Cancer treatment has evolved from the use of chemotherapeutic anti-tumor drugs to targeted therapies to monoclonal antibodies to immunotherapies to new, personalized therapeutics.
Precigen, Inc. PGEN 7.25% is a biopharma pursuing a differentiated approach toward a cancer cure, and CEO Helen Zabsevari, who has strong academic credentials and has found equal success in the business arena, spoke with Benzinga about the company's products and platforms.
Gene Therapy Basics: One of the cutting-edge innovative approaches that evolved in the 21st century is the use of cell and gene therapies to treat cancer.
Gene therapy uses specialized immune forces that can recognize tumor cells very specifically, Zabservari said.
These T cells are trained and given the capability to kill tumor cells without the use of chemotherapy or targeted therapy or small molecules, the CEO said.
Precigen is unique and differentiated in that it has been developing and evolving platforms that are key in the field of gene therapy and for the activation of the immune system, Zabsevari said.
The basics of precision medicines include insertion of genes that can activate cells, the modality of gene delivery and the number of genes that are requited for activation.
The mode of delivery can be viral or non-viral, and this determines the time and cost involved for the treatment, she said.
Another important aspect is controlling the expression of genes in the activated T-cells, Zabsevari said.
When an army of T-cells is mobilized but cannot be controlled, it will run amok, destroying both the cancer cells as well as healthy cells, she said.
How Precigen Stands Out: Precigen has developed a platform that has every one of these elements, and all under the same roof, Zabsevari said.
"We can now in a totality create a platform for a gene therapy for instance, and a good example of that is with our UltraCAR-T platform," she said.
Conventional CAR-T therapies from companies like Gilead Sciences, Inc's. GILD 0.32% Kite and Novartis AG NVS 0.88% have several shortcomings, Zabsevari said.
The genes expressed in the T-cells are very limited, and these cells can express only chimeric antigen receptors, she said.
No safety mechanism exists to eliminate these T cells if something goes wrong, the CEO said.
The second major problem with conventional CAR-Ts is the constraint on the number of genes that can be expressed with the limited payload of the lentiviruses used to carry the genes, the Precigen CEO said.
The cost associated with manufacturing is anywhere between $250,000 and $400,000, as the cells have to be grown outside for four to eight weeks and quality-checked before returning them to the body, Zabsevari said.
Clinical data from conventional CAR-Ts, TCRs and allogenics shows these cells are alive from two to a maximum of three weeks in a patient, the CEO said.
The $500,000 price tag for one dose, which only lasts two weeks, becomes a roadblock, she said.
Precigen has developed the UltraCAR-T platform to address these issues, Zabsevari said.
The company has designed ultra-vectors with a much higher payload capacity that can simultaneously express three genes within the same vector, the CEO told Benzinga.
This allows putting specific genes that address not only the expression of the CAR-T, but also how the T cell can be advanced and maintained, she said.
Precigen has introduced a safety feature for eliminating the cells if something goes wrong.
How Precigen's Candidates Are Cost-competitive: Precigen has introduced UltraPorator, which is a nucleic acid transfection system that increases the efficiency of transfection, Zabsevari said.
UltraPorator can transfect the company's ultra-vectors to a T cell, and is capable of 4 billion T cell transfections in under 12 minutes in a semi closed system compared to four to six hours with current technology, the CEO said.
It also reduces the risk of failure due to the reduced handling involved, she said.
Precigen has two ongoing trials. One is in ovarian cancer, in solid tumors: PRGN 3005, which is in Phase 1 development.
PRGN 3006 is being evaluated in acute myeloid leukemia at Moffitt Cancer Center, Zabsevari said.
The Administration Of Precigen's Therapy: Once patients enter the clinic, their T cells are separated and transfected with ultra-vectors using the UltraPorator.
The cells are incubated and quality checked the next morning. The cells of the patients are then returned back to the patient — vein-to-vein in under 24 hours.
The membrane-bound IL1, an expression of a specific gene designed by Precigen, is like a backpack of food for T cells, allowing them to expand and persist, Zabsevari said.
https://www.benzinga.com/general/biotech/21/04/20474867/exclusive-precigens-ceo-breaks-down-biotechs-oncology-platforms-technology-differentiators
