Precigen Inc. (NASDAQ: PGEN) has presented positive preliminary data from the ongoing phase 1/1b clinical study of PRGN-3006 UltraCAR-T in refractory or relapsed acute myeloid leukemia and high-risk myelodysplastic syndromes patients at the 63rd Annual ASH Meeting and Exposition. Lead PRGN-3006 clinical trial investigator David Salliman delivered the oral presentation of the findings (abstract # 825). In addition, the company is evaluating PORGN-3006’s antitumor activity and in vivo durability in the study.
PRGN targets CD33 for enhanced in vivo multiplication
PRGN-3006 UltraCAR-T is a multigenic autologous CAR-T that expresses a CAR that precisely targets CD33, membrane-bound IL-15 for improved in vivo multiplication and persistence, and a kill switch that temporarily eliminates CAR-T cells for a better safety profile. On AML blasts, CD33 is overexpressed, whereas normal hematopoietic stem cells have lower expression levels. Most importantly, the US Food and Drug Administration has designated PRGN-3006 UltraCAR-T as an orphan drug for patients with AML.
Interestingly, PRGN3006’s tolerability profile was encouraging, and there were no neurotoxicity or dose-limiting toxicities in the study. Generally, subjects showed a low incidence of side effects after PRGN infusion, with the most common adverse events being anemia, cytokine release syndrome, and drop of lymphocyte count. In addition, peripheral blood samples analysis following PRGN-3006 infusion showed gene expression changes that were consistent with immune compartment function improvement for antitumor effect in responders.
Precigen to expand study into multicenter phase
The study is expected to move onto a multicentre expansion stage with a plan to assess the potential of repeated PRGN-3006 dosing.
Lead study investigator David Sallman commented, “The interim data for PRGN-3006 showed excellent, dose-dependent expansion and persistence of PRGN-3006 in peripheral blood and bone marrow following a single infusion, with detection of UltraCAR-T cells in blood more than 3 months post-infusion in the non-lymphodepletion and lymphodepletion cohorts. An ORR of 50% in patients treated at the two lowest dose levels in the lymphodepletion cohort is highly encouraging and 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.”
