On November 12, 2021 Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biotechnology company pioneering a new class of immuno-oncology agents that combine the targeting precision of antibodies with the power of both the innate and adaptive immune systems, reported the company will be presenting posters with new data from three of its pipeline programs on Saturday, Nov. 13, at the 2021 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, being held virtually and in person in Washington, D.C. from Nov. 10-14 (Press release, Bolt Biotherapeutics, NOV 12, 2021, View Source [SID1234618693]). Each presentation highlights the progress made in preclinical studies to demonstrate the potential for each pipeline candidate as a novel approach for the treatment for cancer.

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"We are presenting new data for three of our pipeline programs that demonstrate the depth of our technology platform and the expertise of our team in modulating myeloid cell biology to develop promising therapeutic candidates," said David Dornan, Ph.D., Bolt Biotherapeutics’ Chief Scientific Officer. "Repolarizing tumor-associated macrophages, or TAMs, to become tumor destructive via the novel target Dectin-2 is groundbreaking work that may be synergistic with our entire Boltbody ISAC portfolio. Our work targeting CEA and PD-L1 reinforces our commitment to develop therapeutics that could have promising activity against solid tumors where limited treatment options are available."

Highlights of the three poster presentations follow, and copies of the posters are available on the Bolt Biotherapeutics website.
Poster #784: "BDC-2034: Discovery of a CEA-targeting Immune-Stimulating Antibody Conjugate (ISAC) for Solid Tumors"
Presenter: William G. Mallet, Ph.D.
Details: Saturday, Nov. 13, 2021, 7:00 a.m. – 8:30 p.m. EST, Poster Hall

Key findings from the study:
CEA is a well-validated tumor antigen for the development of targeted therapies addressing multiple types of solid tumors, such as colon cancer, where new treatment options are urgently needed. Given the abundance of innate immune cells in CEA-expressing cancers, innate immune stimulation presents a promising therapeutic strategy. Applying Boltbody platform technology, Bolt Biotherapeutics scientists have developed a novel CEA-targeted ISAC, BDC-2034, to exploit over-expression of CEA in cancers. BDC-2034 is designed to trigger the innate immune system, leading to adaptive anti-tumor immunity and tumor destruction.

BDC-2034 comprises a novel CEA-targeted, pro-phagocytic antibody conjugated to a proprietary TLR7/8 agonist payload. Both elements of this molecule are finetuned for selective immune activation in tumors.
New data reported at SITC (Free SITC Whitepaper) 2021 demonstrate both tumor cell clearance and innate immune activation in cellular and in vivo models of CEA-expressing cancers. Further, systemic administration in tumor-bearing animals results in tumor-selective immunity.
Based on these data, Bolt Biotherapeutics designated BDC-2034 as a clinical candidate and is currently conducting IND-enabling studies with the expectation to initiate BDC-2034 clinical development in 2022.
Poster #782: "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"
Presenter: Marcin Kowanetz, Ph.D.
Details: Saturday, Nov. 13, 2021, 7:00 a.m. – 8:30 p.m. EST, Poster Hall

Key findings from the study:
Bolt Biotherapeutics scientists are presenting for the first time preclinical data on a novel multifunctional PD-L1-targeted Boltbody ISAC that has demonstrated the potential to improve upon the efficacy of PD-L1/PD-1 inhibition, especially in tumor types that do not respond well to immune-checkpoint inhibition.

Bolt Biotherapeutics’ PD-L1 ISAC uniquely combines three mechanisms of action: the ADCP and myeloid cell activation of an ISAC, plus immune-checkpoint inhibition with the ability to act through PD-L1 expressed on both tumor and immune cells.
Data presented at SITC (Free SITC Whitepaper) 2021 demonstrate how PD-L1 ISAC induces robust, target-dependent activation of the immune system, including induction of immunological memory.
Treatment with PD-L1 ISACs led to an effective anti-tumor response that was substantially improved over PD-L1 antibody blockage in preclinical models.
Poster #862: "Dectin-2, a novel target for tumor macrophage reprogramming in cancer immunotherapy"
Presenter: Justin A. Kenkel, Ph.D.
Details: Saturday, Nov. 13, 2021, 7:00 a.m. – 8:30 p.m. EST, Poster Hall

Key findings from the study:
For the first time, Bolt Biotherapeutics is presenting data providing preclinical validation of Dectin-2, formerly referred to as TAM1, as a novel target for cancer immunotherapy. Expressed by tumor-associated macrophages (TAMs), Dectin-2 is a pattern recognition receptor that stimulates proinflammatory cytokine production and antigen presentation to drive innate and adaptive immune responses.

Findings reported at SITC (Free SITC Whitepaper) 2021 demonstrate that agonism of Dectin-2 on TAMs elicits secretion of pro-inflammatory cytokines and chemokines capable of invoking productive anti-tumor immunity.
In murine tumor models, Dectin-2 agonism mediates anti-tumor efficacy in a CD8 T cell-dependent manner and induces immunological memory against the tumor.
Bolt Biotherapeutics scientists have generated Dectin-2 agonist antibodies that show the potential to reprogram tumor-supportive macrophages into tumor-destructive macrophages.
About the Boltbody Immune-Stimulating Antibody Conjugate (ISAC) Platform
ISACs are a new category of immunotherapy that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. Boltbody ISACs comprise three primary components: a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant to activate the patient’s innate immune system. By initially targeting a single marker on the surface of a patient’s tumor cells, an ISAC can create a new immune response by activating and recruiting myeloid cells. The activated myeloid cells start a feed-forward loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This reprograms the tumor microenvironment and invokes an adaptive immune response that targets the tumor, with the goal of durable responses for patients with cancer.