Shawver takes the wheel at I-O biotech Silverback Therapeutics

After Sanofi snapped up Synthorx for $2.5 billion in January, the latter’s CEO, Laura Shawver, Ph.D., was out of a job. She wasted no time scoping out her next gig, eventually reuniting with an old colleague and landing at the helm of Silverback Therapeutics, a biotech working on a new kind of antibody-drug conjugate (ADC).

“I am first and foremost a scientist—my curiosity of the unknown is what drives me. There was never a question I would be joining another biotech,” Shawver told FierceBiotech.

The real question, then, was where she’d end up. After talking with lots of people about interesting science and compelling business opportunities, Shawver fell in with Peter Thompson, M.D., the OrbiMed partner who co-founded Silverback and Cleave BioSciences—the first biotech Shawver led—and who also invested in Cleave and backed Synthorx’s series C round in 2018.

“We’ve been sharing stories for a long, long time and we’re like-minded in that we oftentimes see the gaps and ask ourselves the question: How can we fill those gaps?” Shawver said. “That’s why he started Silverback.”

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Silverback’s pipeline is based on its ImmunoTAC platform, which combines antibodies with small molecules that adjust the immune response rather than kill cancer cells. It allows Silverback to get at disease-driving pathways that have been previously out of reach for small molecules because of 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 last month, when the company closed its $78.5 million series B.

It's one way to reach patients who have not benefited from advances in cancer treatment, from checkpoint inhibitors to T-cell therapies. Although these medicines have transformed treatments for certain types of cancer, it’s still a minority of patients, Shawver said.

“There is this whole group out there that doesn’t have any T cells—what do we do for them?” she said.

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Instead of T cells, Silverback is zeroing in on immune cells called myeloid cells. Its lead program is SBT-6050, 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 the myeloid cells to attack the tumor and “reprogram” the tumor microenvironment. 

The series B will push SBT-6050, along with a second program, into clinical trials. It will also support earlier-stage work, in which Silverback will be “mixing and matching payloads with antibodies” in the areas of fibrosis and virology as well as oncology.