Mention the terms ‘cell therapy’ or ‘regenerative medicine’ and many in the general public are still confused as to what those terms actually mean. But those in the know understand that cell therapy is a growing and thriving industry, with great potential to change the face of modern healthcare.
Progenitor Cell Therapy (PCT), a cutting-edge contract development and manufacturing organization with facilities in Allendale, NJ, Mountain View, CA and Irvine, CA, is working to help make tailor-made therapies a reality for a wide range of patients. Through a combination of expertise, technological achievements and business acumen, PCT is paving the way in the field of cell therapy, a small subset of the pharmaceutical industry.
Regenerative medicine and cell therapy is sometimes considered the fourth pillar of medicine alongside traditional pharmaceuticals, biologics, and medical devices. PCT holds a unique position as a contract developer and manufacturer that is entirely focused on this rapidly growing market. PCT has evolved alongside the relatively young cell therapy industry, and over its past 15 years of operation, has acquired a wealth of expertise in this market segment, emerging as a leader in the field.
History and Background
PCT’s history is tied directly to Robert Preti, Ph.D., the company’s President and Chief Scientific Officer. Back in the mid 1980’s, before there was a term for cell therapy or regenerative medicine, Preti began his career working for a small start-up company. The company had been founded by two post-docs who knew Preti from grad school. The company was looking to grow bone marrow in a three-dimensional manner and store it – much like cord blood and adult stem cells are now stored.
Preti was tasked with devising a system to grow the bone marrow, as bone marrow is not easy to harvest and only a small amount can be collected at a time. The founders reasoned that should they be able to expand the cells in three dimensional constructs, these small amounts of cells collected from young, healthy individuals could someday be expanded and used for the donor in the event s/he required a bone marrow transplant. As Preti explains, “We built these constructs and we had some difficulty trying to get the process to work.” But in doing so, Preti and the team made another discovery – the constructs they were using to try and grow bone marrow looked more like skin than bone marrow. So they started another company, called Advanced Tissue Sciences, and created a product called DermaGraft which is still being sold today.
After this initial success, Preti’s career next took him to the New York Blood Center where he worked on bone marrow transplantation at a time when this procedure was just starting to be used for chemotherapy and radiation patients whose bone marrow was destroyed by these aggressive treatments. The bone marrow transplants Preti worked on allowed physicians to remove the marrow, attempt to purify it from contaminating tumor cells (autologous transplant) or active lymphocytes (allogeneic transplant), save it, and then return it to the patient when needed. It was also at this time that graft engineering became a reality. As Preti explains, “It made no sense to return bone marrow that might be full of tumor cells back to the patient. Therefore, graft engineering (tissue replacement) gave rise to another industry which we now call cell therapy and regenerative medicine. We are now able to perform experimental manipulation to transform cells of the body into replacement parts for other parts of the body or to provide other mechanisms to treat disease.” During this time, he was also part of the founding of the International Society for Hematotherapy and Graft Engineering (ISHAGE), now called the International Society of Cell Therapy (ISCT).
By 1996, Preti relates, his own vision for the role of a contract provider of these types of services was broadened beyond the manufacturing and supplying of bone marrow, and he became interested in other clinical aspects of the cell therapy business. “I wanted to create hearts for people, and be part of developing cures, not just palliative therapies, as important as they had been to the advancement of medicine. And it became clear that there was a worldwide industry developing that could use the type of assistance that we were providing, although we would need to commit to investing in more sophisticated facilities, systems, staff and new technologies to really make it happen.”
Preti founded PCT in 1997 with a colleague, Andrew Pecora, M.D., then the Hackensack University Medical Center’s (HUMC) bone marrow transplant director, whom he met when HUMC was a client of the New York Blood Center. Pecora also had a similar vision for the future of cell therapy and regenerative medicine. Preti explains, “We made a good team. Andrew brought clinical experience to the picture; he knew the patients, he knew what the doctors wanted to see, and he knew what these therapies needed to look like when they reached the bedside.” With their combined vision and experience, Preti and Pecora launched PCT, the first for profit contract manufacturing organization in the field.
