Harnessing PHE885: Advancing CAR-T Therapy for Multiple Myeloma with a Rapid and Potent BCMA Targeting Approach

A novel treatment for multiple myeloma (MM) has been developed, focusing on a chimeric antigen receptor T cell (CAR-T) therapy that targets the B cell maturation antigen (BCMA). The therapy, named PHE885, is designed to address the limitations of current BCMA CAR-T treatments and to offer a more potent and enduring response. The development process involved a comprehensive screening of 17 CARs, leading to the selection of a fully human anti-BCMA single chain variable fragment (scFv) with high specificity and affinity.

The PHE885 CAR-T product is engineered with an extracellular scFv linked to the CD8α hinge and transmembrane domains, and includes CD137 (4-1BB) co-stimulatory and CD3ζ signaling domains. This construct was found to be superior in functional assays, demonstrating enhanced potency and the ability to maintain the stemness of T cells, which is crucial for a longer therapeutic response.

A key innovation in the development of PHE885 is the T-Charge™ manufacturing platform, which allows for a rapid production process of less than two days, avoiding the need for T cell expansion. This process results in CAR-T cells that retain a higher proportion of naive/stem cell memory T cells (Tscm), which are known for their engraftment and expansion capabilities.

In vitro and in vivo studies have shown that PHE885 secretes significantly more target-specific IL-2 and IFN-gamma compared to traditional manufacturing products. Moreover, in a mouse model of MM, PHE885 induced tumor regression at lower doses and demonstrated greater efficacy and cellular expansion than traditional products.

The enhanced potency and persistence of PHE885, attributed to its novel CAR construct and the T-Charge™ manufacturing process, have led to the initiation of a Phase 1 clinical trial (NCT04318327) for patients with relapsed/refractory MM. Initial findings from the trial's dose escalation phase will be presented, showcasing the potential of this innovative CAR-T therapy in treating MM.