Rare Daily Staff

Flagship Pioneering unveiled Laronde, a platform company developing a new engineered form of RNA that can be programmed to express therapeutic proteins inside the body, with a $50 million commitment to support its Endless RNA platform, or eRNA, and initial pipeline of new medicines.

“With Endless RNA we have created a new class of medicines that can be programmed to persistently express therapeutic proteins in the body, at tunable levels, without generating an unwanted immune response, in a continuously redosable manner, and with very simple delivery,” said Noubar Afeyan, founder and CEO of Flagship Pioneering, co-founder of Laronde and chairman of its Board of Directors. The possible applications of this platform are very broad, with applications that have the potential to replace or augment many drug modalities currently in use.”

The eRNA technology was invented at Flagship Labs by a team led by Flagship Pioneering General Partner, Avak Kahvejian, who was also the founding CEO of Laronde. The company began in 2017 as the 50th such life science platform developed within Flagship Labs and has since operated as part of the broader Flagship enterprise. In 2017, the team began to explore the therapeutic applicability of long non-coding RNA (lncRNA), naturally abundant in circular form within mammalian cells. Unlike natural messenger RNA (mRNA), which initiates translation by recruiting ribosomes through interaction with proteins bound to the mRNA’s 5′ region, natural circular lncRNA does not readily interact with ribosomes.

The Flagship team’s exploration led to the invention of eRNA, a proprietary, closed-loop RNA construct engineered to be translatable. Having no free ends, eRNA are not recognized by the innate immune system or exonuclease enzymes, and are highly stable, enabling a prolonged therapeutic effect. In addition, the therapeutic protein expression capabilities of eRNA are modular and programmable. Switching the eRNA “protein-coding cassette” directs the body to make different peptides, enzymes, antibodies, channels, and receptors, both inside and outside of the cell.

“eRNA therapeutics have the potential to be an essential and widespread class of medicines, expanding beyond small molecules and antibodies in their therapeutic applicability and utility,” said Kahvejian. “We can program eRNA medicines to code for a wide variety of therapeutic modalities. We asked ‘What if the circular nature of certain lncRNAs makes them ultra-stable in the body? Could we benefit from that stability to make a new class of therapeutic by making an RNA that has no free ends, but is translatable?’ These insights led to our inventing and optimizing eRNA, to demonstrate its ability to generate prolonged protein expression in vitro and eventually in vivo, and to establishing a strong foundational IP estate around this new class of medicine.”

To support the development and launch of multiple eRNA-based medicines, Laronde plans to build a modular and scalable eRNA Gigabase Factory to accommodate the clinical and commercial manufacture of up to 100 products and drug programs in the next 10 years. The company expects to hire more than 200 people over the next two years to support the advancement of its programs and platform.

“Because the programmable platform is so scalable, we have the potential to parallel process the development of multiple programs at the same time that, if successful, could help millions of people around the world,” said Diego Miralles, CEO of Laronde, and CEO-Partner at Flagship Pioneering.

Noubar Afeyan, founder and CEO of Flagship

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