Ensoma Inc., a gene therapy startup working to drastically simplify the production and delivery of genomic medicines, announced itself Feb. 11 with a $70 million series A financing plus a strategic collaboration with Takeda Pharmaceutical Co. Ltd., which licensed vectors from the company for up to five rare disease targets in a deal that could deliver as much as $1.25 billion in potential payouts. Ensoma's co-founder and seed investor, 5AM Ventures, led the financing. Takeda took a $10 million equity stake as part of the round.

"With this funding, we now have more than enough room for the next few years to bring our initial programs to first-in-human [trials] and a few more," the company’s executive chairman, Paula Soteropoulos, told BioWorld. Soteropoulos, former founding CEO of Akcea Therapeutics Inc., is a strategic advisor at 5AM. Kush Parmar, 5AM’s managing director, is Ensoma’s CEO.

Paula Soteropoulos, executive chairman, Ensoma

The Boston-based company has its sights set on creating in vivo gene therapies for both common and rare diseases, but will focus first on the latter, likely in a condition for which curative benefit has already been seen with ex vivo gene therapies. But programs in oncology, autoimmune and infectious disease could follow, Soteropoulos said.

Though generating a lot of interest from potential partners, she said Takeda was the right fit as the first, not only due to its rare disease focus but also its alignment with Ensoma’s team on their internal vision, which she described as “changing the game” in terms of market access to gene therapies and “making access equitable for all.”

“The Ensoma platform offers distinct advantages over AAV and ex vivo lentiviral gene therapy approaches with the potential to overcome some of the challenges associated with first-generation technologies,” said Madhu Natarajan, Takeda’s rare diseases drug discovery unit head.

Making big advances more accessible

Ensoma was founded about a year and a half ago to build on more than two decades of work by its scientific co-founders, gene editing pioneer Hans-Peter Kiem, of the Fred Hutchinson Cancer Research Center, and André Lieber, of the University of Washington School of Medicine. After working together for many years, they wanted to make big advances in genomic medicine more accessible to more people.

The product of their work, built on an exclusively licensed portfolio of technologies, is Ensoma's in vivo Engenious vectors, which are based on a helper dependent adenovirus. They're designed to be delivered via a single intravenous injection that can be done in a doctor's office. Testing in animal models, including nonhuman primates, has demonstrated an ability to deliver a variety of genome modification tools directly to hematopoietic stem cells or the cells that arise from them without the need for stem cell collection or prior myeloablative conditioning.

Ensoma's vectors have been specifically selected for very low seroprevalence, to avoid issues with immunogenicity, Soteropoulos said. Furthermore, they are engineered in such a way as to exclude viral DNA, leaving a lot of room to package whatever gene editing or integration tools are needed for disease modification, even multiple tools if a disease calls for it. "We have about five times the capacity of a lentiviral or AAV vector," Soteropoulos said, potentially giving the platform an ability to be used in treating a variety of diseases that others can't.

The Engenious vectors can also include regulatory elements specific to cell lineages, allowing for it to determine which type of cells its tools work on.

Manufacturing of the Engenious vector is more akin to small molecules than AAV or lentiviral vectors, which require large volumes of plasmids and other elements that Ensoma wouldn’t require, Soteropoulos said. Still, given the limited capacity of available gene therapy manufacturing facilities in the world, the company is already building its own GMP manufacturing capacity, with Daniel Leblanc, former head of manufacturing at Flexion Therapeutics Inc. Robert Peters, Ensoma’s chief scientific officer, most recently led the rare blood disorders research group at Sanofi SA.

In addition to 5AM Ventures, F-Prime Capital, Takeda Ventures, Viking Global Investors, Cormorant Capital, RIT Capital Partners, Alexandria Venture Investments and Symbiosis II LLC participated in the series A round. F-Prime’s president and managing partner, Stephen Knight, will join Ensoma’s board.