The $10 million series A round raised by Platelet Biogenesis Inc. (PBI) should move its bone marrow-mimicking system to the clinic within three years, chief business officer Sven Karlsson told BioWorld. "Our initial focus is definitely on creating real functional generic platelets that should be equivalent to your platelets or my platelets," he said. "That in itself is a big challenge. After we've created the bioengineered platelet platform, there's already a fair amount of literature out there showing that you can use platelets to do various things within the body, for example, using them as a drug delivery vehicle," and proof-of-concept efforts in such realms would begin next.

Platelets now are sourced entirely from human volunteer donors and the growing industry amounts to $20 billion-plus. Boston-based PBI was spun out of the academic labs of Brigham and Women's Hospital and Harvard Medical School in 2014. That year, collaborating with Ocata Therapeutics Inc., of Marlborough, Mass., PBI showed that it was feasible to generate functional megakaryocytes from research-grade human induced pluripotent stem cells (hiPSCs). Tokyo-based Astellas Pharma Inc. bought Ocata for $379 million. (See BioWorld Today, Nov. 11, 2015.)

Starting with the hiPSC line offered genetic control of the product and supported future development of human leukocyte antigen-matched platelets that could be customized to recipients and targeted to specific diseases. The method also allowed for freezing of megakaryocyte progenitors, which could be thawed and differentiated to mature megakaryocytes within a few days, potentially making possible on-demand production.

The approach uses a serum- and feeder cell layer-free protocol which decreases the risk of an immunogenic reaction in humans, at the same time ensuring improved scalability, increased time efficiency from megakaryocyte progenitor to platelet, and decreased overall cost of generating platelet units.

"People have been trying to create platelets for decades now," Karlsson said. "There have been two approaches. One is to create synthetic platelets, where you're mimicking one specific aspect of the platelet, which is usually the clotting function. Those have not really worked, because platelets do all sorts of things in the body beyond just clotting. When you mimic that one aspect, you fail to mimic the other things and either the body clears it immediately or you risk creating clots where you don't want them. The second approach, which is what we've taken, is to mimic the process through which platelets are created instead of mimicking the product. Theoretically, if you mimic the process correctly then you should create a real platelet that does all the things we know platelets do, but also all the functions that platelets have in the body that we don't even necessarily know about yet."

'Zero access' in much of world

PBI's effort combines new concepts in bone marrow physiology with biologically-inspired tissue engineering. "The real challenge has always been scale – making enough platelets per parent cell in order to make this potentially competitive with a human donor," Karlsson said. It's a hurdle that PBI conquered by "creating this microfluidic device where we mimic human bone marrow and, by exerting shear forces on the cells similar to flowing blood as they mature, we're able to dramatically increase the yield. Other people have done great work solving other pieces of it," he said.

The discovery in 1994 of thrombopoietin by Thousand Oaks, Calif.-based Amgen Inc. drove the generation of the first human platelets in 1995, but it wasn't until 2006 that the invention of hiPSCs allowed for the scalable generation of genetically consistent stem cells. The third major advance was made in 2014, when researchers solved how to trigger megakaryocytes to make platelets at yields necessary for clinical/commercial application. Human iPSC-derived platelets are poised to become among the first stem cell-derived tissues advanced for clinical use and represent a major first step toward a sustainable, donor-free blood system, PBI said.

"The first year or so was really just applying for grant funding, trying to get it off the ground," Karlsson said. PBI moved into lab space and hired the first employee in 2015 and has "been growing pretty steadily since then." The company has 10 employees and "over the next year or so, we'll approximately double that," he said. "We definitely are pretty capital-efficient in terms of how we run it," the team having become accustomed to "very limited budgets to date," he added. "I don't want to say we're thrifty – if something matters, we'll spend money on it. We're focusing all of our energy on developing the science, which is the most important thing for us at this stage."

Karlsson said the device would be about the size of tablet computer but square in shape. "You would take the precursor cells, the parent cells, connect those to this device and then run it over a period of 12-24 hours, and that would generate a single unit of platelets that would be equivalent to donor units," he said. "We have to scale up to get there, but that's the design we're targeting," and the company is "trying to think about how it could be used in different settings," beyond selling platelets directly to hospitals.

The approach could be useful for the military and in disaster-relief areas, Karlsson said. "We need to be able to produce a unit of platelets in a geographic footprint, [and] the amount of space required to do that has to be less than having a bed where a donor is sitting on it and you're collecting platelets. We're trying to fit the technology into the existing system."

Access to platelets today is limited to major cities in developed countries, Karlsson noted. "Even in the U.S. if you go outside the major cities to suburban areas or rural areas, it can be very hard to get platelets. For the vast majority of the world, there is zero access to platelets at all," because platelets from human donors bear only a five-day shelf life.

Also working in the platelet space but taking a different approach is Kyoto-Japan based Megakaryon Corp., and academic research is ongoing. PBI is collaborating with the University of Cambridge in the U.K., where the team led by Cedric Ghevaert has done "phenomenal" work, Karlsson said. "They're mostly focused on going from the stem cell to the parent cell," he added.

The series A round was led by Qiming U.S. Healthcare Fund and included Vivo Capital, VI Ventures, Adena Partners, eCoast Angels, and others.