In the four years that Silverback Therapeutics has been developing cancer immunotherapies that avoid dangerous side effects, the biotech has mostly kept a low profile. Now the company has $78.5 million in cash to advance that research, and it’s starting to open up about its work.
The Series B round of funding brings the Seattle-based biotech’s total venture capital haul to about $125 million. Silverback says this new money will allow it to move its lead drug candidate into the clinic, as well as further advance its preclinical pipeline.
The company plans to ask the FDA for permission to start human testing of its most advanced therapeutic candidate, SBT6050, later this year. The compound, a drug conjugate that combines an antibody and an immune system modulator, targets solid tumors that express human epidermal growth factor, receptor 2, or HER2.
Overexpression of HER2 is most commonly associated with a subtype of breast cancer, which is known to be especially aggressive and less responsive to hormone therapy, but Silverback CEO Peter Thompson says subsets of tumors in other areas—including the lung, stomach, and colon—also express the protein. That means HER2 can also be a target for drugs addressing cancers in those parts of the body.
Thompson said preclinical studies showed systemic delivery of SBT6050 was able to activate TLR8, a receptor expressed in myeloid cells, which spurred the myeloid cells to kill tumor cells itself and to reprogram the tumor microenvironment in a way that prompted T cells to attack.
Others have also looked to develop drugs that take advantage of the receptor to turn the immune system against the tumor cells.
“We initiated this program with a desire to identify a very potent agonist for myeloid cells, which are readily abundant in human tumors, and when they are appropriate activated, unleash a number of immunological mechanisms that ultimately kill tumor cells,” says Valerie Odegard, Silverback’s chief scientific officer (pictured). “The challenge has been really being able to target the myeloid cells in the tumor because of associated toxicities in the past with systemically administered TLR or myeloid cell agonists.”
Side effects of such investigational drugs have included cytokine release syndrome, which occurs when the immune system goes into overdrive and causes systemwide inflammation, as well as issues at the injection site for drugs administered subcutaneously and in the gastrointestinal tract for those given orally. Such toxicities occurred because the agonist acted on myeloid cells outside of the tumor environment, says Odegard. Silverback believes its drug conjugates will avoid those side effects by targeting a genetic marker, such as HER2, which in turn enables the therapy to precisely hone in on tumor tissue.
Odegard, who has been with Silverback since its early days, joined from Juno Therapeutics, another Seattle area cancer drug developer, where she served as vice president of research. Juno, which was advancing cell therapies, was acquired in 2018 by Celgene, which has since been swallowed up by Bristol Myers Squibb (NYSE: BMY).
Thompson, a venture partner at OrbiMed Advisors and Silverback co-founder, has served as the company’s CEO since its founding—except for a short stretch in 2018, when longtime Seattle Genetics (NASDAQ: SGEN) executive Eric Dobmeier held the role. Thompson returned as chief executive after Dobmeier decamped to Chinook Therapeutics, which came out of stealth last fall with plans to developing treatments for rare kidney diseases.
Silverback, with about 40 employees, has other experimental treatments, for oncology and fibrosis indications, in its preclinical pipeline that the Series B cash will help it advance, although Thompson and Odegard wouldn’t say much about those drugs.
US Venture Partners led the round. Earlier investors that participated include OrbiMed, Bristol Meyers Squibb (now-subsidiary Celgene was an early backer), and Alexandria Venture Investments. There were also new investors in the round, including Nextech Invest, Hunt Investment Group, Pontifax Venture Capital, Colt Ventures, and NS Investment.
As part of the deal USVP general partner Jonathan Root and Nextech partner Thilo Schroeder join Silverback’s board of directors.