New Gates Biomanufacturing Facility a game-changer

GBF sets high expectations

The new Gates Biomanufacturing Facility (GBF) will serve academic, clinical and commercial investigators, both Colorado-based and nationwide, looking to translate their discoveries into clinical-grade products suitable for investigational use in humans.

The GBF operates as a cost-neutral auxiliary service center of the University of Colorado School of Medicine. By end of 2013, the Gates Center for Regenerative Medicine had secured a 15-year lease and $8.8 million in commitments from donors, foundations and campus partners to renovate, equip, retain and operate the GBF through 2018.

The GBF is a Good Manufacturing Practices facility. These are practices are required to conform to guidelines recommended by agencies that control authorization and licensing for manufacture and sale of food, drug products, and active pharmaceutical products. The guidelines provide minimum requirements that a pharmaceutical or food product manufacturer must meet to assure that the products are of high quality and do not pose any risk to the consumer or public.

In one to three years, developing therapies expected to use the GBF include:

• Corneal regeneration
• Cell-based immunotherapies for treating cancer
• Haematopoietic stem cell (HSC) expansion for immune deficiencies and cancer patients who need bone marrow transplants
• Oral mucositis
• Esophageal repair following tumor removal

In three to five years, therapies are expected to use the facility include:

• Trachea and wind pipe regeneration
• Cell-based therapies for cardiovascular diseases
• Cartilage and bone regeneration and cell-based therapies
• Cell-based therapies for inherited skin diseases
• Cell-based therapies for macular degeneration

The GBF is a campus-wide partnership comprised of the Gates Center, Anschutz Medical Campus, CU School of Medicine (SOM), University of Colorado Health, Children's Hospital Colorado and the Gates Frontiers Fund.

Previously at CU Anschutz, development of cutting-edge cell-based therapies involved going out of state to Food and Drug Administration-approved manufacturing facilities. Prior to the new facility, the Gates Center would occasionally run into the problem of bringing top cell-therapy clinicians to campus only to hear them ask, "Where is your GMP facility?"

Say goodbye to that recruitment issue.

The first of its kind within a 500-mile radius, the GBF is a Good Manufacturing Practice (GMP) facility that complies with all FDA manufacturing regulations. "For the first time in the Anschutz Medical Campus's history, the state of Colorado's history, the Rocky Mountain region's history, we now can control our own destiny" in manufacturing cell therapy and protein-based products, Gaines said.

The 14,000-square-foot GBF is located in the Bioscience Park Center, part of the Fitzsimons Innovation Campus on the north side of Montview Boulevard, which is owned and operated by the Fitzsimons Redevelopment Authority. Being across the street from CU Anschutz is important because the Bioscience Park allows both for-profit and nonprofit development.

"We can work for researchers who are at the university, but we can also work for the spinoff companies that they generate," said Timothy Gardner, Gates Center director of finance and operations. "If we were on this side of the street (the nonprofit educational campus), we would not be able to work with the spinoffs. That's a big thing."

Dennis Roop, PhD, was recruited from the Baylor College of Medicine in 2007 to be director of the new Gates Center for Regenerative Medicine. When the new west wing of the Bioscience Park Center became available two years ago, Roop knew that what he'd envisioned all along, a GMP facility that combined cell therapy technology and a protein production suite to produce biologics, would soon come to fruition.

"That proximity is huge," Roop said. "It's a facility where scientists and clinicians can just walk across the street, manufacture their product, and walk it back to the hospitals."

Vision for breakthroughs

The facility surely would have gratified Denver industrialist and philanthropist Charles Gates, who suffered from macular degeneration. Prior to his death in 2005, Gates told his family of his belief in the potential of stem cell-based therapies and the promise of future scientific breakthroughs.

Dennis Roop, PhD

A donation from the Gates Frontiers Fund provided the initial funding to bring Roop (pictured below) and his lab to Colorado along with a subsequent equal match from the University of Colorado Foundation to support the center's research and programs for five years through 2015. Recent contributions from the Gates Frontiers Fund as well as gifts from a number of private donors, including the Temple Hoyne Buell Foundation, secured the space for the new facility in the Bioscience Building and funded a portion of its renovation and equipment. Fittingly, the facility will be dedicated to Charles Gates and his vision.

The Gates Center for Regenerative Medicine is a consortium center, with 72 members, about half representing the Anschutz Medical Campus and the rest from National Jewish Health, CU Boulder, Colorado State University, Colorado School of Mines and private industry.

The facility offers ample opportunities for collaboration. For instance, School of Mines bioengineers are working with Karin Payne, PhD, (Gates Center, SOM) on scaffolds that support bone growth. Also, cell-based therapy trials being performed on large animals at the CSU Veterinary School will benefit from the human translation capabilities of the GBF.

"Regenerative medicine is this collaboration of different disciplines and cell therapies in that we bring a lot of different things together here," Gardner said. "We're working with ophthalmology, orthopedics, immunology and dermatology, just to name a few."

