pertuzumab zuvotolimod (SBT6050) / ARS Pharma - LARVOL DELTA

Discovery of DN027262, a Highly Potent and Selective Active TLR8-ISAC for the Treatment of Solid tumor (EACR 2024) - "Data showed our TLR8-ISAC has better antitumor efficacy than SBT6050...Consistently, in vivo cynomolgus monkey studies by consecutive treatments with DN027262 at different doses resulted in a significant increase of immune system cells including monocytes, cDCs and natural killer (NK) cells, correlated with TLR8 activation. All these changes were back to normal after a period of recovery (2-3 weeks).Conclusion DN027262 exhibited a remarkable anti-tumor activity both in vitro and in vivo and provided a favorable safety window, supporting novel insights for immunotherapies."

Oncology • Solid Tumor • TLR7 • TLR8

[VIRTUAL] A phase 1/1b study of SBT6050, a HER2-directed monoclonal antibody conjugated to a toll-like receptor 8 agonist, in subjects with advanced HER2-expressing solid tumors (SITC 2020) - P1 | "SBT6050 is designed to activate human myeloid cells only in the presence of moderate-to-high HER2 expression (immunohistochemistry [IHC] 2+ or 3+) and binds to the same epitope as pertuzumab...Preclinical studies also support combinations with checkpoint inhibitors and with trastuzumab to further enhance antitumor activity...Pharmacokinetics, immunogenicity, and antitumor activity will be evaluated and pharmacodynamic markers of myeloid cell activation will be assessed in peripheral blood and on-treatment tumor biopsies. Results N/A Conclusions N/A"

Clinical • IO Biomarker • P1 data • Oncology • Solid Tumor • HER-2

"Silverback was using a SC approach for their ISACs (TLR conjugates, e.g. SBT6050), but the development has been terminated. https://t.co/0RAMthVPgo" (@Raffaele_1985)

A phase 1/2 study of SBT6050 combined with trastuzumab deruxtecan (T-DXd) or trastuzumab and tucatinib with or without capecitabine in patients with HER2-expressing or HER2-amplified cancers (SITC 2021) - P1 | "Background SBT6050 is a novel therapeutic comprising a selective small molecule toll-like receptor 8 (TLR8) agonist linked to the HER2-directed monoclonal antibody pertuzumab, allowing for combination with trastuzumab-based agents and regimens. Pharmacodynamic markers of myeloid and NK/T cell activation will be assessed in peripheral blood and on-treatment tumor biopsies. Circulating tumor DNA will be evaluated as an exploratory assessment."

Clinical • IO biomarker • P1/2 data • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HER-2 • SIRPA • TLR8

A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers (clinicaltrials.gov) - P1/2 | N=2 | Terminated | Sponsor: Silverback Therapeutics | Trial completion date: Apr 2023 ➔ Jul 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Apr 2023 ➔ Jul 2022; Sponsor decision based on strategic re-alignment

Combination therapy • Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced HER2 Expressing Solid Tumors (clinicaltrials.gov) - P1 | N=58 | Active, not recruiting | Sponsor: Silverback Therapeutics | Recruiting ➔ Active, not recruiting | N=344 ➔ 58 | Trial completion date: Aug 2024 ➔ Dec 2022 | Trial primary completion date: Aug 2023 ➔ Dec 2022

Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • HER-2

A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers (clinicaltrials.gov) - P1/2 | N=1 | Active, not recruiting | Sponsor: Silverback Therapeutics | Recruiting ➔ Active, not recruiting | N=328 ➔ 1 | Trial completion date: Dec 2025 ➔ Apr 2023 | Trial primary completion date: Dec 2023 ➔ Apr 2023

Combination therapy • Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Antibody-Drug Conjugates Targeting the Human Epidermal Growth Factor Receptor Family in Cancers. (PubMed, Front Mol Biosci) - "A third HER2-directed ADC, disitamab vedotin (RC48), has been approved for locally advanced or metastatic gastric or gastroesophageal junction cancer by the NMPA (National Medical Products Administration) of China in 2021. In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges."

Journal • Review • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • ERBB4 • HER-2

Silverback Therapeutics Updates Strategic Priorities and Reports Fourth Quarter and Full Year 2021 Financial Results (Businesswire) - "Silverback has discontinued the SBT6050 development program....Further development was discontinued based on limited monotherapy anti-tumor activity and cytokine-related adverse events that limited the dose in combination with pembrolizumab."