Early Successes and Growth
PCT started in a small manufacturing facility in Hackensack, NJ in a facility commissioned in HUMC in March, 1999.
One of PCT’s earliest successes was securing Dendreon as a client. “That was really big for us,” said Preti. “Working for them brought us to a new level where we were performing Phase I and Phase II manufacturing in a clinical setting under the auspices of FDA control. This was all new, as in 1996 there was not much of a regulatory environment for cell therapy manufacturing.”
Through this whole “revolution” as Preti describes it, PCT assumed a leadership position in the industry, for example, in regards to the FDA in establishing regulations, and adapting what the industry does according to the GMPs, which were both new concepts to the industry.
“We were really pushing the edge and moving the bar in the industry – we were in the right time and the right place to grow cell therapy manufacturing from the ground up,” Preti said.
One example of the unique need for niche contract manufacturers is for support of the specific processes required for Patient Specific Cell Therapy or PSCT. PSCTs can take one of two forms – cells can be taken from one donor and administered to another recipient (allogeneic) or taken from the patient and given back to the patient (autologous).
“This issue of patient specific processing is just one way that we differ from the traditional pharma industry,” says Preti. “To take a drug and develop it on a one-to-one basis, as opposed to taking a quality system and spreading it out over 100,000 bottles of a drug, means that our processes and systems are much different to make this happen in an effective and quality way. With a PSCT, everything is concentrated on that one product – batch records, materials control, environmental monitoring, testing, release testing – it’s all concentrated for that one patient, and then it all has to be repeated for the next patient.”
Growing in Size and Capability
In 2002 PCT took a very important step forward in advancing their business by assuming from Dendreon its Mountain View, CA facility and west coast based clinical manufacturing activity. As the facility was producing product only for Dendreon’s west coast clinical trial activity, the facility was being underutilized, and the idle capacity of the entire facility resulted in unreasonable and unnecessary overhead for Dendreon. Accordingly, PCT purchased the operations, assuming Dendreon’s facility, their personnel and the manufacturing for Provenge®. Estimates are that this assumption by PCT likely saved Dendreon many millions of dollars on their west coast clinical trial activity. Since then, PCT has almost completely built-out the facility, adding five clean rooms, QC labs, and manufacturing development space.
“That facility was important for us because of the geographic location,” says Preti. “It’s imperative that we put facilities near patient populations, because we are shipping live products. At the time we didn’t have the technology to stabilize these products and ship them somewhere where it might take 2-3 days to get there.”
PCT’s east coast facility and the new California facility worked together on a Phase III and a Phase IIIb trial for Dendreon. This activity helped Dendreon launch their product, based in part on the clinical data generated from the use of products produced at PCT. As a result, Dendreon received a BLA and built a new facility in Morris Plains, NJ to manufacture their product. PCT retained and has continued to expand capacity in the Mountain View facility that today provides manufacturing services for other clients in the industry, and an important west coast footprint for PCT.
PCT was growing its facilities and advancing its expertise, developing full SOPS, then moving into qualifications and release testing. In considering PCT’s transformation, Preti raises the phrase that people use in the pharma industry, “the process is the product and the product is the process.” He explains why it is so important to understand the process and the product, and how that phrase is particularly true in cell therapy.
He clarifies however, “I’m not a big fan of this statement. As processes tend to change over time, your product may change too, and as such, understanding the product is as critically important as understanding the process.”
Preti continues, “Back in 2005 PCT led the field to focus on the need to more fully characterize the product. Product characterization was the most important criteria in product development as it is the spine around which all product development occurs, allowing for change control, automation, multisite manufacturing competency assessment, and technology transfer – in short this would allow product comparability assessment. A well-characterized product is the basis upon which all product development occurs – if you don’t understand your product you won’t succeed.”
Making the Business Work
As a service provider in a developing industry, PCT needed to generate a significant cash flow.
