Codiak gets a competitor, as Mantra Bio leaves stealth and enters growing exosome space
Alex Mok had been trying to build mini-organs in a lab for years, when he started reading about research into a form of cellular postal service called exosomes.
Scientists were beginning to see how these minute envelopes carried messages between cells, helping them form tissue or, when things go wrong, cause disease. Mok started immersing himself into the field too late to change the company, called CellASIC, which he co-founded after leaving UC Berkeley. It was still good enough to sell it to Merck KgAA, but he began wondering about the possibilities.
“Right under our noses there was this massive communication channel that we had just not been studying,” Mok told Endpoints News. “If we had known that and started working and studying that, maybe we would’ve had better organoids, we would’ve been able to solve a lot of technical challenges.”
So Mok launched a new company: Mantra Bio. Founded in 2016, it is now emerging from stealth mode with $25 million in Series A funding led by 8VC and Viking Global Investors. Mantra joins a series of other companies — most prominently Codiak Biosciences — who are trying to understand this natural messaging system and copy it to build stealthy couriers that can slide drugs into hard-to-reach places and shuttle gene therapies past the body’s natural defenses.
“I know the term ‘platform of biotech’ gets used a lot,” 8VC investor and Mantra board member Francisco Gimenez told Endpoints. “But it is truly a platform by which we could conceive of delivery of all sorts of therapeutic agents.”
Still, Gimenez acknowledges, there are a lot of challenges left to solve. Exosomes, also known as extracellular vesicles, are tiny lipid sacs, around a thousandth the size of a cell, that contain micro-strands of RNA or other biological cargo and shuttle them around the body, to different cells and organs. They are found in all life, and they have evolved to carry those RNA messages throughout the body without attracting attention from the immune system.
That makes them an ideal drug delivery mechanism. Codiak’s first program was an exosome to target KRAS, an oncogene that has been notoriously hard to hit because the proteins lack a natural groove for a small molecule. More recently, they’ve signed up with Sarepta to develop the first multiple-dose gene therapy; traditionally gene therapy has been single-dose in part because immune systems evolve defenses against the vector used to deliver it.
Yet exosomes are complicated — “very, very complicated,” Mok said.
On top of just the lipid sac itself, there are also numerous proteins on top of them that are required to silence the immune system and numerous proteins that are involved in assuring the vesicle docks and enters its target cells. “We’re talking about super, super small hundred-nanometer vesicles where nature just basically evolved it to be the best drug delivery vehicle there is,” he said.
It’s no surprise, then, that no exosome drugs have entered the clinic so far, or that Codiak struggled to develop its KRAS program and ultimately put it on the backburner. Gimenez said he’s been watching the field for years, from the time when researchers were excited about the potential but lacked the tools to even look at individual exosomes.
“It’s been kind of a pain in the ass to actually get it working,” he said, referring to the overall field.
Mantra Bio hopes to solve some of these problems by using a computational platform to first find targets and design exosomes and then building a set of them in the lab. So far they have in the tens of exosomes, Mok said, but they hope to soon escalate to over 100. They’ve also invested early in the manufacturing technology to prevent some of the bottlenecks that have held up other researchers.
For now, the company is keeping its particular potential close to the vest, but they plan on filing an IND by 2022 or 2023. Mok also said they could partner with other biotechs, such as Moderna or Alnylam, in helping deliver their RNA drugs.
“We’re certainly really excited about gene therapy and rare diseases and the undruggable space,” he said.
Update: The first quote in the story contained a mistype. It has since been updated.