Seattle-based Silverback Therapeutics™, a biopharmaceutical company pioneering a new class of immune-modulating ImmunoTAC™ drug conjugates targeting previously inaccessible disease pathways, confirmed that it has raised U.S. $78.5 million Series B financing an oversubscribed funding round.

U.S. Venture Partners led the round, with participation from new investors including Nextech Invest, Hunt Investment Group, Pontifax Venture Capital, Colt Ventures and NS Investment. Existing investors participating in the financing include OrbiMed Advisors, Bristol-Meyers Squibb and Alexandria Venture Investments.

Silverback is expected to use the proceeds of the funding round to support the ongoing development of SBT6050, an anti-HER2 antibody-drug conjugated.

Silverbacks’ investigational agent, SBT6050, is comprised of a potent TLR8 agonist conjugated to a HER2-directed monoclonal antibody, designed to activate myeloid cells only in the presence of HER2-expressing solid tumors with moderate-to-high expression levels.

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In mouse HER2-expressing tumor models, a surrogate molecule of SBT6050 activated both innate and adaptive immune responses, resulting in single-agent efficacy. Due to the localized activation of myeloid cells, TLR conjugates do not cause an overproduction of peripheral cytokines in preclinical models.

The funds will also be used to advance Silverback’s pipeline of ImmunoTAC™ programs. The Company expects to file an Investigational New Drug Application (“IND”) and initiate a clinical trial for SBT6050 this year.

Checkpoint inhibition
“Tumors resistant to checkpoint inhibition lack T-cells but are replete with myeloid cells. TLR8 activation of tumor-resident myeloid cells results in potent anti-tumor immune responses, but effective delivery has been the key challenge,” noted Valerie Odegard, Ph.D., Silverback’s chief scientific officer.

“Preclinical studies [have] demonstrate that systemic delivery of a TLR agonist with tumor-localized activity dramatically rewires the tumor microenvironment, resulting in durable, single-agent efficacy in tumors refractory to checkpoint blockade,” Odegard added.

Potent therapies
Silverback’s ImmunoTAC™ approach is designed to spare healthy tissues from unwanted adverse effects while, at the same time, modifying disease processes in a targeted and potent manner. The company’s platform is useful for developing multiple systemic therapies that can modulate fundamental pathways underlying serious or life-threatening diseases in a targeted manner, in contrast to traditional antibody and small molecule-based approaches that have not been successful due to inadequate activity and/or unacceptable toxicities.

Data presented during the 2019 annual meeting of the American Association of Cancer Research (AACR) for the first time demonstrate that the company’s technology was able to localize delivery of potent therapies to specific sites in the body.

“[The] data showed the successful, specific delivery of a TLR agonist to HER2-expressing tumor cells upon systemic administration—thereby addressing a fundamental challenge previously limiting the use of innate immune agonists to topical and intratumoral administration, largely due to toxicity arising from widespread myeloid cell activation with systemic use of these agents. With this validating data in hand, we are applying our technology to a broad range of targets and diseases,” explained Peter Thompson, M.D., Silverback’s co-founder, chief executive officer, and chairman.

“We are pleased to attract a group of world-class investors who believe in our bold vision to develop potent immune-modulating agents that can be delivered systemically but act locally at the site of disease. With these additional resources, we’re focused on advancing our lead program into the clinic this year and progressing our preclinical pipeline assets towards the clinic,” Thompson said.

Jonathan Root, M.D., general partner at USVP.

Board of directors
In addition to the successful financing round, Jonathan Root, M.D., general partner at USVP, and Thilo Schroeder, Ph.D., partner at Nextech Invest Ltd., have joined Silverback’s board of directors.

Root spent nine years in clinical practice before joining USVP in 1995 and becoming a general partner in 1997. Before USVP, he was on the faculty and clinical staff at The New York Hospital-Cornell Medical Center in New York City.

Root is currently on the boards of several USVP portfolio companies and is also a former board member for the National Venture Capital Association.

Thilo Schroeder joined Nextech as a partner in 2012, helping grow and shape the organization as a leading oncology-focused venture firm.

Thilo Schroeder, Ph.D. has a passion for precision medicines in cancer with a focus on identifying first and best-in-class targeted therapies regardless of drug modality. Since 2012, Schroeder has helped grow and shape Nextech as a leading oncology-focused venture firm.

He began his biotech career at the pioneering cancer immunology company Micromet (which was acquired by Amgen) while studying at Ecole Supérieure de Biotechnologie de Strasbourg.

Schroeder is currently a member of boards of several private biotechnology companies, including Revolution Medicines, IDEAYA Biosciences, PMV Pharma and ImaginAb and is a board observer of BlackDiamond Therapeutics. Past board seats include Blueprint Medicines and Peloton Therapeutics (acquired by Merck).

He obtained his Ph.D., focused on protein engineering in the development of Designed Ankyrin Repeat Proteins (DARPins).

“The Silverback team is building a platform technology capable of unlocking potent immuno-modulatory pathways using an established antibody-guided approach for targeting disease sites,” said Root, said.

“I look forward to supporting the company’s evolution as it moves these compelling therapies into the clinic, starting with SBT6050,” he concluded.

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