Silverback Therapeutics Presents Interim Clinical Results from the Ongoing Phase 1/1b Study of SBT6050 Alone or In Combination with Pembrolizumab in Patients with Advanced or Metastatic HER2-Expressing Solid Tumors

– Proof-of-mechanism established with activation of myeloid and T/NK cells, and evidence of SBT6050 payload localization in the tumor microenvironment –

– SBT6050 demonstrated a manageable safety profile with adverse events consistent with on-mechanism immune activation, both as a monotherapy or in combination with pembrolizumab –

– Early signals of anti-tumor activity observed in a heavily pre-treated, heterogeneous population –

– Management to host conference call today at 6:30 AM ET –

Silverback Therapeutics, Inc. (Nasdaq: SBTX) (“Silverback”), a clinical-stage biopharmaceutical company leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered, tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases, today presented interim clinical results from a Phase 1/1b clinical study of SBT6050 as a monotherapy and in combination with pembrolizumab in patients with advanced or metastatic HER2-expressing or amplified solid tumors, at the 2021 European Society for Medical Oncology Congress.

“Over this past year, we have gathered compelling data with clear signals of SBT6050’s pharmacological activity, marked by the activation of both the innate and adaptive immune response in patients,” said Laura Shawver, Ph.D., chief executive officer of Silverback. “We look forward to moving into expansion cohorts and to expanding our clinical development plan to include combination with standard-of-care trastuzumab-containing regimens.”

As of August 1, 2021, 40 patients with advanced or metastatic HER2-expressing or amplified solid tumors were enrolled into the SBT6050-101 trial. SBT6050 dose levels ranged from 0.3 to 1.2 mg/kg in the monotherapy dose escalation arm (Part 1), and 0.15 and 0.3 mg/kg in the pembrolizumab combination arm (Part 3). Patients received between 1 and 17 doses of SBT6050.

As a monotherapy and in combination with pembrolizumab, SBT6050 was generally well-tolerated, with an adverse event profile that is consistent with immune system activation and considered on-mechanism. “The adverse event profile thus far has been very manageable and importantly, suggests the potential to combine with other standard of care agents,” said Samuel Klempner, MD, Medical Oncologist at the Massachusetts General Hospital. “The signals of anti-tumor activity are encouraging and its complementary mechanism of action with standard-of-care agents makes SBT6050 attractive for combination regimens.”

Initial Safety Data

• The most frequent treatment-related adverse events were consistent with immune activation, and included injection site reactions, fever and chills, hypotension, nausea, vomiting, and fatigue. These were mostly Grade 1 or 2 in nature, and no Grade 4 or higher related adverse events were reported.
• At higher dose levels, dose limiting toxicities (DLTs) were observed and included Grade 3 hypotension, injection site reaction, fever, and hypoxia. These DLTs resolved with supportive care.
• Cytokine release syndrome (CRS) > Grade 2 was not observed at any dose level.

Pharmacokinetic and Pharmacodynamic Data

• SBT6050 exposures increased with dose and exhibited a linear PK profile at 0.6 mg/kg and higher. Linear exposure is evidence of saturation of receptor mediated clearance.
• Conjugate stability was assessed using a highly sensitive assay, and no active levels of SBT6050’s free payload were detected in the blood and any amount of free payload was absent in 98% of all blood samples tested.
• SBT6050 induces pharmacologic activity indicative of myeloid and NK/T cell activation at all dose levels, with effects plateauing at 0.6 mg/kg.
• Pharmacodynamic activity is maintained with repeat dosing of SBT6050.

Anti-Tumor Activity

• Early signals of anti-tumor activity were observed in a heavily pre-treated, heterogeneous population.
• Among 18 evaluable patients for tumor types of interest, one patient with HER2 IHC 2+ NSCLC had a confirmed partial response (-55% per RECIST 1.1 criteria), maintained at the most recently available scan obtained at 36 weeks post-enrollment, and 8 weeks after discontinuing study treatment. In addition, stable disease was reported in seven patients.

SBT6050 targets the pertuzumab binding domain of HER2 and is designed to be used in combination with standard of care agents, including trastuzumab-containing regimens. Silverback will be discussing details of its expanded clinical development strategy on the scheduled investor webcast today.

Conference Call and Webcast on Thursday, September 16, 2021, at 6:30 AM ET

Silverback’s management team will host a conference call today at 6:30 AM ET. A live webcast, including slides, can be accessed through the Events section of the Company’s website at https://ir.silverbacktx.com/news-events/events. An archived replay will be available shortly after the conclusion of the event.

About SBT6050

SBT6050 is the first of a new class of targeted immuno-oncology agents designed to direct a TLR8 agonist linker-payload to activate myeloid cells in tumors expressing moderate to high levels of HER2. TLR8 is expressed in myeloid cell types prevalent in human tumors and TLR8 agonism can activate a broad spectrum of anti-tumor immune mechanisms, including pathways involved in the innate and adaptive immune response. SBT6050 was specifically designed to bind to the HER2 sub-domain II, the pertuzumab epitope, to enable combinations with trastuzumab-containing therapies. SBT6050 is currently being evaluated in a Phase 1/1b trial in patients with advanced or metastatic HER2-expressing or amplified solid tumors.

About Silverback Therapeutics

Silverback Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on leveraging its proprietary ImmunoTAC technology platform to develop systemically delivered and tissue targeted therapeutics for the treatment of cancer, chronic viral infections, and other serious diseases. Silverback’s platform enables the strategic pairing of proprietary payloads that modulate key disease modifying pathways with monoclonal antibodies directed at specific disease sites. Initially, Silverback is creating a new class of targeted immuno-oncology agents that direct a TLR8 agonist myeloid cell activator to the tumor microenvironment in solid tumors to promote cancer cell killing. Silverback Therapeutics is located in Seattle, Washington. To learn more, visit www.silverbacktx.com.

Forward-Looking Statements

This news release contains certain forward-looking statements that involve risks and uncertainties that could cause actual results to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. Such forward-looking statements include statements regarding, among other things, Silverback’s plans and ability to bring new treatments to patients in need, including potential combination efforts, and the progress and expected timing of Silverback’s drug development programs and clinical trials. Factors that may cause actual results to differ materially include the risk that compounds that appeared promising in early research or clinical trials do not demonstrate safety and/or efficacy in later preclinical studies or clinical trials, the risk that Silverback may not obtain approval to market its product candidates, uncertainties associated with performing clinical trials, regulatory filings and applications, risks associated with reliance on third parties to successfully conduct clinical trials, the risks associated with reliance on outside financing to meet capital requirements, and other risks associated with the process of discovering, developing and commercializing drugs that are safe and effective for use as human therapeutics, and in the endeavor of building a business around such drugs. You are urged to consider statements that include the words "may," "will," "would," "could," "should," "believes," "estimates," "projects," "promise," "potential," "expects," "plans," "anticipates," "intends," "continues," "designed," "goal," or the negative of those words or other comparable words to be uncertain and forward-looking. For a further list and description of the risks and uncertainties that Silverback faces, please refer to Silverback’s periodic and other filings with the Securities and Exchange Commission, which are available at www.sec.gov. Such forward-looking statements are current only as of the date they are made, and Silverback assumes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise.

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