Precise Bio Developing ‘4-D’ Process for Biofabricating Tissues, Organs
Aryeh Batt envisions a day when a young boy needing a heart valve will get one fabricated from his own cells that will grow along with his body as he matures and be free of rejection by his immune system. Or a woman with impaired vision will get newly made corneas instead of having her own corneas repaired through Lasik surgery.
“Regenerative medicine is the future,” says Batt, co-founder and chief executive officer of Precise Bio, a regenerative medicine startup company in Winston-Salem.
Precise Bio has developed a laser-based biological “printer” that can fabricate tissues and organs from living cells in three dimensions, just as they are structured in the body. Patients may one day receive custom-printed transplants from the company to treat a wide range of diseases and conditions, starting with ophthalmology indications.
“We want to achieve the holy grail of having complex organs that can be biofabricated,” Batt says. “Our vision is to bring regenerative medicine technologies to the clinic to improve quality of life and save lives.”
That vision inspires the company’s 20 employees daily, he says.
“People come to work here very excited because they know they’re changing the future of health care,” Batt says. “It’s not just developing technology or coming and getting a salary.”
Physics meets biology
Batt, a U.S. citizen who grew up and went to college in Israel, worked in product research and development in various industries for many years. With his training and experience in physics and electro-optics engineering, he started developing a laser-based bioprinter that could deposit living cells, one by one, onto a surface, building tissues layer by layer into a desired shape without damaging the delicate cells.
What he didn’t have was expertise in the biology of cell regeneration to optimize the printing process.
“They have to work together,” he explains.
Batt found that expertise half a world away in Winston-Salem, N.C.
“I heard that one of the worldwide leaders in the field was Anthony Atala,” he recalls.
Atala, a urologist and professor, was the first in the world to successfully implant a laboratory-grown organ into a human while working at Boston Children’s Hospital. Today he directs the Wake Forest School of Medicine’s Institute of Regenerative Medicine (WFIRM), which is working to grow more than 40 different organs and tissues in the laboratory.
When Batt first met with Atala to describe his bioprinter, Atala recognized the technology’s potential for advancing regenerative medicine. The two men, along with, Shay Soker, Ph.D., a professor of regenerative medicine and biomedical engineering at WFIRM, co-founded Precise Bio in 2015.
Atala is the company’s chief medical officer, while Soker is its chief scientific officer. Their roles with Precise Bio are separate from their work at WFIRM.
Precise Bio is headquartered in Winston-Salem’s downtown Innovation Quarter, where it leases about 4,500 square feet of laboratory and office space, including a GLP (Good Laboratory Practices) lab that’s being finished. Ten employees focus on the biological challenges of tissue and organ fabrication.
Another 10 employees at the company’s subsidiary in Shoham, Israel, are refining the bioprinter so it can consistently manufacture tissues and organs to scale.
“There is very tight collaboration between the teams,” Batt says. “I think this is one of the strengths of Precise Bio because many things are connected.”
‘Achieving good tissues’
Bioprinting is a complex enterprise that draws on multiple disciplines including physics, optics, mechanical engineering, software engineering, cellular and molecular biology, biochemistry, biomaterials, tissue engineering and more.
“Precise is bringing the outcome of these technologies – biofabricated tissues – to clinicians so they can bring them to patients,” Batt says.
While several companies sell 3-D bioprinters for research, “they don’t have the biological knowledge to process tissues,” Batt says. “We have biological knowhow and the printing, and we can optimize them to achieve good tissues.”
Precise Bio calls its process 4-D biofabrication to distinguish it from other bio-fabrication approaches.
“We have superior printing technology and biological processes that lead to good integrity of tissues,” Batt says.
The company’s biofabrication process begins with the harvesting of cells from a patient or donor. The cells are cultured in incubators until they proliferate into workable quantities, then are mixed with a “bio-ink.” The bio-ink, a composite material made from human tissue, growth factors and other substances, maintains the cells’ properties and gives them structure in the newly fabricated tissue or organ.
