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AACR 2024 preview – more companies pile into popular mechanisms

Most attention at the upcoming AACR meeting might be on clinical-stage projects, but several preclinical assets could also be worth watching, given their activity against hot targets. A case in point is Nectin-4, where Pfizer/Astellas’s ADC Padcev has set the pace, with plenty of others following. AACR abstracts reveal several preclinical ADCs, as well as a Nectin-4-targeted γδ cell therapy from Century Therapeutics. KRAS inhibition is another hot area, and AACR will see preclinical data on various G12D-selective projects, while multi-KRAS inhibitors are also set to feature, including Boehringer’s BI 3706674 and Quanta's "G12V-preferring" QTX3544. The pan-KRAS field is led by Revolution Medicines, but there is also plenty of early-stage interest; the G12D-selective field is getting increasingly crowded, and recently saw Jazz pick up a preclinical candidate from Redx. And, in an area that has seen a resurgence of late, Zymeworks has just unveiled a trispecific antibody targeting DLL3, CD3 and CD28. DLL3 blockade has come back into vogue after Amgen produced promising data in the phase 2 Dellphi-301 trial with its bispecific T-cell engager tarlatamab at last year’s ESMO meeting; that project has a PDUFA date of 12 June in advanced small-cell lung cancer.

 

Notable preclinical abstracts at AACR 2024

ProjectCompanyMechanismAbstractSession typeNote
ADRX-0706Adcentrx TherapeuticsAnti-Nectin-4 ADC1891PosterIn ph1 in solid tumours
LY4052031LillyAnti-Nectin-4 ADC1872PosterIND expected 2024
IPH45Innate PharmaAnti-Nectin-4 ADC6582OralPh1 to start 2024
CNTY-107Century TherapeuticsNectin-4 targeted Car γδ T-cell therapy1916PosterIND expected 2025
TSN1611Tyligand BioscienceKRAS G12D inhibitor3315PosterPh1/2 to start H1 2024
LY3962673LillyKRAS G12D inhibitor3316PosterPh1 to start 2024
BI 3706674Boehringer IngelheimMulti-KRAS inhibitor3317PosterIn ph1 in stomach/oesophageal cancers
GFH375 (VS-7375)Verastem/ GenFleetKRAS G12D (ON/OFF) inhibitor3318PosterChina ph1 to start H2 2024
QTX3544Quanta TherapeuticsG12V-preferring multi-KRAS inhibitorLB163Late-breaking poster
UnnamedZymeworksAnti-DLL3/CD3/CD28 trispecific MAvb6716Poster

Source: AACR 2024. This story has been updated to include QTX3544.

The 2024 AACR meeting takes place in San Diego on 5-10 April.