courtesy of Arbor Biotechnologies
 

Arbor Biotechnologies is preparing for the next phase of the gene editing revolution by developing tools that can shape and optimize existing strategies, aiming to cover more disease targets. This preclinical-stage company, co-founded by CRISPR pioneer Zhang Feng and Illumina founder David Walt, is currently focused on liver and central nervous system diseases.

CRISPR is used to modify DNA, typically in conjunction with the Cas9 protein, to locate the correct site on a gene. Arbor, however, hopes to expand this toolbox by adding more proteins to target different genes, thereby developing treatments for more diseases. Its lead program targets hyperoxaluria, which, according to CEO Devyn Smith, is close to submitting an Investigational New Drug (IND) application next year. The company's early pipeline also involves amyotrophic lateral sclerosis (ALS), with plans to submit three applications within the next three years.

"Gene editing at some point will be able to do things that no other therapeutic modality can do," said Smith. "In simple genetic diseases, there are mutations in genes that need to be corrected; and as our understanding of disease biology deepens, we need to think more precisely about other factors."

"In the long term, I hope that one day gene editing will become part of our worldview."

—Devyn Smith, CEO of Arbor Biotechnologies

In addition to developing its own therapies, Arbor has established a partnership with Vertex Pharmaceuticals—which, together with CRISPR Therapeutics, drove the FDA's first approval of a gene editing therapy this month—aimed at providing more precise gene editing tools.

Here, Smith discusses what makes Arbor unique in the CRISPR field and the evolution of the field.

This interview has been edited for length and style.

PHARMAVOICE: Please tell us about Arbor's origins and what makes it unique in the field of gene editing.

DEVYN SMITH:The key difference between Arbor and many other companies is that Arbor was founded on a concept rather than intellectual property—at the time, everyone was using Cas9, but it was clear that other approaches needed to be identified to provide more functionality and greater disease treatment capabilities. That was the founding principle of the company, and since then, it has built a deep discovery tool engine that allows us to discover novel editing approaches. We have leveraged the large number of nucleases we discovered to build a technology platform that covers all needs for DNA editing.

For small molecule drugs, screening antibodies requires a library of six million molecules. Gene editing, while not requiring six million tools, does require enough tools to cover a broad set of targets. Another important aspect is ensuring we can quickly translate these discoveries into therapies, so we place great emphasis on what we call a 'portal indication strategy'—choosing one indication and going deep early. Our focus is on central nervous system and liver diseases.

CRISPR technology has cleared regulatory hurdles in the past few months. What does this mean for you and the future of the field?

What surprises me is that it took only 10 years from the original paper from Zhang Feng's lab to an approved product—that's very fast. It will greatly improve patients' lives and also paves the way for these new methods of editing DNA. From Arbor's perspective, we celebrate this. There is still work to be done when moving to in vivo approaches. We believe Cas9 is powerful and widely used, but it has limitations and can only do so much. Therefore, there is an opportunity to introduce a range of tools to expand capabilities. We are encouraged by the CRISPR approval and hope it will be the vanguard for more approvals in the field.

As these new tools enter the market, how do you see Arbor's long-term development?

In the ex vivo field, we don't do executable cell therapies—instead, we partner with collaborators to provide the tools they need. In the in vivo field, we focus on developing our own therapies for liver and central nervous system diseases, starting with ALS. Our goal is to submit three applications within the next three years, and the key lies in the breadth of our toolbox. Ensuring we have the right technologies and tools, as well as a team of dedicated, knowledgeable drug developers. By focusing on a single portal indication, we can achieve success there and then expand to other indications. We are very disciplined in our pipeline planning, not trying to do too much, but learning to walk before we run.

Why liver and central nervous system? How did you decide on these initial targets?

We wanted to find areas where the delivery route is clear and where we could be the first editors to enter that disease. In the liver, we ensure we can differentiate and do things others cannot. The central nervous system is different; the industry has struggled to crack it for years because the biology is not yet fully understood. Now, we are beginning to understand the potential genetic contributions to disease pathology, and there are a large number of open genetic targets available for gene editing. There is a real opportunity there, and the potential could be life-changing.

As gene editing technology advances, what major shifts do you see?

In the short term, I think we will see more clinical data from in vivo therapies emerge. Currently, only a few companies have entered the clinic, but others will follow. We are beginning to understand the current capabilities of the technology and hope to see one-time solutions for patients.

In the medium term, you will see a shift from gene knockdown approaches to more sophisticated editing, such as rewriting and inserting larger DNA fragments to achieve more precise outcomes.

In the long term, I hope that one day gene editing will become part of our worldview. You go to the doctor, your DNA is sequenced, and they identify 10 issues that need to be fixed to prevent potential diseases. It's a bit like vaccines. When that time comes, perhaps for my great-grandchildren, the world will be vastly different—not treating ALS after it occurs, but preventing it from the start. It will be a long road, but for me, this is exciting and revolutionary for healthcare.