Privately held Silverback Therapeutics Inc. continued its drive toward the clinic with an oversubscribed series B financing of $78.5 million to support its lead candidate, an anti-HER2 antibody conjugated to a TLR8 agonist for treating moderate or high HER2-expressing solid tumors.
The 4-year old company plans to file an IND for candidate SBT-6050 sometime this year and also begin its clinical study on the drug. The TLR8 agonists targeting the HER2-expressing tumors are designed to activate myeloid cells that would kill the cancer and reprogram the tumor. Preclinical data presented at the San Antonio Breast Cancer Symposium meeting in December showed how SBT-6050 drove multiple antitumor immune mechanisms in vitro and a mouse surrogate showed efficacy as a single agent and in combination with trastuzumab in vivo.
“We especially selected TLR8 as a payload target to harness the power of myeloid cells,” Valerie Odegard, Silverback’s chief scientific officer, told BioWorld. “The challenge really has been the ability to safely administer TLR8 agonists.”
Odegard, the former vice president of research at Juno Therapeutics Inc., where she oversaw discovery and translational research for the company's cancer immunotherapies, noted that HER2-expressing tumors have traditionally been responsive to immunotherapy.
When it enters the clinic, Seattle-based Silverback plans to focus on the HER2-expressing tumors that are typical in a phase I patient population: those who have progressed through standard-of-care therapies.
“The patient population is again broader than we would have thought about 15 years ago,” Peter Thompson, Silverback’s president and CEO, told BioWorld. “It encompasses not just breast cancer but lung cancer, colon cancer and gastric cancer, a breadth of patient populations.”
Thompson referred to Silverback as “the tip of the spear” in understanding the science associated with that drug composition class.
“It’s been fascinating for us to discover the ability to create a composition class that is conditionally active,” he said, “activating myeloid cells, engaging the innate immune system.”
The preclinical data show, the company noted, the SBT-6050 mouse surrogate is curative as a single agent in a human xenograft model lacking T, B and NK cells, which demonstrated myeloid cells’ potential to mediate antitumor activity.
SBT-6050 and trastuzumab bind to epitopes on HER2, which enable potential trastuzumab-based combinations in patients. The combination of a low dose of SBT-6050 mouse surrogate with trastuzumab in a HER2-positive xenograft model enhanced the antitumor activity observed with either agent alone, the company reported.
In November 2019, Silverback’s preclinical data were presented at the 34th Society for Immunotherapy of Cancer meeting and showed that, in the presence of HER2-expressing MDA-MB-468 tumor cell lines, SBT-6050 activated human myeloid cells to produce pro-inflammatory and TH1 priming cytokines such as IL-12p40, IFN-gamma, TNF-alpha, IL-18 and granzyme B, according to Cortellis.
Silverback’s technology, Immunotac, is driving the company’s pipeline. The platform is designed to create the molecules that are systemically administered but act only at the disease site, sparing otherwise healthy tissue from off-target side effects. The molecules are for modulating biologic pathways in not only oncology but also in virology and fibrotic diseases.
The company has filed more than 15 patent families covering the Immunotac platform and related candidates, according to Cortellis.
U.S. Venture Partners led the funding round, with participation from new investors, including Nextech Invest Ltd., Hunt Investment Group, Pontifax Venture Capital, Colt Ventures LP and NS Investment. Existing investors who participated include Orbimed Advisors LLC, Bristol-Meyers Squibb Co. and Alexandria Venture Investments LLC.
This fundraiser is a follow-up to Silverback’s extended series A of $47.5 million in September 2018, which was led by Orbimed with help from Alexandria Venture and by then-new investor Celgene Corp. Since it began raising money, the company has brought in more than $125 million.