Chroma Medicine Nets $125 Million to Harness Nature’s Genomic Gatekeeper
Chroma CEO Dr. Catherine Stehman-Breen, M.D./Courtesy Chroma Medicine
There’s a new player on the epigenetic medicine block. Hailing from the gene-editing mecca of Massachusetts (aka Genetown), Chroma Medicine debuted Wednesday morning with $125 million in seed and Series A funding.
The seed financing was courtesy of Atlas Venture, Newpath Partners, and Sofinnova Partners, while Cormorant Asset Management led the Series A.
Epigenetic medicine, and epigenetic editing, in particular, is touted as an important next step in targeted gene therapy, in part because it harnesses nature’s innate mechanism for gene regulation.
“It leverages our own endogenous mechanism for regulating gene expression,” Dr. Catherine Stehman-Breen, M.D., Chroma’s chief executive officer, told BioSpace. “By leveraging that mechanism, it uses a highly evolved exquisite mechanism that was intended to regulate gene expression.”
Epigenetic editing allows scientists to modify individual chromatin marks at a defined region with exceptional specificity and efficiency. This makes it an attractive option for developing therapeutics that involve regulating gene expression.
Chroma President and Chief Scientific Officer Vic Myer, Ph.D., offered a hardware-software analogy.
“A cell has pre-programmed gene expression patterns, and essentially, the software that controls that is the epigenome. So, when it comes to therapeutic applications where the goal is to either turn a gene on or off that is in the patient’s genome already, we think epigenetic editing is the way to go because that’s how the cell would do it normally,” he explained. During early development, whole portions of the genome are shut off, while other whole portions are allowed to be expressed. “What we aspire to do is make a very small change in that epigenetic pattern at a very specific location to reprogram that piece of the genome to either be on or to be off.”
Chroma’s platform is based on the pioneering work of its six scientific founders: Luke Gilbert, Ph.D.; Keith Joung, M.D., Ph.D.; David Liu, Ph.D.; Angelo Lombardo, Ph.D.; Luigi Naldini, M.D., Ph.D.; and Jonathan Weissman, Ph.D.
In April 2021, Gilbert and Weissman published a paper in Cell about a new gene-editing technology called CRISPRoff that allows researchers to control gene expression with high specificity while leaving the DNA sequence unaltered. In 2016, Lombardo published his work on the inheritable silencing of endogenous genes by targeted epigenetic editing, also in Cell.
While remaining mum on pipeline specifics at this early stage, Stehman-Breen said Chroma has an opportunity to target a range of diseases that can be addressed by both in vivo and ex vivo approaches.
She shared that the platform possesses a breadth of options. “We can activate genes, we can silence genes, and we can multiplex—we can use a combination of activating and silencing,” she said, adding that this flexibility will allow Chroma to retune gene expression and address a range of diseases where multiple targets are in play.
“We’re really focused on rapidly progressing the technology to the clinic,” Myer shared. “As opposed to spending a lot of time doing target discovery or technology evaluation, we’re actually gearing up to push the technology towards the clinic and really build out the platform in the context of our lead therapeutic programs.”
He added that there is an important place for both gene editing and epigenetic editing in therapeutics.
“For a given application, say a classic recessive Mendelian disorder where both alleles are defective because they have a mutation, that’s a great place where a genome editor or base editor to go in and actually correct that mutation and change it back to the wild type function. That’s actually a place we won’t go.” However, they might mimic a protective allele or silence a toxic allele in a genetic disease where one allele is healthy and the other is not.
Myer indicated that the sweet spot for epigenetic editing, specifically multiplexing, is in complex therapies: “As we start thinking about really complicated treatments, and particularly in the cell therapy space, we think multiplexing is a place where the technology is really going to shine.”