PharmaCyte Biotech is developing targeted cellular therapies for cancer and diabetes using its live-cell encapsulation technology, Cell-in-a-Box, which was licensed from Austrianova.
By encapsulating genetically engineered human cells that activate an inactive chemotherapy drug – a conversion that normally occurs in the liver – the company hopes it can provide targeted cancer treatment with few or no treatment-related side effects.
PharmaCyte CEO Kenneth Waggoner explained the capsules are implanted as close as possible to the patient’s tumor site, where they work as “little factories” to activate the chemotherapy drug.
The outer shells of the capsules made using the Cell-in-a-Box technology are composed largely of cellulose, which the immune system doesn’t identify as a foreign material. Cellulose also is very stable and doesn’t break down, as opposed to other encapsulation materials, such as alginate, explained Dr. Gerald Crabtree, chief operating officer of PharmaCyte.
The encapsulated cells can be frozen and stored for several years, and when thawed, are recovered with about 95% cellular activity, Crabtree added.
“There is no other material, including alginate, that you can encapsulate cells with, then freeze them down and thaw them out and have them recover activity to nearly the same level,” he said. “So it’s completely unique in many respects.”
The company is initially targeting pancreatic cancer, a difficult-to-treat solid tumor cancer with a high mortality rate. The planned Phase IIb trial is designed to determine how effective and safe multiple courses of ifosfamide will be in patients with locally advanced, non-metastatic, inoperable pancreatic cancer (LAPC).
“We’re not going after a simple target here,” said Crabtree. “We’re going after one of the hardest targets you can go after.”
If the therapy works as the company believes, Waggoner said it could change the way solid cancer tumors are treated.
Outsourcing as a virtual biotech company
PharmaCyte is a virtual biotech company, and as such, outsources nearly all of its activities, including manufacturing.
“Outsourcing sometimes presents difficult challenges that can completely disrupt a company’s clinical development timeline,” said Waggoner. “In our case, it has.”
The company previously was working with an Italian contract manufacturing organization (CMO) that began missing deadlines and failed to supply requested information on a timely basis, explained Waggoner.
It has since made the decision to work with Eurofins Lancaster Laboratories in Lancaster, PA. The company has taken over the project and is growing the genetically altered cells that will be used in upcoming clinical trials. It recently shipped cells from PharmaCyte’s master cell bank (MCB) to Austrianova’s encapsulation facility in Thailand.
Post-encapsulation testing will provide additional data required by the US Food and Drug Administration (FDA) to be included in PharmaCyte’s Investigational New Drug Application (IND).
The project is a major undertaking, Waggoner said, and PharmaCyte has lost more than six months in its march to the clinic due to supplier challenges.
“We did a great deal of due diligence and interviewed several suppliers,” he added. “The difference between the folks we were dealing with and Eurofins is night and day.”
In addition to switching cell suppliers, last year the company also ran into problems with its cell growth media supplier, which struggled to meet demand. “The company we get the media from is the sole supplier in the world for this media,” said Crabtree, who explained the delays that resulted cost the company several more months in its development timeline.
A veteran of the cancer drug development industry, Crabtree added that this is “something that happens fairly often … I’ve seen all kinds of problems from all angles.”
“When you put a timeline down on a piece of paper, particularly at an early stage in the development process, it is rare that such a timeline is completely adhered to, hardly ever, in fact,” he added.
Clinical trials and costs
The company is operating on multiple tracks, Waggoner explained. One of the next steps will be selecting a contract research organization (CRO) to conduct the trial.
PharmaCyte has enlisted the help of a consulting firm, Practical Clinical, which Waggoner said functions as the “right hand” of the company’s chief medical officer.
Four CROs are moving forward to a formal selection process, said Waggoner, who is looking for firms with experience in cancer, particularly pancreatic cancer, as well as a solid overall reputation.
Crabtree said it is also important to have a competent – and confident – clinical research associate (CRA) staff. CRA turnover and employee retention is also an important factor in choosing a CRO, Waggoner added.
The clinical trial is expected to run somewhere between $15 and $17m.
“For me, it’s surprising how much money is involved and the amount of money a company can be charged for all the different aspects of clinical trials like ours,” said Waggoner. “It’s shocking, the amount of money.”
In addition to trial costs, it is estimated that all of the companies involved with the Cell-in-a-Box platform technology since its inception have, collectively, spent around $50m – “and it’s never really seen the light of day in the US,” added Waggoner.
The initial trial in pancreatic cancer will be conducted in the US. In the future, cancer trials will also be done in European countries, such as Germany, Spain, Sweden, and England, potentially among others.
The company is also studying the use of the Cell-in-a-Box technology as the basis for a treatment for Type 1 and insulin-dependent Type 2 diabetes. Future targets in the cancer area include liver cancer, sarcomas, and possibly breast cancer.