It will be interesting to see where companies developing therapeutics based on epigenome editing technology choose to focus their development efforts over the next few years. For Moonwalk Biosciences CEO Alex Aravanis, MD, PhD, there are ample opportunities for epigenetic editing in cancer, neurodegenerative diseases, metabolic conditions, and much more. And, if all goes according to plan, he hopes Moonwalk will be able to file an investigational new drug application for its first therapeutic in two to three years.
Moonwalk, the most recent entrant to the epigenome editing market, is backed by Alpha Wave Ventures, ARCH Venture Partners, Future Ventures, GV, Khosla Ventures, and YK Bioventures. The company announced this week that it has raised $57 million in seed and Series A financing from these investors that will go toward developing its epigenetic profiling and engineering technology platform as well as progressing various epigenetic therapeutics toward the clinic.
The company has an impressive leadership team with deep expertise in areas such as epigenetic editing and clinical product development. In addition to Aravanis, Moonwalk’s co-founders include Arash Jamshidi, PhD, and Justin Valley, PhD, as well as scientific co-founder Feng Zhang, PhD, a core member at the Broad Institute, a professor of neuroscience at Massachusetts Institute of Technology, and an investigator at the Howard Hughes Medical Institute.
Since leaving his role as Illumina’s chief technology officer last year, Aravanis has spent the bulk of his time working on building Moonwalk. On the surface, moving into epigenome editing can seem like quite a drastic shift given his past roles at both Grail and Illumina.
But for Aravanis, it was an opportunity to bring his expertise in creating genomics-based tools to bear on a new challenge. “I spent the last 10 years of my career creating tools and diagnostics and assays and working with drug development companies to really take advantage of the power of the genome,” he told GEN. “I was excited about taking all of that background in technology development, diagnostics, clinical development, and applying it to an application that leverage[s] the ability to see complex biology.”
Moonwalk plans to develop a pipeline of treatments capable of using the cells’ natural regulation system to accurately and permanently control multiple genes in a single step without making changes to the primary DNA sequence. This is an important point and one that is highlighted by several companies that are trying to reprogram diseased cells by targeting the epigenetic code.
Activating or suppressing genes by methylating or demethylating particular targets rather than snipping and inserting DNA sidesteps some of the inherent risks of editing genes directly including potential structural changes or unintended insertions. An added benefit is the durability of epigenetic changes. The data suggests that modifications to methylation do stay in place and those changes are successfully transmitted to daughter cells even after multiple cell divisions. However the effectiveness of epigenomic editing remains to be seen.
“There’s been a lot of evidence mounting over the years about the importance of the epigenome in health and disease. And also obviously cells change a lot as we age and as they develop pathologies. And that’s reflected in the epigenome,” Aravanis said. “It’s a very appealing concept to be able to kind of see root level changes in the epigenome and then have a technology to modify it and then develop therapeutics based on that.”
Moonwalk claims to be the first company to couple an epigenetic discovery platform with precise engineering. Its proprietary technology has two key components. A so-called read component is designed to capture methylation information from the entire genome—about 28 million sites. It gives the company insights into the methylation present in both healthy and diseased states, allowing it to make predictions about complex methylation patterns as well as identify which are the best targets to hit.
The rubber meets the road in the second component of the company’s platform. This is where the company uses editing technology designed by Zhang, the company’s scientific co-founder, to modify methylation states in the genome. In addition to his work on CRISPR, Zhang is perhaps “one of the earliest inventors of this concept of modifying the epigenome directly,” Aravanis noted, making him a natural fit for the company.
At this time, Moonwalk is keeping the exact details of its therapeutic pipeline close to its chest; however, Aravanis did say that the goal is to target areas of major unmet need that are tractable from a clinical development standpoint. “We have more work to do over this year to understand where the technology can make the biggest impact initially,” he said. “What’s exciting is that the epigenome and epigenetic changes are relevant in pretty much any disease. So there’s lots of targets and, and lots of indications … but we need to be very thoughtful about what are the first ones that we really want to focus on.”
Moonwalk is not the only company that has taken notice of the epigenome’s potential nor is it the only one with a business model centered on developing and commercializing therapeutics.
The shortlist includes Chroma Medicine and Tune Therapeutics both of whom are betting big on epigenome editing-based therapeutics. Last March, Chroma completed a $135 million Series B financing that it planned to use to continue building its platform for epigenetically altering gene expression. Tune, which opened its doors in 2021, has already made clear what at least one of its target areas would be. The company announced late last year that it is working on an approach for treating chronic hepatitis B virus infections based on its proprietary epigenome editing technology. It hopes to have TUNE-401 in the clinic by the end of this year.
Aravanis acknowledged the other players while highlighting what he believes sets Moonwalk apart. Most notably its ability to comprehensively characterize all of the methylation states in the genome, to understand the effects of epigenetic editing and how best to make modifications, and also the ability to make predictions about complex methylation patterns. The companies could also differ in terms of the disease areas they choose to target with their respective platforms.