Dive Brief:

• Bicycle Therapeutics said Tuesday that it will lay off 30% of its workers and “deprioritize” an experimental antibody-drug conjugate that has been seen as a possible threat to Pfizer’s bladder cancer drug Padcev.
• The decision was driven by discussions with the Food and Drug Administration and other regulators about the approval path for the therapy, known as zelenectide pevedotin. While regulators agreed with Bicycle on the optimal dosing strategy for the drug, they aren’t convinced that the results from an ongoing Phase 2 trial called Duravelo-2 will be sufficient to support an accelerated approval in metastatic bladder cancer.
• Bicycle said the trial is advancing toward a randomization phase and its executive team will determine the next steps forward after reviewing the results. In the meantime, the company will shift its focus to a second ADC in testing against pancreatic cancer and other solid tumors, as well as radiopharmaceuticals in early-stage development.

Dive Insight:

Bicycle has been aiming to show that zelenectide might eventually prove superior to Padcev.

But that’s a tall order, as Padcev — which Pfizer gained through its $43 billion buyout of Seagen — is well-entrenched in bladder cancer care. It recorded sales of more than $1.9 billion in 2025, and use has rapidly expanded from late-stage disease to earlier lines of care thanks to benefits observed when paired with Merck & Co.’s Keytruda.

Zelenectide and Padcev are ADCs that latch onto a tumor protein called Nectin-4 and release a cancer-killing toxin. But Bicycle has been hoping that its drug might match Padcev’s effectiveness with a cleaner safety profile, as Pfizer’s therapy is associated with neuropathy and certain skin toxicities. 

Still, Bicycle shares have lost much of their value over the last year, rendering the company worth less than its cash reserves, on “less confidence” in the therapy’s ability to stand out, wrote Jefferies analyst Maury Raycroft, last month. 

Bicycle, for its part, said Tuesday that its drug had produced response rates in its Phase 2 trial that were “comparable” to what’s been seen with standard therapies while offering a “differentiated” safety profile. When combined with Keytruda, the drug stimulated a response at 27 weeks in 58% of people with metastatic disease who have received one or fewer treatment lines. By comparison, Padcev plus Keytruda achieved a response rate of nearly 68%.

Yet while those figures were “broadly similar,” zelenectide’s results were “not competitive in our view, particularly given an unclear regulatory path where Padcev may be a required comparator,” wrote TD Securities analyst Tara Bancroft, in a note to clients.

With the decision to downgrade work on zelenectide and lay off workers, Bicycle said it will reduce operating expenses by about 50% and be able to fund operations through 2030. The company had $628 million in cash at the end of 2025.

Regulatory filings show that Bicycle had 288 employees as of Dec. 31, meaning around 86 people will be laid off.