The U.S. Food and Drug Administration (FDA) has granted orphan drug status to Precigen‘s PRGN-3006, an investigational CAR T-cell therapy with the potential to provide faster, more durable, and safer treatment to patients with relapsed or refractory acute myeloid leukemia (AML).

A Phase 1 clinical trial (NCT03927261) is ongoing to determine PRGN-3006’s safety and optimal dose. Recruitment is open at the H. Lee Moffitt Cancer Center and Research Institute, in Florida, for patients with relapsed or refractory AML or higher risk myelodysplastic syndromes (MDS). Information about eligibility criteria can be found here; for contacts and locations, visit here.

The orphan drug designation offers Precigen support for its clinical trials of PRGN-3006. It also provides a waiver from the FDA’s prescription fees and seven years of marketing exclusivity in the U.S. should the therapy be approved for AML.

If PRGN-3006 is also later granted priority review or a breakthrough therapy designation, the company then would be entitled to a faster regulatory process.

“This regulatory designation underscores the critical medical need for new therapies to treat AML patients. AML is a progressive, debilitating and often fatal disease with limited treatment options,” Helen Sabzevari, PhD, president and CEO of Precigen, said in a press release.

“As the first regulatory designation for our proprietary UltraCAR-T platform, this orphan drug designation helps to advance the PRGN-3006 investigational therapy and provides important incentives and support to deliver this medicine as rapidly as possible,” she continued.

PRGN-3006 is a chimeric antigen receptor (CAR) T-cell therapy, a type of immunotherapy that combines cell therapy and genetic engineering.

It consists of isolating T-cells — cells of the immune system with the power to kill tumor cells — from the patient’s blood. In the laboratory, these cells are genetically modified to express a surface receptor, called a chimeric antigen receptor (CAR), that gives T-cells the ability to recognize and attack cancer cells.

Usually, this is followed by several rounds of cell division in the lab to expand the population of modified T-cells, which are then reinfused back into the patient’s blood.

PRGN-3006, however, employs Precigen’s UltraCAR-T platform, a new methodology that shortens manufacturing time from weeks to days, reducing the time patients have to wait for the treatment to be completed. Compared with conventional CAR T-cell therapies, this technology has the potential to be safer and to prolong the tumor-killing capacity of immune cells.

UltraCAR-T uses a non-viral gene delivery system that streamlines manufacturing and ensures high cell survival. This eliminates the need for cell propagation in the lab, allowing the infusion of T-cells just one day after they have been genetically modified. According to the Precigen website, that leads to “dramatically reducing” wait times for patients.

Using this technology, T-cells are engineered to express three different molecules. One is a chimeric receptor targeting CD33, which is a marker of leukemia cells in 85-90% of AML patients. Another is a membrane bound IL-15, added to avoid T-cell “exhaustion,” which promotes cell expansion inside the body, and prolongs their tumor-killing ability. The third molecule is a “kill switch” for better precision and control of cancer cell targeting, which improves the therapy’s safety profile.

Preclinical data, recently presented at the American Society of Hematology 2019 Annual Meeting, demonstrated PRGN-3006’s specific and prolonged activity against AML cells, as well as its ability to reduce tumor burden and prolong survival in mice with human AML tumors. The study investigators believe this data provides “a strong rationale” to evaluate PRGN-3006 in a clinical trial.

The first human Phase 1 clinical trial of PRGN-3006, currently ongoing in collaboration with the Moffitt Cancer Center, will determine the safety and optimal dose of PRGN-3006.

Two different regimens will be tested — one with and one without a lymphodepletion treatment. That treatment eliminates the T-cells remaining in the patient’s body prior to the infusion of PRGN-3006.

For each group, there will first be a dose-escalation part to find the maximum tolerated dose — the highest dose with acceptable side effects — followed by an expansion phase using the dose previously identified.

Enrollment has already completed for the group of patients assigned the first dose of PRGN-3006 without lymphodepletion. Initial data is expected in the second half of 2020.