The cells and bio-ink are mixed in a cartridge, similar to those found in office printers. The mixture flows through a print head, and laser technology deposits the cells layer by layer onto a substrate, forming anatomical structures like those found in the body.
The structured tissue goes through a maturing process in a bioreactor and incubator to achieve tissue integrity and functionality. “This is the fourth dimension” in the company’s 4-D process, Batt says.
Finally, the fabricated tissues or organs are tested for quality prior to transplantation.
The biofabrication “is a very structured process” that has been well established and proven by Atala over two decades, Batt says.
Early focus on ophthalmology
Precise Bio’s initial work is focused on ophthalmology applications and generating preclinical data to support them. The ophthalmology field is quick to adopt innovation and has a “fairly clear” regulatory path for product approvals, Batt says. Plus the eye is composed of layered cells, making it suitable for 3-D printing.
“We looked at ophthalmology as low-hanging fruit and an initial field to build our first business unit, Batt says.
The company is working first on corneal transplants – a good field for establishing proof of concept because various parts of the cornea don’t have blood vessels, nerves or immune system response, allowing corneal cells to be harvested from donors other than the patient.
“There is a lack of donated corneas on the scale of 10 million worldwide,” Batt says.
Precise Bio is the first company to transplant a 3D-printed cornea graft in animals, and its printer can produce a cornea every five minutes, or 20 per hour, from human corneal cells.
Preclinical work is being done in mice and in rabbits, which are a good model for human eyes, Batt says.
A first-in-humans clinical trial is targeted for early 2021, perhaps in collaboration with partner companies and research centers, Batt says.
Other product possibilities include a retinal patch, vision-correction lenticules (tissues that change the cornea’s curvature and thickness) and solutions for ocular surface diseases.
In addition to its ophthalmic pipeline, Precise Bio is in the early stages of developing a 3-D cardiac tissue patch for patients who’ve had heart attacks. Implanting a bio-fabricated patch could restore the viability and function of heart muscle tissue.
The company is also evaluating other applications in orthopedics, dentistry, dermatology and wound care.
Globally the regenerative medicine market was worth $28 billion in 2018 and will grow to $81 billion by 2023, according to Kelly Scientific. It is one of the fastest-growing sectors in the life sciences with a compound annual growth rate of 25.4% expected between 2016 and 2022, according to a report by Market Research Future.
Series B financing on horizon
Precise Bio has raised close to $10 million in private investment to date. A $7 million Series A round was led by an Israeli venture capital firm and included investors from the United States, Canada, Europe and Israel.
The company plans to start a Series B round in the third quarter of this year, Batt says. It is arranging $6 million in bridge financing that should carry the company to the middle of 2020.
Making progress toward clinical applications is the company’s greatest challenge, he says, just as it is for other young bioscience companies working in health care.
“Precise is still a startup company,” he says. “As that, we have to achieve technology milestones with a limited budget as every startup does.”
The company is developing strategic partnerships with other regenerative medicine companies, and “we are getting interest from all the major leaders in the field,” he says.
Bullish on Winston-Salem
Precise Bio located its headquarters in Winston-Salem for an obvious reason: “Two of the company founders (Atala and Soker) are across the street” at WFIRM, Batt says.
The company also has an agreement to use some of WFIRM’s scientific equipment.
“We’ve found it to be very comfortable and supporting,” he says. “We feel that this area in Winston-Salem is a biotech environment that is growing, and we are part of that.”
Batt spends about a week to 10 days per month working in North Carolina before boarding a plane for a 10-hour flight to Israel, where he has a home and a family.
“It’s very convenient here,” he says. “It’s a very good environment for living and also for innovation.”
That assessment is no surprise to Nancy Johnston, executive director of the North Carolina Biotechnology Center’s Piedmont Triad office, who helped introduce Precise Bio to key industry players in the company’s early days.
“North Carolina and specifically the Piedmont Triad are on the global forefront of advancing emerging growth companies like Precise Bio,” Johnston says. “We have world-renowned regenerative medicine and tissue engineering expertise, and we have multi-disciplinary collaborations within academia and industry.”