ESMO: Zentalis already dreaming of launch for WEE1 inhibitor after ‘great result’ in early-stage test

Biotech ESMO: Zentalis already dreaming of launch for WEE1 inhibitor after ‘great result’ in early-stage test By James Waldron Oct 23, 2026 10:15am ESMO 2026 Zentalis Pharmaceuticals ovarian cancer Oncology Zentalis Pharmaceuticals has pointed to the first overall survival (OS) analysis for azenosertib as proof that the WEE1 inhibitor can offer a convenient oral treatment for a tricky type of cancer. The slice of data comes from a phase 1b portion of the Denali study of azenosertib in patients with platinum-resistant ovarian cancer (PROC). These patients had received between one and five prior lines of therapy, including Avastin, at a median of three previous treatments.

Zentalis split the patients between 48 individuals whose cancer was Cyclin E1-positive and the remaining 46 whose cancer tested negative for the protein. In an abstract published ahead of the European Society for Medical Oncology conference in Madrid, Zentalis disclosed that the Cyclin E1-positive cohort saw median OS of 15.9 months, while the negative group saw OS of 7.5 months. At the time, William Blair pointed to an OS north of 15 months as “extremely encouraging.” On Friday, Zentalis used its presentation at the conference to reveal that the objective response rate (ORR) for Cyclin E1-positive patients was 37.2%, with a median duration of response of 5.5 months.

“We think it’s a great result,” Zentalis CEO Julie Eastland told Fierce in an interview on the eve of the conference. “The response rate here is one of the highest that we've seen in all the trials that we've done with azenosertib in the PROC setting as monotherapy, and the duration of the response is right down the ballpark of where we'd like to see it—between five and six months,” the CEO said. “So we're happy with that outcome.” Zentalis’ Chief Medical Officer, Ingmar Bruns, M.D., pointed out that the global standard of care for these patients remains single-agent chemotherapy, which has response rates between 4% and 12%.

“So this is more than triple of that,” Bruns said. The company believes that azenosertib is “really competitive,” as it could offer similar benefits to recently approved regimens while being “essentially just a pill,” he added. The oral administration of the therapy means it's “a new modality for both patients and physicians in this setting,” Eastland agreed.

WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints to prevent replication of cells with damaged DNA. Cancer cells accumulate significant DNA damage by dividing rapidly. By inhibiting WEE1, azenosertib is meant to enable cancer cells to continue to accumulate DNA damage until they die.

“Think of [WEE1] as the traffic cop at the school guard crossing,” Eastland said. “[The cell is] going to stop and look and see if they can progress to the next block, and if not, they don't get to go to school. They don't get to divide and replicate.” On the safety front, treatment-related adverse events (TRAEs) led to dose interruption in 56.9% of patients, dose reductions for 43.1%, and discontinuation in 19.6% of patients.

A total of 21.6% of patients experienced a serious TRAE, according to Zentalis. The most common TRAEs graded 3 or above were fatigue, which affected 16% of patients, as well as thrombocytopenia, which impacted 12% of patients, and anemia and neutropenia, which each affected 11% of patients. TRAEs also included the death of two patients from neutropenic sepsis, which saw the drug briefly placed on hold by the FDA in 2024.

Discussing those deaths, Bruns said the trials of azenosertib have shown “a pretty low rate of hematological toxicities [and] neutropenia … especially if we compare it with single-agent chemotherapy and emerging therapies.” The biotech has already started the phase 2 portion of the Denali program, which will focus specifically on patients with Cyclin E1-positive PROC, with the aim of supporting a push to secure accelerated approval from the FDA. That part of the trial is due to read out in the first half of next year. In the meantime, the company has already started enrolling in a phase 3 study, dubbed Aspenova, with the aim of recruiting 420 patients.

Last year, the biotech laid off 40% of its employees to keep cash flowing to the azenosertib program. With a phase 3 trial already underway, Eastland told Fierce that the company already has its eyes on taking the drug to market and will be hunting for a suitable partner. “We’ve brought on a couple of hires,” the CEO told Fierce.

“We’re doing our pre-commercial planning right now.” “We’ll start working towards that as Denali reads out, and be ready to go, should we have an opportunity to launch in the U.S. in the near term,” she added. The most exciting areas of biopharma R&D is among the hot topics being discussed at Fierce Biotech's high-impact event in London next month.

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