Discontinued • Oncology • Solid Tumor

A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers (clinicaltrials.gov) - P1/2; N=328; Recruiting; Sponsor: Silverback Therapeutics; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Silverback Therapeutics Presents SBT6050-201 Trial in Progress Poster at Society for Immunotherapy of Cancer's (SITC) 36th Annual Meeting (Businesswire) - "Silverback Therapeutics, Inc....presented a trial-in-progress poster on SBT6050-201 at the Society for Immunotherapy of Cancer's (SITC) 36th Annual Meeting, held virtually from November 10-14, 2021. SBT6050-201 is a Phase 1/2 study evaluating SBT6050 in combination with trastuzumab deruxtecan (Enhertu), or with trastuzumab (Herceptin) and tucatinib (Tukysa) with or without capecitabine, in patients with HER2-expressing or HER2-amplified gastroesophageal, non-small cell lung, breast, and colorectal cancers...We look forward to initiating clinical evaluation of these combinations in the first quarter of 2022.'"

Clinical protocol • Trial status • Colorectal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Silverback Therapeutics Reports Third Quarter 2021 Financial Results and Provides Business Update (Businesswire) - "Selected go forward dose of 0.3 mg/kg SBT6050 in combination with anti-PD-1 therapy in expansion cohorts. Silverback is prioritizing combination with Libtayo in gastroesophageal and non-small cell lung cancers and plans to initiate these expansion cohorts in the fourth quarter of 2021....SBT6290 (Nectin4-TL8 ImmunoTAC): Silverback remains on track to initiate the phase 1/1b trial in the first quarter of 2022, and plans to enroll patients with bladder, non-small cell lung, triple negative breast, and head and neck cancers in dose escalation."

New P1 trial • New trial • Bladder Cancer • Breast Cancer • GastroEsophageal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Triple Negative Breast Cancer

A Safety and Activity Study of SBT6050 in Combination With Other HER2-directed Therapies for HER2-positive Cancers (clinicaltrials.gov) - P1/2; N=328; Not yet recruiting; Sponsor: Silverback Therapeutics

Clinical • Combination therapy • New P1/2 trial • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

[VIRTUAL] Interim results of a phase I/Ib study of SBT6050 monotherapy and pembrolizumab combination in patients with advanced HER2-expressing or amplified solid tumors (ESMO 2021) - P1 | "Based on preliminary safety data, SBT6050 given alone or in combination with pembrolizumab has a manageable safety profile. Related TEAEs are consistent with immune activation. A single-agent dose of 0.6 mg/kg administered Q2 weeks had a tolerable safety profile, drug exposure that reflects evidence of target saturation, and pharmacodynamics indicative of myeloid, NK and T cell activation."

Clinical • Monotherapy • P1 data • Oncology • Solid Tumor • HER-2 • IFNG • TLR8

[VIRTUAL] Immunomodulatory Antibody Conjugates for the Treatment of Cancer & Chronic Viral Infections (ADC-USA 2021) - "Synopsis An overview of Silverback’s ImmunoTAC (Immunomodulatory Targeted Antibody Conjugate) technology platform Discussing the discovery and development of ImmunoTAC molecules containing a TLR8 agonist payload designed to stimulate local activation of myeloid cells Examining how broad and versatile potential of the ImmunoTAC platform is exemplified by oncology (SBT6050 and SBT6290) and virology (SBT8230) development candidates"

Immune Modulation • Infectious Disease • Inflammation • Oncology • TLR8

[VIRTUAL] A phase 1/1b study of SBT6050, a HER2-directed monoclonal antibody conjugated to a toll-like receptor 8 agonist, in subjects with advanced HER2-expressing solid tumors (SITC 2020) - P1 | "SBT6050 is designed to activate human myeloid cells only in the presence of moderate-to-high HER2 expression (immunohistochemistry [IHC] 2+ or 3+) and binds to the same epitope as pertuzumab...Preclinical studies also support combinations with checkpoint inhibitors and with trastuzumab to further enhance antitumor activity...Pharmacokinetics, immunogenicity, and antitumor activity will be evaluated and pharmacodynamic markers of myeloid cell activation will be assessed in peripheral blood and on-treatment tumor biopsies. Results N/A Conclusions N/A"

Clinical • IO biomarker • P1 data • Oncology • Solid Tumor • HER-2

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 (Businesswire) - P1/1b, N=294; NCT04460456; Sponsor: Silverback Therapeutics; "Silverback Therapeutics...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...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....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."

