Investing in Scribe Therapeutics

“I watched a video by Bill Gates and Steve Wozniak from the beginning of the personal computer age 25 years ago. When they were asked when they realized the PC was going to take off, they said it was serendipitous, because society was at a point where people were ready and eager to adopt that technology. That’s a very interesting parallel to CRISPR…

Our own journey was going from the basic science from Emmanuelle through our realization that we had come across a pathway in bacteria that could be harnessed as a powerful genome engineering technique.”

— Prof. Jennifer Doudna, PhD., PLOS blogs, December 3, 2015.

The surge of advances that emerged from Bill Gates’ and Steve Wozniak’s respective companies are quintessential examples of the power of a tech approach. They put engineering at the center of innovation, with products improving following Moore’s Law, where a modest improvement year over year leads to exponential growth over decades. These immense advances are driven by the consistency of the iterative design process that defines the engineering approach.

How could one implement this tech approach in biology? The first step was genomics, which increased in power — uncovering the genetic underpinnings of many diseases — with a concomitant decrease in cost (a trend termed Flatley’s Law). But knowing the underlying genetic cause is only the beginning. What would a tech approach to treating diseases with a clear genetic origin look like?  

A natural place to turn is CRISPR. Even from its earliest days (as Prof. Doudna describes above), the promise of CRISPR-based therapeutics was clear — to take direct action on our knowledge of the genetic causes of disease by removing or replacing those errors, much like we would edit buggy code in a software program.  

The reality of gene editing via CRISPR is, however, incredibly complex. Nature did not evolve CRISPR for targeting the human genome — let alone as a precision gene editor — but rather (as George Church famously opined) as a form of “genetic vandalism” that bacteria use to defend against pathogens. And thus the CRISPR molecules discovered in nature suffer from many limitations for their use as human therapeutics, and — until now — there has not been a single set of tools that represents the ideal therapeutic genome editing modality. 

Scribe Therapeutics presents a solution unique amongst CRISPR companies to address these limitations: it was built from the ground up to take a tech approach. The founders set out with an intention to engineer the very best CRISPR platform, with a bold leap from CRISPR discovery to CRISPR design. Scribe moves beyond anything that could be found in nature to fully engineer novel molecules that expand and perfect on what evolution provides. Critical properties for therapeutic use, such as editing efficacy, specificity, delivery, targeting range, and immune system response are now directly engineered, with iterative improvements generation over generation, resulting in a single, integrated, molecular platform that overcomes each of these key limitations. This approach is already yielding immediate rewards, with the team meeting important milestones and demonstrating vast improvements in essential properties that will only continue to compound and grow. 

Not surprisingly, it takes a special team to accomplish these advances. Scribe was founded and is directed by CRISPR pioneers and expert molecular engineers, including CRISPR icon and co-discoverer Prof. Jennifer Doudna, PhD and her UC Berkeley collaborators Benjamin Oakes, PhD, Brett Staahl, PhD, and Prof. David Savage, PhD. Scribe started with foundational intellectual property (IP) and expertise derived from their work at UC Berkeley, including numerous distinct CRISPR molecules such as CasX and molecular engineering techniques that enable the holistic redesign of natural CRISPR enzymes. But these powerful foundations are only the beginning, serving as a starting point for engineering improved performance. Like Gates and Wozniac, the Scribe team has developed a technology at the exact moment when the demand for their solution is at a tipping point. Their next generation platform for CRISPR-based genetic medicine will fundamentally transform how we treat and manage disease at scale. 

I am thrilled that Andreessen Horowitz has led Scribe’s $20M Series A investment round and that I have joined their board of directors.Today I am excited to see Scribe unveil their mission and progress to the broader community. Scribe represents a major shift in therapeutics, from a discovery approach to a fully industrialized means to design treatments that address a large class of diseases — allowing for the rapid development of novel therapeutics to improve the lives of millions of people worldwide.   

The views expressed here are those of the individual AH Capital Management, L.L.C. (“a16z”) personnel quoted and are not the views of a16z or its affiliates. Certain information contained in here has been obtained from third-party sources, including from portfolio companies of funds managed by a16z. While taken from sources believed to be reliable, a16z has not independently verified such information and makes no representations about the enduring accuracy of the information or its appropriateness for a given situation. 

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