PD-L1 ISAC / Bolt Biotherapeutics - LARVOL DELTA

Discovery of a PD-L1-directed ISAC optimized for the activation of PD-L1-expressing myeloid cells to drive potent antitumor immune responses (SITC 2025) - "Consistent with their activity in vitro, Fc-competent PD-L1 ISACs demonstrated greater antitumor efficacy than Fc-attenuated variants in vivo.Conclusions PD-L1 ISACs drive powerful innate and adaptive immune responses through the targeted activation of PD-L1-expressing myeloid cells in tumors and TDLNs. A PD-L1 ISAC with an intact Fc and dual TLR7/8 agonist payload has the potential for enhanced immune activation and antitumor efficacy."

IO biomarker • Oncology • PD-L1

Discovery of a PD-L1-directed ISAC optimized for the activation of PD-L1-expressing myeloid cells to drive potent antitumor immune responses (SITC 2025) - "Consistent with their activity in vitro, Fc-competent PD-L1 ISACs demonstrated greater antitumor efficacy than Fc-attenuated variants in vivo.Conclusions PD-L1 ISACs drive powerful innate and adaptive immune responses through the targeted activation of PD-L1-expressing myeloid cells in tumors and TDLNs. A PD-L1 ISAC with an intact Fc and dual TLR7/8 agonist payload has the potential for enhanced immune activation and antitumor efficacy."

IO biomarker • Oncology • PD-L1

PD-L1-directed ISACs target host immune cells to drive powerful antitumor immune responses in a manner distinct from conventional PD-1/PD-L1 blockade (AACR 2025) - "PD-L1 ISACs induced robust, target-dependent activation of human myeloid cells cocultured with PD-L1-expressing tumor cells, as measured by secretion of cytokines such as IL-12 and TNFα. PD-L1 ISACs also strongly activated macrophages and DCs polarized to express high levels of PD-L1, demonstrating the ability to directly activate PD-L1-expressing APCs. Systemically administered PD-L1 ISACs were well tolerated in mice and showed improved efficacy over anti-PD-L1 antibodies, with tumor regression including complete responses observed in syngeneic and xenograft models."

Immune cell • IO biomarker • Hematological Malignancies • Oncology • IL12A • TNFA

Bolt Biotherapeutics Presents Preclinical Results for Next-Generation Boltbody ISACs targeting…PD-L1 at AACR Annual Meeting 2025 (GlobeNewswire) - "Key results are below: PD-L1 ISACs directly activate and reprogram PD-L1-expressing myeloid cells in the TME to promote innate and adaptive antitumor immunity; PD-L1 ISACs elicit complete regressions and immunological memory in models that are resistant to PD-1/PD-L1 checkpoint inhibitor therapy; Mechanistic studies indicate that PD-L1 expression by either tumor or immune cells is sufficient to drive antitumor efficacy...; Favorable safety profile was demonstrated in non-GLP NHP toxicology studies supporting use in combination with SoC therapies & other agents."

Preclinical • Solid Tumor

Bolt Biotherapeutics to Present Data from Phase 1 Dose-Escalation Clinical Study of BDC-3042 at AACR Annual Meeting 2025 (GlobeNewswire) - "Bolt Biotherapeutics...announced it will present data from the Phase 1 dose-escalation clinical study of BDC-3042 in patients with advanced cancers at the American Association for Cancer Research (AACR) Annual Meeting....BDC-3042 is a proprietary agonist antibody that targets dectin-2, an immune-activating receptor expressed by tumor-associated macrophages (TAMs). This single-agent, dose-escalation Phase 1 clinical study is evaluating BDC-3042 in patients with metastatic or unresectable solid tumors including non-small cell lung cancer (NSCLC). Bolt will also be presenting preclinical data from two of its pipeline programs, Boltbody ISACs targeting CEA and PD-L1."

P1 data • Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

PD-L1-targeted ISAC combines myeloid cell activation, immune-checkpoint inhibition and ADCP to improve anti-tumor efficacy over anti-PD-L1 antibodies in preclinical models (AACR 2022) - "These preclinical data demonstrate the potential of a PD-L1-targeted ISAC as a novel multifunctional therapeutic that may improve efficacy of PD-L1/PD-1 inhibition by combining three mechanisms of action into a single molecule: TLR-mediated myeloid cell activation, T cell activation through immune-checkpoint inhibition as well as ADCP."

Checkpoint inhibition • IO biomarker • Preclinical • Oncology • IFNG • TLR7 • TNFA

Bolt Biotherapeutics Reports Four Quarter and Full Year 2021 Financial Results and Provides Business Highlights (GlobeNewswire) - "BDC-1001 for the treatment of patients with HER2-expressing solid tumors on track for recommended Phase 2 dose identification later in 2022; BDC-1001 combination study arm with OPDIVO® (nivolumab) progressing well; Preclinical data on multiple pipeline programs will be presented at AACR 2022, including BDC-2034, BDC-3042, and a PD-L1 ISAC."

Preclinical • Trial status • Oncology • Solid Tumor