AstraZeneca shares first clinical data for TeneoTwo bispecific T cell engager

SAN DIEGO — AstraZeneca is intensifying its efforts in the field of bispecific T cell engagers with a focus on a promising new treatment. The company recently revealed initial Phase 1 data for AZD0486, their CD3xCD19 bispecific antibody, at the American Society of Hematology’s annual meeting. This new therapy is being evaluated for its effectiveness in treating various B cell malignancies.

AstraZeneca's study, which covers a variety of blood cancers, involved testing AZD0486 across four different dose levels. The results show significant progress, particularly in patients with follicular lymphoma and diffuse large B cell lymphoma (DLBCL). Among 27 follicular lymphoma patients who received one of the three highest doses, an impressive 96% achieved an objective response rate, with 85% reaching a complete response. Notably, 17 out of 19 patients at the two middle dose levels reached an undetectable minimal residual disease stage within 12 weeks, a milestone that the FDA is increasingly considering in other blood cancers.

In the case of DLBCL, which is notoriously more difficult to treat, the responses were less pronounced. At the dose proposed for further studies, 47% of patients (9 out of 19) exhibited a response, and 42% (8 out of 19) achieved a complete response. AstraZeneca plans to present more detailed DLBCL results.

A notable aspect of the data is the positive response seen in patients who had previously received CAR-T or anti-CD20 therapies. Of the 14 patients who progressed post-CAR-T at the target dose level, 36% showed an objective response, and 29% achieved a complete response. Susan Galbraith, AstraZeneca’s executive VP for oncology R&D, highlighted the significant challenge faced by patients whose cancers advance after CAR-T therapy, noting that bispecifics are emerging as a potential new treatment option for them.

Galbraith expressed optimism about the potential of AZD0486, not only as a treatment for late-stage patients but also for its efficacy in early treatment lines. She emphasized the need for further data but remained enthusiastic about the market potential.

AZD0486 is a product of AstraZeneca’s acquisition of TeneoTwo in 2022 for up to $1.27 billion, including milestone payments. TeneoTwo originated from Teneobio, which Amgen acquired in 2021 for $900 million upfront and an additional $1.6 billion in milestones. The only other approved CD3xCD19 bispecific antibody is Amgen’s Blincyto, initially approved in 2014 and subsequently gaining several other approvals for acute lymphoblastic leukemia (ALL). Blincyto generated $861 million in global sales in 2023.

Galbraith pointed out that the scarcity of similar drugs has provided AstraZeneca with an opportunity to develop AZD0486 to optimally exploit the market. She also mentioned the untapped potential for combination therapies, particularly for DLBCL, which could be explored in future clinical settings.

Other pharmaceutical companies have also shown interest in this area. Recently, several CD19 bispecific deals have been announced. In August, Merck invested $700 million upfront in Curon Biopharmaceutical’s CD3xCD19 compound. In October, GSK spent $300 million upfront for a bispecific from Chimagen Biosciences, aimed at treating autoimmune diseases.

Galbraith believes that AZD0486 could surpass existing treatments in efficacy. She noted that the exposure levels achievable with AZD0486 could potentially exceed those of Blincyto, suggesting a more effective CD19 bispecific option for patients with ALL. Galbraith remains encouraged by the emerging profile of AZD0486 and its promising potential.