Metagenomi co-founder and CEO Brian C. Thomas, PhD

Metagenomi says the oversubscribed $175 million Series B financing it completed Tuesday will enable it to advance its lead in vivo and ex vivo gene editing therapy programs into the clinic.

The developer of CRISPR-based gene editing systems for developing cell and gene therapies also said the financing will allow it to expand its manufacturing, automation and artificial intelligence (AI) infrastructure, as well as further develop Metagenomi’s proprietary toolbox of next-generation gene editing systems.

Metagenomi asserts that its gene editing systems can edit DNA more accurately than current technologies, using a metagenomics-based discovery platform and analytical expertise that have revealed novel cellular machinery sourced from otherwise unknown organisms.

“We look forward to the next phase of the Company’s development as we accelerate our lead gene editing programs, and open new treatment options in metabolic, cardiovascular, and CNS diseases, as well as in immuno-oncology,” Metagenomi co-founder and CEO Brian C. Thomas, PhD, said in a statement. “Our expertise in mining the world’s natural environments for novel gene editing systems has resulted in the discovery of a powerful suite of gene editing tools.”

The company’s discovery engine is designed to work by recovering DNA from natural samples, then sequencing the naturally-derived genomes to discover novel gene editing tools, applying artificial intelligence (AI) to analyze and identify high-quality gene editing-based therapy candidates that are optimized for their therapeutic application. By adapting and integrating naturally evolved systems, Metagenomi says, its approach creates gene editing systems that are ultra-small, extremely efficient, highly specific, and carry a reduced immune response risk.

In vivo, cell therapy programs

Metagenomi’s pipeline consists of six in vivo programs and four cell therapy programs, all in preclinical phases. The in vivo programs focus on hemophilia A (lead optimization phase), four liver targets and cystic fibrosis using a CF Foundation grant (all in research phases).

The company’s cell therapy programs are all focused on immuno-oncology using four different approaches: T cell receptor (solid tumors) and chimeric antigen receptor T-cell (CAR-T; blood cancers), both in lead optimization phases; modular CAR (solid tumors) and induced pluripotent stem cell (iPSC platform for various tumors), both in research phases.

The financing propels Metagenomi to a total $300 million in capital raised since it was launched in 2018 by Thomas, a onetime researcher at University of California Berkeley, and the metagenomics researcher in whose lab he worked for 10 years, Jillian Banfield, FRS, FAA, still based at UC Berkeley and a scientific founder of the company.

A year earlier, Thomas, Banfield, and colleagues published a paper in Nature showing how they used genome-resolved metagenomics to identify a number of CRISPR–Cas systems, including what they said was, to their knowledge, the first reported Cas9 in the archaeal domain of life—a protein they found in little-studied nanoarchaea as part of an active CRISPR–Cas system. In bacteria, they discovered two previously unknown systems, CRISPR–CasX and CRISPR–CasY, among the most compact systems yet discovered to that point.

In a paper published in December 2020 in The CRISPR Journal, a peer-reviewed publication of GEN publisher Mary Ann Liebert, Inc., Thomas and seven Metagenomi colleagues led by corresponding author Christopher Brown identified novel families of Type V-A CRISPR nucleases through a large-scale analysis of metagenomes collected from a variety of complex environments. Seven novel nucleases showed in vitro activity with diverse protospacer adjacent motif (PAM) requirements, and ribonucleoprotein data showed editing efficiency >80% for therapeutically relevant targets in human cell lines.

Metagenomi emerged from stealth mode in November 2020 when it announced a $65 million Series A financing co-led by Humboldt Fund and Bayer’s investment arm Leaps by Bayer. Five months later, in April 2021, Metagenomi extended and closed the Series A at $75 million, as RA Capital Management joined the round’s investor syndicate.

“From the very beginning, we knew the Metagenomi Discovery Platform was going to be a unique and revolutionary technology development platform. We are proud to support the Company’s growth to further the development of new and transformative treatment options,” stated Sebastian Bernales, PhD, a Metagenomi co-founder and director who is General Partner of Humboldt Fund.

Moderna, Vertex Partnerships

In November, Metgenomi and Moderna launched a strategic research and development collaboration of undisclosed value, focused on advancing new gene editing systems for in vivo human therapeutic applications. The collaboration is designed to apply both Metagenomi’s  gene editing tools and Moderna’s mRNA platform and lipid nanoparticle (LNP) delivery technologies, with the goal of developing curative therapies for patients with unspecified “serious” genetic diseases addressing unmet medical needs.

Moderna agreed in return to pay Metagenomi upfront cash; fees tied to exercising options for targets of interest; payments tied to achieving development, regulatory, and commercial milestone payments; plus tiered royalties on net sales of any products commercialized by Moderna. Also, Moderna agreed to make an equity investment in Metagenomi in the form of a convertible note.

“This important collaboration represents another milestone on our journey to create transformational genome-engineering based medicines for patients,” Moderna CEO Stéphane Bancel wrote in the company’s 2021 Shareholder Letter.

Bancel said the Metagenomi collaboration was one of two partnerships through which the company’s Moderna Genomics unit aimed to expand the use of its platform to create more innovative drugs. The other is a three-year strategic research collaboration with Vertex Pharmaceuticals launched in September with the initial goal of discovering and optimizing novel lipid nanoparticles (LNPs) and mRNAs that can deliver gene-editing therapies to cells in the lungs.

“Our vision is to be a leader in large, complex genomic editing, and our strategy is to invest internally and to set up licensing agreements with next-generation gene editing companies,” Bancel added.

Moderna and Leaps by Bayer were among participants in the Series B financing, which was led by PFM Health Sciences, Farallon Capital Management, and an undisclosed “leading global investment firm.”

“Metagenomi’s method of discovering novel and versatile gene editing systems from nature is scientifically compelling and differentiated,” stated Santhosh Palani, PhD, an Investment Partner at PFM Health Sciences. “We are thrilled to be able to support Metagenomi as they advance their gene editing programs towards the clinic. Their gene editing systems hold the potential to have major benefits for patients.”

Additional new investors in the Series B included two biopharma giants, Bristol Myers Squibb and Novo Holdings A/S; as well as Eventide Asset Management, Deep Track Capital, Frazier Life Sciences, Pura Vida Investments, Irving Investors, Millennium Management, Surveyor Capital (a Citadel company), and Marshall Wace. They joined existing investors which included two that were named by Metagenomi, RA Capital Management, Humboldt Fund.

“We are honored to be supported by an impressive group of investors who understand the enormous potential of our gene editing capabilities,” Thomas added.

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