Engineering the Future of Genetic Medicine

The 2020 Nobel Prize in Chemistry was awarded to Professors Jennifer Doudna and Emmanuelle Charpentier for their pioneering work developing CRISPR-Cas9 genome-editing technologies. A day later, the launch of Doudna's portfolio company Scribe Therapeutics, was announced.

The company's goal is to accelerate the development of "new era" CRISPR-based therapeutics in order to treat the underlying cause of diseases. This will be achieved through its "CRISPR by Design" platform that can engineer novel molecules designed for in vivo therapeutic use. Scribe's pipeline currently focuses on targeting genetically-driven forms of neurodegenerative diseases such as amyotrophic lateral sclerosis, or ALS.

Technology Networks recently interviewed Benjamin Oakes, co-founder, president and CEO at Scribe, to learn more about the company's next steps in "fulfilling the promise of CRISPR" and how it will navigate some of the challenges associated with developing CRISPR-based therapeutics, including efficacy, scale-up and high costs.

Molly Campbell (MC): For our readers that may be unfamiliar, please can you provide background context on Scribe's evolution thus far as a company?

Benjamin Oakes (BO): Scribe was founded to fulfil the promise of CRISPR – treating the underlying cause of disease within the human body. To do so, we have built – from the ground up – a fully integrated platform of CRISPR technologies around an engineering-first philosophy developed by my co-founders Brett Staahl, David Savage, Jennifer Doudna and me. In October 2020 we emerged from stealth with an initial $20 million Series A round of funding raised in 2018 and $400 million research collaboration with Biogen to develop therapies for ALS. We’re proud to announce today a $100 million Series B financing round from top tier investors to further advance our “CRISPR by Design” Platform and pipeline of in vivo therapies.

MC: What is Scribe's "CRISPR by Design" platform?

BO: “CRISPR by Design” is our unique molecular engineering approach for holistically redesigning the natural CRISPR molecules into best-in-class genetic medicine technologies. By honing enzymes such as CasX for greater efficacy, specificity and deliverability, we are able to create novel CRISPR technologies with the necessary therapeutic attributes needed to overcome the existing challenges of gene editing and delivery technologies. 

MC: Scribe's pipeline includes therapeutics for neurodegeneration and additional diseases. Please can you discuss these therapeutics in more detail and their current status in the preclinical/clinical testing?

BO: As part of our research collaboration with Biogen, we are currently developing CRISPR-based therapies that target a root cause of genetically-driven ALS. The program is the first application of our custom engineered technologies and our initial focus is on neurodegenerative disorders. Scribe is committed to addressing additional genetic diseases of significant unmet need, but at this time we are not disclosing further details of our pipeline.

MC: The funding announcement includes a statement that says, "By accelerating the shift from an artisanal discovery approach to a fully industrialized one, the company is poised to fundamentally transform how we treat and manage genetic diseases at scale". Please can you explore this statement in more detail? Can you talk about the issue of scale-up for therapies that target the genome? How is Scribe working to address this?

BO: Many of the therapies being developed and manufactured today are reliant on the discovery of new disease modifying biologics and small molecules that are the results of separate drug discovery campaigns aimed at specific therapeutic targets. This has resulted in high costs due to significant biology and technical risks. CRISPR promises a solution – the ability to directly edit disease-causing mutations at their source and thereby treat the root cause of a disease. As a result, novel CRISPR systems that can safely and effectively target any location in the genome could significantly improve and accelerate the drug development process.

MC: Gene therapies are notably more expensive than "traditional" therapeutics. How will Scribe work to ensure that the company's CRISPR-based therapies are accessible for the wider population? 

BO: We are dedicated to bringing CRISPR-based genetic medicines to the areas of greatest unmet need, including both rare and more prevalent diseases. Likewise, genetic medicine has the potential to change the economics of drug development and with that, lower the costs for all parties.

MC: Scribe was founded to address issues of safety, delivery, poor-editing outcomes and the uncertain IP landscape that currently limits CRISPR-based technologies. Can you expand on how Scribe will address such needs? 

BO: Our proprietary engineering platform is focused on continuing to create best-in-class tools to solve the technical and pragmatic challenges of genetic medicine such as delivery into the human body. We have precisely engineered non Cas9 enzymes that edit with high efficiency and specificity and can be delivered with a single AAV to enable effective in vivo applications of gene editing.

Benjamin Oakes was speaking to Molly Campbell, Science Writer for Technology Networks.