Duke Street Bio Announces First Patient Dosed in Phase I Trial with DSB2455, a Next Generation PARP1 Selective Inhibitor for the Treatment of Solid Tumours

3 December 2024 -- London, UK -- Duke Street Bio Ltd, a precision medicine biotech developing next-generation small molecule cancer therapies, is pleased to announce that the first patient has been dosed in a Phase I trial evaluating the highly selective PARP1 inhibitor, DSB2455, in patients with solid tumours. DSB2455 is a potentially best-in-class, potent CNS penetrant PARP1 inhibitor with profound selectivity over the closely related enzyme PARP2.

The Phase Ia/Ib trial is a multi-centre adaptively designed dose escalation study with expansion cohorts to assess the safety, tolerability, and activity of DSB2455 as monotherapy or in combination with anti-cancer agents in participants with advanced malignancies. First-generation non-selective PARP1/2 inhibitors have provided significant therapeutic benefit to patients whose tumours exhibit homologous repair (HR) deficiencies including BRCA mutations. However, their use has been associated with haematological toxicities that have restricted their application, particularly in combination with standard-of-care chemotherapy.

"Given that PARP2 is considered to drive haematoxicity, we believe that DSB2455 exhibits the optimal potency and selectivity profile to enhance efficacy and safety and may offer the potential to enable combination approaches with chemotherapy and radiotherapy" said Dónal Landers, M.D., Ph.D., Chief Medical Officer at Duke Street Bio Ltd.

About Duke Street Bio Ltd
Duke Street Bio is a precision medicine biotech focused on exploiting tumour genetic vulnerabilities by developing the next generation of molecules targeting DNA Damage Repair (DDR) deficiencies in cancer. The company was founded by a highly experienced leadership team with a track record of developing best-in-class therapeutics and supported by a world class SAB. The company’s lead program, DSB2455, is a potentially best-in-class, potent CNS penetrant PARP1 inhibitor with profound selectivity over the closely related enzyme PARP2. For more information, please visit www.dukestreetbio.com.