Precigen UltraCAR-T Technology Flexes its Muscles at ASH Meeting

Since taking over the reins of Germantown-based Precigen in 2020, Chief Executive Officer Helen Sabzevari has been touting the benefits of the company’s UltraCAR-T cell therapy platform as well as its prospects as a game-changing technology for personalized cancer therapies.

At the American Society of Hematology meeting earlier this month, Precigen presented positive interim data from an ongoing Phase 1/2b clinical study of PRGN-3006 UltraCAR-T in patients who have been diagnosed with relapsed or refractory (r/r) acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (MDS). The interim study data showed what the trial investigators are calling “excellent, dose-dependent expansion.”

The Phase 1/2b clinical study is designed to include two phases, an initial dose-escalation phase followed by a dose-expansion phase. The study will assess the safety of the cell therapy, as well as determine the maximum tolerated dose of PRGN-3006 delivered via intravenous (IV) infusion without lymphodepletion (Cohort 1) or with lymphodepletion (Cohort 2). The study is also evaluating in vivo persistence and anti-tumor activity of PRGN-3006.

At ASH, the Precigen investigators said that blood and bone marrow samples taken more than three months after a single infusion of the cell therapy found the UltraCAR-T cells remained in the patients. That means the drug is remaining within the patient longer in order to produce what Precigen hopes is a sustainable impact on the tumor.  

The presentation at ASH included data from 15 patients with r/r AML who were part of the non-lymphodepletion and lymphodepletion cohorts of the study. Patients in the study had been heavily pre-treated with four and three regimens in the non-lymphodepletion and the lymphodepletion cohorts, respectively. Of those patients, Precigen noted that 33% and 50% had failed prior allogeneic hematopoietic stem cell transplant in the non-lymphodepletion and the lymphodepletion cohorts, respectively.

David A. Sallman, a hematologist with the Moffitt Cancer Center in Florida and lead investigator of the PRGN-3006 clinical study, said the interim data showed promise after a single infusion. He said there was an overall response rate of 50% in patients in the lymphodepletion cohort who were treated with two of the lowest dosing levels. That data is “highly encouraging,” Sallman said and added that the “specifics of the responding patients suggest the potential for PRGN-3006 as a bridge to allo-HSCT, which is a very important potential treatment pathway for these patients.”

PRGN-3006 is a multigenic autologous CAR-T that simultaneously expresses a CAR that targets CD33 and membrane-bound IL-15, as well as a “kill switch” designed to conditionally eliminate CAR-T cells in order to improve the safety profile.

PRGN-3006 UltraCAR-T has been granted Orphan Drug Designation in patients with AML by the U.S. Food and Drug Administration.

Based on the interim data in both cohorts, Precigen CEO Sabzevari said they believe that the UltraCAR-T cells have the potential to improve outcomes for cancer patients.

“We are excited by these interim data, which clearly highlight the extraordinary potential and flexibility of the UltraCAR-T platform to deliver precision medicine to patients at any time, at any place and as many times as needed,” Sabzevari said in a statement.

CAR-T cell therapies are being pursued by multiple companies, but Sabzevari believes that Precigen’s UltraCAR-T technology is a next-generation approach that could simultaneously impact different types of genetic expressions on cancer cells, both hematological and solid tumors. In a previous interview with this reporter, Sabzevari said the UltraCAR-T immunotherapies can be developed with fewer toxicity issues and manufactured at a lower cost than currently available CAR-T treatments.

Precigen has advanced the UltraCAR-T platform to address the inhibitory tumor microenvironment by incorporating a novel mechanism for intrinsic checkpoint blockade without the need for complex and expensive gene-editing techniques. Sabzevaris noted that Precigen has the most differentiated platform in cell and gene therapy compared to other companies in the space. That differentiation could play a significant role in treating different mutations associated with various cancers.

UltraCAR-T investigational therapies are manufactured via Precigen’s overnight manufacturing process using the proprietary UltraPorator electroporation system and administered to patients only one day following gene transfer. The overnight UltraCAR-T manufacturing process does not use viral vectors and does not require ex vivo activation and expansion of T cells, potentially addressing major limitations of current T cell therapies.

While CAR-T therapies are not yet considered front-line defenses in cancer, Sabzevari predicted that cell and gene therapies will eventually move to first-line options due to the advances made in the field, similar to those made with checkpoint inhibitors.