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AZ showcases data for next-generation PARP inhibitor AZD5305

Early preclinical data presented at virtual American Association of Cancer Research meeting

AstraZeneca (AZ) has unveiled early data for its next-generation PARP1 selective inhibitor AZD5305 – a potential successor to its blockbuster PARP treatment Lynparza.

Late last year, AZ commenced a phase 1 study of the experimental oral PARP1 inhibitor as monotherapy or in combination with anti-cancer agents in patients with advanced solid malignancies.

PARP inhibitors work to prevent cancer cells from repairing, by blocking PARP enzymes which help to repair DNA damage in cells – also known as the DNA damage response (DDR) pathway.

Lynparza (olaparib) selectively inhibits PARP1/2 and is a successful targeted therapy within AZ’s roster, although the British drugmaker is now looking to improve the drug with its next-generation candidate.

“Our data at AACR reflect a robust early-stage pipeline, poised to deliver life-changing medicines to patients living with cancer. Data for AZD5305 will demonstrate how the next wave of DNA damage response medicines can build on the success of PARP inhibitors, potentially allowing patients to stay on treatment longer,”said Susan Galbraith, senior vice president and head of research and early development, oncology R&D at AZ.

“This innovative molecule is designed to optimise the therapeutic window of PARP inhibition, providing new opportunities for combination treatment with chemotherapy and targeted medicine,” she added.

With AZD5305, AZ is seeking to develop a new PARP inhibitor treatment that offers new benefits by improving Lynparza’s safety profile, which can often be accompanied with adverse side effects.

At the virtual American Association of Cancer Research (AACR) annual meeting, AZ revealed data showcasing the efficacy of AZD5305 as monotherapy and in combination with standard of care chemotherapy in in vivo preclinical models.

Also at AACR, Zentalis Pharmaceuticals announced early-stage data for its WEE1 inhibitor – ZN-c3 – in patients with advanced solid tumours.

The ongoing study found that Zn-c3 generated five partial responses (PR), with two confirmed PRs in ovarian cancer and colorectal cancer patients, as well as three unconfirmed PRs – one in non-small cell lung cancer and two in uterine serous carcinoma.

Like PARP inhibitors, the inhibition of WEE1 is focused on the DDR pathway. ZN-c3 is an oral inhibitor of WEE1 that is aiming to generate sufficient DNA damage in cancer cells, causing cell death and preventing tumour growth.

Article by
Lucy Parsons

12th April 2021

From: Research



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