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Boundless enthusiasm for CHK1

The clinical focus of Boundless Bio, which yesterday filed to go public, will ring some old bells. The group’s lead asset is BBI-355, a CHK1 inhibitor – a mechanism in which many big pharma names once had a hand, but which is now the preserve of just a few small biotechs. In recent years clinical-stage CHK1 inhibitors have been discontinued by Merck & Co, AstraZeneca and Roche, while Lilly’s two were sold to Esperas Pharma and Acrivon, where their development continues. The UK’s Sareum originated SRA737, which was licensed to Sierra Oncology before being returned to Sareum when Sierra was bought by GSK. Boundless targets extrachromosomal DNA, claiming that this is detected only in cancer cells, and says CHK1 manages its replication and transcription; blocking CHK1 thus causes synthetic lethality in tumour cells that rely on such DNA. Boundless's second clinical asset, which like BBI-355 appears to have been internally developed, is the RNR inhibitor BBI-825; the only other active RNR inhibitor, according to OncologyPipeline, is NCI/City of Hope’s COH29, after Taiho (Otsuka) discontinued TAS-1553 last year. Boundless raised $49m, $105m and $100m respectively in its series A, B and C rounds.

 

Selected clinical-stage CHK1 inhibitors

ProjectCompanyStatus
XCCS605BZhejiang MedicinePh2 trial in China
ESP-001/ LY2880070Esperas Pharma (ex Lilly)Ph1/2 in solid tumours
Prexasertib/ ACR-368*Acrivon (ex Lilly)Ph1/2 in ovarian, endometrial & urothelial cancers
SRA737Sareum (formerly licensed to Sierra & GSK), licensed to undisclosed private US biotech in Jan 2024Ph1/2 completed in 2020
BBI-355Boundless BioPh1 Potentiate trial in oncogene-amplified tumours
PEP07PharmaEngine Ph1 in AML/mantle cell lymphoma
BEBT-260Guangzhou BeBetterPh1 trial in China
MK-8776/ SCH 900776Merck & CoDiscontinued in ph2
GDC-0575/ RG7741Roche (ex Array)Discontinued in ph1
AZD7762*AstraZenecaDiscontinued in ph1

Note: *CHK1/2 inhibitor; all others are specific for CHK1. Source: OncologyPipeline.