Meanwhile, grant money is flowing in for member research. By the end of 2014, 39 Gates Center members had received almost $120 million in research grant funding, with 75 percent coming from the National Institutes of Health (NIH). Taiga Biotechnologies, a company founded by Gates Center members Yosef Refaeli, PhD, and Brian Turner, PhD, both with the SOM, has received grants totaling $2.1 million from NIH. Taiga uses stem-cell technology to develop therapies for diseases such as cancer, HIV and influenza, and hematologic conditions and is currently funded to support its planned clinical trials.

The bioscience private sector—the Gates Center aims to generate technologies that create at least five startup companies within five years—and CU Anschutz schools and colleges will benefit from the new facility's services. The GBF offers cell therapy and protein/biologics manufacturing rooms, along with cell and protein development laboratories. Overseen by expert staff, the facility offers process development and scale-up from bench to bedside, manufacturing of both cell therapy and protein-based products to GMP standards, and thorough process documentation.

Academic researchers, clinicians and biotechnology companies will use products generated by the GMP facility for early-phase clinical trials.

Talent recruitment

"From the point of view of both the university and the hospitals, in being able to recruit top-notch talent that's doing cutting-edge therapies, having the facility is really huge," Roop said.

There are now 24 academic GMP facilities nationwide, but only six, including the new GBF, with the capacity to not only grow and expand human stem cells, but also manufacture protein-based products for human applications. Importantly, with easy access to patients at University and Children's hospitals, the Gates Center is able to conduct on-site clinical trials.

Some of the collaborations involving the GBF span the globe. For example, colleagues of Roop's in Italy have devised a process to regenerate corneal cells. This is a breakthrough for people who have suffered chemical burns or infections to their corneas. The researchers spun off a biotech company that recently received commercial approval for a stem cell-based therapy, and the company is using a GMP facility in Italy to produce the clinical-grade therapy.

"They've been out twice to talk about developing that technology here, and the limitation has always been we don't have a GMP facility. But now we do," Roop said. "This is the type of thing where we can pull in other investigators. ... The great thing about Denver is you could service all of North and South America because it's an overnight flight from anywhere. So this is the kind of thinking that the Gates Biomanufacturing Facility has generated: We can think big."

Roop hopes to translate his research of inherited skin fragility syndromes, or blistering skin disease, which can be fatal, into one of the first clinical-grade trials out of the GBF. "Skin is a great target because it's visible, you can monitor it, and there's currently no cure for these diseases," he said.

Adam Klafter

Roop's research, for example, gives hope to many patients, including 13-year-old Adam Klafter (at right) of Atlanta, who, along with his family, recently visited Roop and toured the new GBF. Because of a rare gene mutation, Adam suffers from epidermolytic hyperkeratosis (EHK), which causes skin to blister and tear at the slightest touch. "With the help of Dr. Roop, and this new facility, we hope that one day he will know a different skin," said Adam's father, Mark Klafter.

The focus of Gates Center investigators' work is adult stem cells as opposed to embryonic stem cells. "It mainly has to do with being the state-of-the-art," Gardner said, "because when you work with adult stem cells, and they're used in the clinical treatments, you reduce the risk of rejection."

Roop said the new GBF is also "very exciting" to the pharmaceutical industry because immunotherapies are a big part of what the facility will produce. In many cancer therapies, where immune cells are removed from the blood to be modified and expanded, but can't be frozen, the patients must be near the facility. "The patient will be in the hospital for the two or three weeks while the cells are being expanded," Roop said. "So if the maker of a cell-based therapy wants to bring that type of immunotherapy trial to Denver, we have the facility, which is huge for the hospitals."

Complete medical ecosystem

Roop is well-connected to the many stem cell-related therapy projects taking place regionally and nationally and works to link researchers together. "He'll often say, 'Did you know so-and-so is doing this?' ... and then you'll see someone's research being applied to multiple projects," Gardner said.

The synergies being created in this burgeoning field—with the Gates Center for Regenerative Medicine and now the GBF at the center—ensure an ever-enlarging membership of researchers and clinicians at CU Anschutz.

"We're now going to be able to develop our own research, products and therapies, but also bring outside concerns into Colorado to develop their cell lines, and we hope that attracts business," Gaines said.

The facilities complete the CU Anschutz medical ecosystem that begins with basic research and flows from manufacturing and clinical trials to optimum patient care. This big step ensures that the campus will stand out even more as a medical destination and a draw for world-class talent in stem cell research.

"Everyone who comes here is just blow away by the state-of-the-art campus," Roop said. "And now having this facility, being so convenient and in walking distance, it's just a dream come true."

For more information about the Gates Biomanufacturing Facility and the Gates Center for Regenerative Medicine, please contact Patrick Gaines at Patrick.gaines@ucdenver.edu or 303-724-6141.