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Investors Back Seattle-Based Startup’s Novel Immuno-Oncology Program Targeting Solid Tumors
By Ruchi Jhonsa, Ph.D.
Investors certainly have a lot of hope from Silverback’s experimental ADC drug, which has just been granted third funding since its inception in 2016. Silverback Therapeutics, a privately-held biopharmaceutical company, announced the closing of $85 million Series C funding on 23rd September. The company is working on antibody-drug conjugates, which, unlike other ADCs, are designed to stimulate the body’s immune response to cancer. These ADCs are churned by the company’s proprietary platform called ImmunoTAC, which attach antibodies to small molecules that trigger the innate immunity instead of killing the cancer cells.
Solid tumors, including tumors that don’t respond to immune-checkpoint therapies, are flooded with myeloid cells. These cells can initiate or suppress an antitumor immune response; however, in the presence of certain ligands such as TLR, it is possible to tip the immune response against the cancer cells. Silverback’s lead program, SBT6050, has been designed to stimulate the myeloid cells against cancer. It is a TLR8 conjugated HER2 antibody that targets cancers overexpressing HER2 protein and delivers TLR8 ligand in the tumor microenvironment where it can turn on the antitumor myeloid activity. The advantage of this drug is that it prevents any off-target effects as high expression of HER2 in tumors pulls ADC away from organs, and robust expression of TLR8 receptor in tumor prevents off-target activation of the immune system.
Silverback intends to use these proceeds to support its lead clinical programs as well as push its other ImmunoTAC programs, including an ADC aimed at Nectin-4, and undisclosed programs in cancer, virology, and fibrosis.
“Silverback has made impressive progress developing a differentiated approach to immuno-oncology,” said Scott Platshon, principal, EcoR1 Capital. “Broad activation of innate immune cells has been difficult to achieve due to systemic toxicities. Silverback has persisted in understanding how to deliver TLR8 agonists with a good preclinical safety and tolerability profile, and we are excited to lead an investment round that will help Silverback investigate the translatability of these findings to patients with HER2-expressing solid tumors.”
HER2 has been an attractive target for many cancer therapies in the past. Herceptin was the first HER-2 targeted therapy to get approval for the treatment of breast cancer and has been in the market for 20 years now. The drug is a monoclonal antibody against the HER2 receptor. While Herceptin has been effective in cancer treatment, several companies have combined the drug with small inhibitor molecules to produce high-efficiency ADC. Daiichi Sankyo and AstraZeneca’s Enhertu and Roche’s Kadcyla are few in the ADC category to have dominated the market for several years.
While it is clear that with the third round of funding, investors are impressed with the silverback’s ADC drug, it is unclear how the drug would fare in clinical trials. Although the drug has solid preclinical data and is currently in the phase 1 safety trial in patients with HER2-expressing solid tumors, it will be years before one will know its true potential.
Currently, the investors have their eyes on Silverback’s HER-2 targeted ADC, but this is not the only drug the company is developing. It is also working on Nectin-4 targeted ADC that will target solid tumors, including urothelial, breast, gastric, and lung carcinomas. So far, the only available Nectin-4 ADC is Seattle Genetics’ Padcev, which got the USFDA approval last year. This means tough competition for the Silverback’s drug, which has not even got into clinical trials. Nevertheless, if the drug works, it can certainly rule the market with its unique mechanism to augment immune response and can complement existing checkpoint immunotherapies that are limited in their efficacy by the tumor microenvironment.
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