Bicycle Therapeutics is letting more air out of its operations, with plans to deflate its employee count by about 30% and shelve its lead anti-cancer drug conjugate.
The reprioritization is meant to cut yearly operating costs by around 50%, Bicycle announced in its 2025 financial results on March 17. That should extend the company’s cash runway by an extra two years to 2030.
After the layoffs, the company will employ around 200 people, a Bicycle spokesperson confirmed to Fierce Biotech. The biotech employed 288 people as of Dec. 31, 2025, according to its most recent annual report (PDF).
Alongside the exiting employees, Bicycle is putting the brakes on two trials of its Nectin-4-targeting drug conjugate zelenectide. The phase 1/2 Duravelo-3 trial in breast cancer and the phase 1/2 Duravelo-4 trial in non-small cell lung cancer are both being discontinued, according to the release, though already enrolled patients will be able to ride out their treatment course.
These halted trials come as zelenectide bumps against a regulatory roadblock in a different indication. Regulators have told Bicycle that the open-label phase 2/3 Duravelo-2 trial is no longer considered appropriate to support approval in advanced or metastatic urothelial cancer (mUC), the biotech said.
As a result, Bicycle is now working to convert the open-label study into a randomized phase 2 trial, but will then stop further advancement, CEO Kevin Lee, Ph.D., said in the release.
“We have reached the difficult decision to deprioritize this program for internal development at this time,” Lee said. “Once we have these randomized phase 2 data in hand, we will determine the most appropriate path for zelenectide.”
Related
The apparent push for Bicycle to conduct a randomized study fits with the modus operandi of the FDA’s recent demands for randomized, placebo-controlled trials, even in rare diseases with small patient populations. The priority aligns with comments made by the top biologics regulator, Vinay Prasad, M.D., who is set to depart the agency at the end of April.
Accordingly, the FDA’s recent rejections have often gone against past guidance the agency provided to biotechs before Trump’s administration overhauled the agency last year.
In September 2023, Bicycle announced that it had aligned with the FDA on the design of Duravelo-2 as a registrational trial, meaning it could potentially support a drug approval. The trial then kicked off in early 2024.
“Preliminary regulatory feedback is aligned that zelenectide has a potentially improved tolerability profile compared to existing treatments and regulators have proposed a number of innovative options for continued development,” the Bicycle spokesperson explained.
“From the feedback we have received it is clear that we need more discussions to determine the optimal way to develop zelenectide and that these discussions would be further aided by reviewing additional data” from the Duravelo-2 trial, the spokesperson added.
In lieu of zelenectide, Bicycle will instead be hitting the road with the rest of its drug conjugate pipeline, with EphA2-targeting BT5528 leading the way. BT5528 is currently being trialed in an open-label, single-arm phase 2 study for previously treated metastatic pancreatic ductal adenocarcinoma.
Bicycle’s new layoff round comes not long after a 25% workforce reduction last August, which itself followed—but was reportedly unrelated to—Genentech terminating a partnership with the biotech.
Editor’s note: This story was updated at 2:30 p.m. ET with comment from Bicycle.
