On December 12, 2019 Silverback Therapeutics, Inc., a biopharmaceutical company developing a pipeline of systemically delivered, locally active therapies, reported the presentation of preclinical data supporting development of its lead ImmunoTAC candidate, SBT6050, at the San Antonio Breast Cancer Symposium (SABCS) (Press release, Silverback Therapeutics, DEC 12, 2019, View Source [SID1234552325]). The data were presented today in Spotlight Oral and Poster Presentations at the Henry B. Gonzalez Convention Center in San Antonio, Texas (Program #PD4-09, Abstract #924).

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"Our preclinical data continue to highlight the potential for single agent clinical activity with SBT6050, even in settings with diminished or absent T cell infiltrates, and now demonstrate the opportunity for enhanced activity in combination with trastuzumab. We are excited to rapidly advance SBT6050 into the clinic."

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The presentation, titled "Preclinical studies support the development of SBT6050, an anti-HER2 antibody conjugated to a potent TLR8 agonist, for treatment of moderate and high HER2 expressing tumors," shows that SBT6050 effectively activates human myeloid cells and drives multiple anti-tumor immune mechanisms in a HER2 dependent manner in vitro, and an SBT6050 mouse surrogate exhibits potent anti-tumor efficacy as a single agent and in combination with trastuzumab in vivo. Unlike other innate immune agonists that have been limited to topical or intratumoral administration, SBT6050 is designed for systemic delivery and tumor-localized activity.

In preclinical studies, robust, durable single agent activity is observed with the SBT6050 mouse surrogate in multiple syngeneic mouse tumor models, including those with low tumor infiltrating lymphocytes, a feature commonly observed in HER2-expressing malignancies. Importantly, the SBT6050 mouse surrogate is curative as a single agent in a human xenograft model lacking T, B, and NK cells, demonstrating the potential of myeloid cells to mediate strong anti-tumor activity. SBT6050 and trastuzumab bind to distinct epitopes on HER2, enabling potential trastuzumab-based combinations in patients. A combination of low dose SBT6050 mouse surrogate with trastuzumab in a HER2-positive human xenograft model greatly enhanced the anti-tumor activity observed with either agent alone. Collectively, these data demonstrate the potential for clinical activity with SBT6050 in HER2-expressing malignancies and highlight development opportunities in clinical combination with trastuzumab.

"SBT6050’s ability to drive a broad spectrum of anti-tumor immune responses through localized and potent activation of human myeloid cells has not been achieved by other cancer immunotherapies," said Valerie Odegard, Ph.D., Silverback’s chief scientific officer. "Our preclinical data continue to highlight the potential for single agent clinical activity with SBT6050, even in settings with diminished or absent T cell infiltrates, and now demonstrate the opportunity for enhanced activity in combination with trastuzumab. We are excited to rapidly advance SBT6050 into the clinic."

Added Naomi Hunder, M.D., Silverback’s senior vice president of clinical development, "Despite advances in treatment options for patients with HER2-expressing tumors, significant unmet medical need remains, and immune checkpoint inhibitors have demonstrated activity in only a subset of these patients. Preclinical data indicate SBT6050 may be useful as a single agent therapeutic or in combination with trastuzumab-based therapies, providing a much needed immunotherapeutic option for patients with HER2-expressing disease. We plan to initiate clinical investigation of SBT6050 in 2020."

About Silverback’s Platform Technology

Silverback’s proprietary technology and integrated R&D approach enables the design and development of ImmunoTAC therapeutics that can be administered systemically but act only at the sites of disease. This approach is designed to spare healthy tissues from unwanted side effects, while modifying disease processes in a targeted and potent manner. Silverback’s platform is useful for developing 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. Silverback has over 20 patent families directed to the platform and related product candidates.