P1 data • PK/PD data • Oncology • Solid Tumor

Silverback Therapeutics to Present Data from its Phase 1/1b Clinical Trial of SBT6050 at the European Society for Medical Oncology (ESMO) 2021 Virtual Congress (Businesswire) - "Silverback Therapeutics, Inc...announced that interim data from the dose-escalation portion of its Phase 1/1b clinical trial evaluating SBT6050 as a monotherapy and in combination with pembrolizumab in patients with advanced or metastatic HER2-expressing or amplified solid tumors will be presented at the upcoming European Society for Medical Oncology (ESMO) 2021 Congress from September 16-21, 2021."

P1 data • Oncology • Solid Tumor

Silverback Therapeutics Reports Second Quarter 2021 Financial Results and Provides Business Update (Businesswire) - “We are deeply appreciative of the patients, their families, and our clinical investigators who continue to contribute to the SBT6050-101 clinical trial, and we look forward to providing the first update of the clinical data at the ESMO conference in September.”

P1 data • Oncology • Solid Tumor

Silverback Therapeutics Announces Clinical Supply Agreement with Regeneron to Evaluate SBT6050 in Combination with Libtayo (cemiplimab), initially in HER2-expressing Non-Small Cell Lung and Gastric Cancers (Businesswire) - "Silverback Therapeutics...announced a clinical supply agreement with Regeneron for Libtayo® (cemiplimab). The supply agreement supports the evaluation of Libtayo®, a PD-1 inhibitor, in combination with SBT6050, 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."

Licensing / partnership • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Silverback Therapeutics Reports First Quarter 2021 Financial Results (Businesswire) - "SBT6050 (HER2-TLR8 ImmunoTAC) continues to advance through monotherapy and pembrolizumab combination dose escalation arms of the Phase 1/1b clinical study. Silverback is on track to deliver interim clinical data from the monotherapy dose escalation arm of the study in the second half of 2021....GLP toxicology studies have commenced for SBT6290 (Nectin4-TLR8 ImmunoTAC), with an IND submission anticipated in the fourth quarter of 2021."

IND • P1 data • Oncology • Solid Tumor

Silverback Therapeutics Reports Fourth Quarter and Full Year 2020 Financial Results and Recent Corporate Updates (Businesswire) - “SBT6050…Enrollment is ongoing in Part 1 of the study (SBT6050 monotherapy dose escalation) and treatment has been initiated in Part 3 of the study (SBT6050 plus pembrolizumab dose-escalation). Silverback is on track to deliver interim clinical data from Part 1 of the study in the second half of 2021; SBT6290…IND application is expected in the fourth quarter of 2021. The initiation of a Phase 1/1b clinical study is anticipated in the first quarter of 2022.”

IND • New P1 trial • P1 data • Oncology • Solid Tumor

A Study of SBT6050 Alone and in Combination With Pembrolizumab in Patients With Advanced HER2 Expressing Solid Tumors (clinicaltrials.gov) - P1; N=294; Recruiting; Sponsor: Silverback Therapeutics; N=210 ➔ 294

Clinical • Combination therapy • Enrollment change • Oncology • Solid Tumor

Silverback Therapeutics to Present Data on Two Programs at The Society for Immunotherapy of Cancer’s (SITC) 35th Anniversary Annual Meeting (Businesswire) - “Silverback will present a trial-in-progress update on SBT6050-101, a Phase 1/1b dose-escalation and expansion clinical trial in patients with advanced or metastatic HER2-expressing solid tumors...In addition, the Company will present preclinical data on SBT6290, its second product candidate comprised of the same TLR8 linker-payload used in SBT6050 conjugated to a Nectin4-specific monoclonal antibody…‘We are encouraged by SBT6290’s preclinical profile to date and anticipate submitting an IND for this program in the fourth quarter of 2021'."

IND • Preclinical • Trial status • Oncology • Solid Tumor

Silverback Therapeutics Initiates Phase 1 Clinical Study of SBT6050 (Businesswire) - "Silverback Therapeutics…announced initiation of a Phase 1 clinical study of SBT6050, a novel therapeutic comprising a specific small molecule toll-like receptor 8 (TLR8) agonist conjugated to a HER2-directed monoclonal antibody…Dosing has initiated in the Phase 1 clinical study, an open-label, multicenter, dose escalation and expansion cohort study that will evaluate the safety and tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of SBT6050 in adults with HER2-expressing solid tumors."

Enrollment open • Oncology • Solid Tumor