“It wasn’t enough to build just a business if it wasn’t sustainable over the long run,” says Preti. “We had bigger visions. We saw PCT as the portal through which people could develop their products and processes.”
PCT adopted a “come to us” philosophy for products and processes that allowed PCT to demonstrate its expertise and experience. This model afforded clients the opportunity to turn on and off their development process as need be – something they could not do if they had their own facilities. Preti found early on that this model fits the clients’ needs, and offers flexibility to both PCT and the clients.
“Contract manufacturing is a perfect solution,” says Preti. “Theoretically if you are not using people for one product they can be used for another project. We are in the business of expert capacity utilization.”
Creating a New Business Model
Another way that PCT adjusted their business model for long term sustainability and growth was by the creation of its own cell therapy products. As one example, they seized upon some favorable market indicators with the creation of Amorcyte, a PCT company that used bone-marrow derived stem cells to treat patients who have just had a heart attack. PCT developed the technology using their own staff and infrastructure and worked on Amorcyte until it was ready to start on a Phase I trial. They then spun it off as its own standalone entity. In doing so, PCT locked in all the revenues to perform the clinical trial and the commercial work.
Soon after, PCT duplicated this business model with a new company called Athelos, which used immunotherapy and T-regulatory cells to treat autoimmune diseases.
Even with these two product lines and bi-coastal facilities, PCT was still seeking revenue opportunities for more clean rooms, staff, marketing, and other activities. At the time PCT was providing cell processing and storage services for a company called NeoStem. NeoStem wanted to open a manufacturing facility in China, so PCT became involved in building them a facility in Beijing.
PCT was acquired by NeoStem in January, 2011. “NeoStem liked the work we did for them, and admired our foothold in the industry. Our companies also held similar visions for the future of cell therapy, so the match of NeoStem and PCT worked well,” says Preti.
In 2011, Neostem also bought Amorcyte, and had absorbed the Athelos technology as part of the original transaction. Both programs are now seminal parts of NeoStem’s current development pipeline. PCT provides services to treat patients with cell and tissue therapies, including the processing for blood and bone marrow stem cell transplants used following radiation and/or chemotherapy for certain cancers, in particular, leukemia, lymphoma and myeloma. PCT also provides services to individuals for the private collection, processing and storage of umbilical cord blood units and adult stem cells under the name NeoStem Family Storage. This enables healthy individuals to have their stem cells or those of their infant collected and stored for personal therapeutic use in the future, as and when needed.
In addition, through NeoStem’s recent acquisition of California Stem Cell, PCT is now utilizing its extensive experience in creating dendritic vaccines to support dendritic cell manufacturing for NeoStem’s expected phase III international trial for the treatment of metastatic and treatment-resistant melanoma.
As part of the company’s forward looking vision, PCT has recently launched its Engineering & Innovation Center (EIC), one of the first development programs in the industry that is responding directly to the major challenges that are facing the manufacturers of cell based therapeutics. Preti and the PCT team have committed the time and resources to innovate, engineer and automate fundamental cell therapy processes with the goal of enabling the cell therapy industry to succeed in a commercial setting. The EIC has been received with great excitement by the industry.
The EIC team is aggressively evaluating current technology and processes to define them in a way that can be applicable to many different therapeutics. Through the EIC, PCT also partners with providers that offer specialized technologies and tools, collaborating to modify existing tools and develop additional approaches to deliver greater efficiencies early on in the development and manufacturing process.
Having honed their business and technology capabilities, PCT is looking optimistically to the future. “We see ourselves as having a powerful, combined engine for progress,” says Preti. “We view ourselves at the core of the industry, and we will continue to work to grow our revenues by providing our services and expertise to more clients. Today we are also garnering the attention of different types of customers, for example, we note an increased interest in the cell therapy manufacturing space by big pharma.”
He continues, “We see ourselves as a market leader, and this momentum we have gathered continues to drive us into much more sophisticated manufacturing and development processes, and we believe ultimately, more commercial manufacturing for our clients’ products as well as potentially our own.”