안녕하세요 보스턴 임박사입니다.

얼마전에 Epigenetic Editing을 위해 설립된 Epic Bio에 대해 글을 남긴 적이 있습니다. Stanford의 Stanley Qi교수팀의 연구를 바탕으로 설립된 회사라고 소개를 했었죠.

BIOTECH (72) – Epic Bio: Epigenetic Editing

이번에 소개할 Moonwalk Biosciences는 조금 다르게 보입니다. 첫번째 차이는 Co-founders 대부분이 AI/ML 전문가들입니다. GRAIL bio 출신들이죠.

Co-founders 중 한명이고 CEO인 Alex Aravanis는 2021년에 DNA methylation atlas 연구를 Nature에 이스라엘팀과 공동으로 보고한 적이 있습니다. 아마도 이런 Human Methylome Atlas를 Gene Editing과 융합시키는 것이 회사의 목표인 것 같습니다. 3년정도 후에 IND filing을 시리즈 B와 함께 하겠다는 계획을 봤을 때 아직 기술적으로 준비되어 있지 않은 것이 아닌가 하는 느낌이 납니다. 아마 조금 더 지켜보면 더 뉴스가 있겠죠. 너무 초기여서 아직 크게 말할 것은 없는 것 같습니다

그리고 Feng Zhang의 이름이 있기는 하지만 개념적인 설명일 뿐 아직 어떤 Editor를 쓰겠다는 것이나 어떤 Delivery system을 쓰겠다는 이야기가 없습니다. Feng Zhang교수가 최근에 창업한 VLP delivery platform company – Aera Therapeutics가 있기는 합니다만 이곳도 아직 초기단계이고 시작한지 얼마되지 않아 Layoff도 했습니다.

Biotech (32) – Aera Therapeutics

제가 보기에 Feng Zhang교수 단독으로 창업한 바이오텍이 임상까지 간 것이 있는지 모르겠습니다. 아직은 보지 못한 것 같습니다.

Moonwalk Biosciences Raises $57M to Edit the Epigenome – GEN Edge 1/4/2024

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.

Moonwalk steps out with $57m for epigenetic reprogramming platform – Longevity Technology 1/4/2024

Biotech co-founded by Alex Aravanis and Feng Zhang targets epigenetic code to reprogram cells to a healthy state.

Genomic medicine company Moonwalk Biosciences has emerged from stealth with $57 million in a combined seed and Series A financing to advance the development of precision epigenetic medicines. Co-founded by former Illumina CTO Dr Alex Aravanis and MIT and Harvard scientist Dr Feng Zhang, the company aims to reprogram cells to their healthy state, using “read-and-write” technologies to develop potentially curative therapies for diseases at the root cause level.

Moonwalk is targeting the epigenetic code – the “software of the genome” – the chemical changes that happen to our genes over time, but without fundamentally changing the DNA sequence itself. Changes to the epigenome are caused by our behavior and environment, and can affect the way our genes work.

Moonwalk says its platform provides a comprehensive view of the epigenome in both healthy and diseased states, combining AI prediction of methylation targets with a suite of epigenetic engineering tools.

Reprogramming the epigenome

Distinguishing itself from existing gene-editing methods, Moonwalk says its epigenetic editors use the cell’s natural regulation system to control multiple genes accurately and permanently in a single step, without altering the DNA sequence. The company claims this approach minimizes off-target effects and toxicities while maintaining the integrity of the primary DNA sequence – potentially enabling the creation of safer and more effective treatments for a range of diseases.

“While changes to the genome are irreversible, edits to the epigenome can be reprogrammed in different ways,” said Moonwalk CEO Aravanis, who co-authored a recent paper in Nature describing a DNA methylation atlas of human cells. “Epigenetic changes determine whether genes are turned on or off, and can potentially reverse disease, broadening the therapeutic landscape to find potential cures previously thought impossible.”

Potential in age-related disease

Cellular reprogramming is a hot topic in longevity, and Aravanis told us that Moonwalk is studying its effect on the epigenome.

“By converting transcription factor expression protocols into more precise epigenetic programs, it may be possible to achieve the benefits of programming or partial reprogramming, but with more specific control over cell state,” he said. “For example, to gain the benefits of higher function without losing the somatic features of cells.”

Aravanis added that combining Moonwalk’s “read” capability to fully characterize the methylation state at the single cell level with its “write” technology to change the methylation state, is “the ideal way to create the epigenetic version of reprogramming.”

When it comes to the company’s potential in targeting diseases of aging specifically, Aravanis told us that epigenetic alterations are “a hallmark of aging that strongly correlate with decline in cell function.”

“There is increasing evidence that these alterations are causally related to loss of function,” he said. “Moonwalk’s epigenome engineering platform can identify these epigenetics changes with unprecedented resolution, predict which targets may be causally related to the loss of function, and then reverse their methylation state, testing them as candidates to restore cell function.”

Funded through to IND studies

The new funding raised will support the ongoing development of Moonwalk’s epigenetic profiling and engineering technology platform, as well as the progression of its pipeline of epigenetic therapeutics towards clinical trials.

“The Series A will take the company toward IND enabling studies and filing,” Aravanis told us, explaining that the funding gives Moonwalk a cash runway of approximately three years, and that the company will work toward taking its development candidates into the clinic as part of a Series B financing.

Investors in the round include Alpha Wave Global, ARCH Venture Partners, Future Ventures, GV, Khosla Ventures, and YK Bioventures.

“Historically, the epigenome was poorly understood,” said Rick Gerson, Chairman of Alpha Wave Global. “Moonwalk is operating at a different level of biology, by profiling and unlocking our understanding of the epigenome to enable more precise engineering. The company’s novel platform technology provides the highest-resolution, complete view of the epigenome in health and disease to uniquely address unmet medical needs across various indications, including complex diseases.”