Published: Apr 01, 2022
By Vanessa Doctor, RN
Silverback Therapeutics is halting its clinical oncology programs and letting go of about 27% of its workforce as part of a restructuring initiative that would leave it with more cash reserves.
The Seattle-based biopharmaceutical firm said it will discontinue development efforts for SBT6050 and SBT6290 — HER2-TLR8 and Nectin4-TLR8 ImmunoTAC conjugates for oncology — to focus on its programs for chronic hepatitis B virus (cHBV). The SBT6050 project was in the Phase I/IB stage but saw only limited anti-tumor activity and cytokine-linked adverse events, which limited the dose when used with pembrolizumab. SBT6290 was also observed to have a similar outcome as SBT6050, prompting the company to also discontinue the program.
The decision to restructure operations and focus on chronic HBV and ImmunoTAC discovery programs is expected to leave Silverback with enough cash reserves to tide it over until the second half of 2026.
SBT8230 — an ASGR1-TLR8 ImmunoTAC conjugate for chronic HBV — is designed to prompt anti-viral immune response by targeting TLR8 activation to the liver. ASGR1 is highly expressed in this organ. SBT8230 prods an
immune response by activating myeloid cells, which indirectly activate T cells and B cells. Exploratory studies in non-human primates demonstrate its potential to create durable responses and possibly seroconversion. These findings, which were presented at a conference in 2021, are what’s prompting Silverback to launch a Phase I-enabling toxicology study in the first quarter of 2022.
“Over the course of the next few days and weeks, we are restructuring our workforce and allocating resources around our new strategic priorities. It will be difficult to part with valued team members who have been so committed to the organization, and I’d like to thank each one of them for their valuable contributions towards our mission to develop the next generation of tissue targeted therapeutics,” commented Sliverback CEO Laura Shawver, Ph.D.
The company expects to complete the regulatory submission for Phase I trial plans in the fourth quarter of 2022 and begin the open enrollment process for the same in healthy volunteers by the first half of 2023.
“The comparative preclinical data between SBT6050 and SBT8230 suggest that the clinical safety, pharmacokinetic and pharmacodynamic profiles for SBT8230 will likely be different than those for SBT6050, given the significant differences in preclinical serum exposures and expected overall conjugate disposition for SBT8230 in patients due to its efficient liver targeting. We continue to advance SBT8230 and are on track to complete a Phase 1 regulatory submission,” added Dr. Valerie Odegard, president and chief scientific officer of Silverback, in the same statement.
The restructuring plans were revealed alongside Silverback’s financial report for the fourth quarter and the year to December 31, 2021. The firm posted a $23.5 million net loss in Q4 and an $89.5 million net loss for the financial year. This was partly affected by high research and development expenses related to SBT6050 and SBT6290 (and some costs related to SBT8230) at $15.9 million for Q4 and $61.5 million in the year, from only $8.8 million and $24.6 million in the same periods in 2020. At the close of 2021, Silverback recorded $319.1 million in cash, cash equivalents, restricted cash and investments from $386.6 million the year before.