NEW YORK – Silverback Therapeutics is shutting down its targeted oncology programs and cutting its workforce by 27 percent as it refocuses resources on developing chronic hepatitis B drugs and its ImmunoTAC drug discovery platform.
In reporting its 2021 financial results on Thursday, the Seattle-based company said it would discontinue developing two antibody-drug conjugates, SBT6050 and SBT6290, in biomarker-informed cancer indications.
In September 2021, Silverback reported results from a Phase I/Ib study of SBT6050 in HER2-expressing solid tumors. At the time, Silverback said that SBT6050 was generally well-tolerated with a "manageable" adverse event profile. However, the company this week said that while some patients had a dose-related response in that study, it decided to stop further development "based on limited monotherapy anti-tumor activity and cytokine-related adverse events" that would limit the acceptable dose of SBT6050 that patients could receive in combination with Merck's checkpoint inhibitor Keytruda (pembrolizumab).
SBT6050 comprises a small molecule toll-like receptor 8 (TLR8) agonist conjugated to a HER2-directed monoclonal antibody. TLR8 is expressed in myeloid cells, which are present in tumors. The TLR8 agonist is designed to target those cells, theoretically activating human myeloid cells expressing HER2 and triggering the innate immune system to drive anti-tumor responses.
The other drug Silverback has abandoned, SBT6290, uses the same linker payload conjugated to a Nectin4 antibody. Nectin4 is a cell surface adhesion molecule overexpressed in many solid tumors including urothelial, triple-negative breast, squamous cell head and neck, and non-small cell lung cancers. In 2021, Silverback presented preclinical data at the American Association for Cancer Research's annual meeting demonstrating that SBT6290 activates human myeloid cells and has single-agent anti-tumor activity in mice.
Silverback, having expected SBT6290 to show a clinical profile similar to SBT6050, discontinued that program, also.
"Upon comprehensive review of our clinical and preclinical data for our TLR8 oncology programs, we have made the decision to discontinue the development of SBT6050 and SBT6290 and focus our resources on SBT8230 for chronic HBV as well as our ImmunoTAC discovery programs," Silverback CEO Laura Shawver said in a statement. "Over the course of the next few days and weeks, we are restructuring our workforce and allocating resources around our new strategic priorities."
The firm will continue early-stage discovery research on antigen targets, novel linker technologies, and small molecule payloads that expand uses of its ImmunoTAC platform.
Silverback ended 2021 reporting a net loss of $89.5 million compared to a net loss of $32.9 million in 2020. As of Dec. 31, Silverback reported cash, cash equivalents, restricted cash, and investments of $319.1 million. The company said its strategic prioritization will provide sufficient cash runway until the second half of 2026.