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Bispecifics and allogeneics steal the spotlight from autologous CAR Ts

At ASH19, it’s all about how to replace first-gen CAR Ts with something better

Standing out at this year's ASH meeting is a pair of growing threats to first-generation CAR T cell therapies: bispecific antibodies and allogeneic cell therapies. Gone are the days when autologous CAR Ts were the meeting’s golden child. Now the task is to show what can improve on CAR Ts, and to demonstrate ways of fixing their flaws, or advancing competing technologies that can leapfrog them.

BioCentury’s survey of the 4,780 abstracts from this year’s American Society of Hematology (ASH) annual meeting, which takes place Dec. 7-10 in Orlando, identifies 42 new and emerging targets and 19 compounds with first-in-human data (see “Emerging Immuno-Oncology Mechanisms at ASH2019”).

The survey uses a machine-learning algorithm to detect specific context-relevant terms followed by manual validation, and is coupled with analysis of the trends that emerge to present a picture of the state of preclinical and clinical research in blood cancers and other hematological disorders.

The strong showing of bispecific research continues the thread from this year’s American Society of Clinical Oncology (ASCO) meeting, where abstracts focused on bispecifics showed the biggest year-on-year increase of all modalities (see “ASCO 2019 Abstracts Show Solid Tumor Race Heating”).

Whereas ASCO highlighted a clinical showdown between bispecifics and CAR Ts, demonstrating bispecifics making inroads into solid tumors, ASH 2019 features several preclinical innovations to bispecific constructs that could help them compete with CAR Ts on efficacy and broaden their range of indications. ASH 2019 also has the next readouts in the BCMA story--a target in sights of CAR T cell and bispecific antibody developers that is touted as the next, best hope for expanding immunotherapy to tackle multiple myeloma (MM).

The last two years at ASH have seen a jump in activity in bispecifics, with abstract numbers more than doubling since BioCentury started analyzing the annual meeting in 2016 (see Figure: “Upward Momentum for Bispecifics at ASH”).


Figure: Upward momentum for bispecifics at ASH

CAR T cells remain one of the most heavily-studied modalities at the American Society of Hematology (ASH) meeting this year, but competing bispecific antibodies are also on an upward trend. Since BioCentury started analyzing the meeting in 2016, the number of abstracts covering bispecific antibodies has more than doubled, increasing from 27 in 2016 to 69 in 2019. Although the number of bispecific abstracts remained relatively flat this year, more targets are represented in this year's crop, including targets that aren't being pursued by CAR Ts in development.

Bispecific antibodies aren't limited to T cell-engaging antibodies for cancer. Each year, at least 7% of the bispecific antibodies are for other hematology indications, and most of those are bispecifics

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