Silverback Therapeutics is working on a new kind of antibody-drug conjugate (ADC): one that targets the immune response to cancer rather than attacking tumor cells themselves. And it’s just raised $78.5 million to bankroll its pipeline.
The company’s work is based on its ImmunoTAC platform, which attaches antibodies to small molecules that adjust the immune system instead of cytotoxic, or cell-killing, agents. The approach allows Silverback to target pathways that have previously been out of reach for small molecules due to their side effects.
“There are a number of pathways known to undergird the pathophysiology of various disease. But due to systemic toxicity associated with administering small molecules—and in some cases, antibodies, against those pathways—there hasn’t been a way to advance a therapy that appropriately targets or covers those pathways,” Silverback Chief Scientific Officer Valerie Odegard, Ph.D., told FierceBiotech.
The funding will push Silverback’s lead candidate into the clinic later this year. The Seattle-based company will test the treatment, SBT6050, an ADC that targets TLR8, in tumors that express the HER2 gene. The antibody makes sure the payload is delivered only to the HER2-expressing cancer cells, while the TLR8 agonist activates immune cells called myeloid cells to attack the tumor and “reprogram” the tumor microenvironment.
It’s an improvement on previous efforts with TLR8 agonists, which have been delivered systemically and lead to side effects that limit the amount of drug a patient can take, Odegard said.
SBT6050 isn't the first ADC to target HER2-positive cancers—after all, Genentech's Kadcyla has been available for years, getting its first approval for late-stage, HER2-positive breast cancer in 2013. But there is no standard of care for patients who relapse after receiving Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla.
AstraZeneca and Daiichi Sankyo are looking to unseat Kadcyla with their own ADC, Enhertu, which scored an FDA nod last December. But it has a less than perfect safety profile, with nearly all (99%) of the clinical trial patients experiencing side effects, including interstitial lung disease, for which the drug has a boxed warning.
Silverback's funding, drawn from the likes of U.S. Venture Partners, OrbiMed Advisors, Bristol Myers Squibb and Nextech Invest, will also propel a suite of preclinical-stage programs.
“We do anticipate being able to bring our second program into the clinic using this series B financing, while progressing our earlier programs toward the development candidate stage,” said Silverback CEO Peter Thompson, M.D. The company isn’t ready to spill which cancer types or targets those programs are aimed at but will divulge more over the course of the year. The company also plans to add to its 40-person team as it ushers its assets toward and into the clinic.