Axial partners with great founders and inventors. We invest in early-stage life sciences companies such as Appia Bio, Seranova Bio, Delix Therapeutics, Simcha Therapeutics, among others often when they are no more than an idea. We are fanatical about helping the rare inventor who is compelled to build their own enduring business. If you or someone you know has a great idea or company in life sciences, Axial would be excited to get to know you and possibly invest in your vision and company . We are excited to be in business with you - email us at info@axialvc.com
Who leads Scribe?
Scribe Therapeutics was founded by Ben Oakes, Brett Staahl, Jennifer Doudna, and Dave Savage in 2018 to build a fully-integrated gene editing drug company. Oakes earned his PhD jointly in the Doudna and Savage Labs and went on to run his own lab at the Innovative Genomics Institute as a fellow. Staahl was a postdoc in the Doudna Lab. Jennifer Dounda helped invent the use of CRISPR as a gene editing tool while Dave Savage is a pioneer in synthetic biology and protein engineering (he’s also pretty good at basketball).
Scribe’s logo is pretty cool, inspired by Photo 51.
What does Scribe do?
Scribe is centered around a new CRISPR effector called CasX. The key advantage of the protein is that it is under 1000 amino acids (aa) making it ideal for delivery through a viral vector. Most Cas9 proteins are 1200-1400 aa and take around 4 kb of space. Most AAV vectors take up to 4.5 kb limiting the amount of guide and donor RNAs that can be co-delivered with a Cas9 protein. CasX would take around 3 kb of space opening more possibilities for delivery of CRISPR gene editing with an AAV. Scribe calls this technology their X-Editing platform.
Scribe uses this platform to develop new gene editing medicines focused on diseases that were traditionally limited by delivery. They are building a pipeline to bring CRISPR gene editing to neurodegenerative diseases; however, the core technology can be applied to any disease that has a genetic driver. Scribe is framing themselves as a gene editing and protein engineering company instead of one centered around CasX. The protein is an enabler for their business, but Scribe explicitly uses language to convey their ambitions to invent more and more CRISPR proteins. This quote really sums this up: “we are rapidly generating hundreds of synthetic CRISPR molecules and novel technologies every month and folding the best into a fully integrated set of genome editing modalities.”
What makes Scribe unique?
Ultimately, the CasX protein gives Scribe an incredible advantage right now. The ability to potentially deliver CRISPR gene editing with a single AAV vector opens a wide palette of diseases and tissues the technology can target. CRISPR medicines have been limited by delivery, and companies like Scribe and GenEdit are pioneering companies working to solve this bottleneck to begin addressing more indications.
The CasX paper was published in early 2019 and was a case study on how quickly the field of CRISPR protein discovery/characterization has come. Using metagenomic analysis on microbial DNA from groundwater samples (on a side point, Jill Banfield and her group should get more credit for the CRISPR revolution) the paper discovered a new Cas protein they called CasX (also known as Cas12e), which generates double-stranded breaks in DNA sequences complementary to its guide RNA. However, the CasX protein showed very little homology to Cas9 other than some overlap with the RuvC domain. As a result, the group used cryo-EM to generate 8 snapshots of CasX in various states; they only published the structures but could have put out a nice video on CasX’s movement. Due to its small size, CasX gives Scribe an entirely new gene editing platform for drug development.
Why I like what Scribe is doing?
Scribe actually has a pretty powerful platform technology. The simple power to package a CRISPR gene editing system in an AAV opens up so many more possibilities when compared to companies using Cas9 or other CRISPR effectors. Scribe focuses on 3 parts of its platform:
Greater activity (this is where CasX needs some major improvements)
Specificity
Deliverability (this is the key advantage)
This allowed the company to close out a pretty significant deal with Biogen on ALS out the gate. I am sure more deals are coming. Overall, Scribe is communicating their ambition to bring gene editing to a wide set of diseases and modalities:
Neurological Diseases
Ophthalmological Disease
Multisystem, Muscle & Metabolic
Hematopoietic Disorders
Cell Therapy
Congrats Ben, Brett, Dave, and Jennifer.
You can find Scribe here.