Investing in Tome Biosciences

“That the powerful play goes on, and you may contribute a verse.”
      – Walt Whitman

Cures have long been medicine’s highest, and all-too elusive, aspiration. Therapies that compensate for or correct errors in DNA are the Holy Grail for devastating diseases caused by genetic mutations.

The first generation of genomic medicine, gene therapy, arrived in 1990 when doctors delivered a healthy gene to a girl with severe immunodeficiency so she could fight infections. Genomic medicine 2.0 dramatically kicked off with the discovery of CRISPR which, in just over a decade, has gone from gene-editing tool, to Nobel Prize, to FDA-approved medicine. Because CRISPR makes double-stranded breaks in DNA, with risks of unintended effects, early applications focused largely on inactivating disease genes. The development of more precise and versatile tools heralded the 3.0 era of genomic medicine: base editors change single “letters” of genetic code and prime editing enables small edits on the order of 50 letters.

MIT researchers Omar Abudayyeh and Jonathan Gootenberg trained under CRISPR pioneer Feng Zhang. I remember reading their PASTE paper and thinking it had the potential to be the fourth and final chapter in genomic medicine. PASTE enables programmable genomic integration (PGI)—the ability to insert any DNA sequence of any size precisely into any location without making double-stranded breaks.

Monogenic diseases are caused by an error or mutation in a specific gene; every patient with the disease has the same diseased gene but it’s not necessarily caused by the same mutation. Gene editors correct specific mutations; therapies based on this approach require one medicine per mutation, an unfeasible undertaking when there are many mutations across the population. By dropping in the entire fully corrected gene into the patient’s cells, PGI enables one medicine per gene irrespective of a patient’s specific mutation. This is a seismic shift. PGI is essentially molecular transplantation surgery, but for genes instead of organs.

In addition to correcting mutated genes inside the body, PGI has the potential to revolutionize engineering and design for cell therapies. Because of its ability to integrate large segments of DNA across multiple genomic locations in parallel, PGI brings rapid design-make-test timetables to cell therapy discovery, potentially broadening cell therapy applications well beyond cancer to other common diseases.

Seeing the profound potential for PGI, Jonthan and Omar founded Tome Biosciences—and this Tome is full of characters. CEO and diehard “Dead Poets Society” member Rahul Kakkar is a practicing physician and serial biotech entrepreneur coming off of the nearly $2 billion sale of his previous company. Chief Scientific Officer John Finn was an early employee at Intellia, leading their efforts to bring their CRISPR technology into the clinic. CTO Matt Barrows led the massive manufacturing scale-up for Moderna’s COVID vaccine. And COO Ed Freedman and Chief People Officer Diane Wong have decades of company-building experience. Together they have built a team at the frontier of genomic medicine.

Tome is launching with over $200 million to advance its PGI platform to focus on in vivo and ex vivo applications, with support from a16z Bio + Health, ARCH, GV, Longwood, Polaris and other leading investors. First up on Tome’s in vivo surgical slate: monogenic diseases of the liver. On the ex vivo cell engineering front, Tome is using PGI to rewire cells to cure common, chronic diseases—an area of great promise—with an initial focus on B-cell driven autoimmune diseases.

The story of genomic medicine is being written and Tome will contribute its verse.