CEA-targeted ISAC elicits complete responses in mice and is well-tolerated in NHPs
PD-L1 ISAC directly activates and reprograms PD-L1-expressing myeloid cells in the TME to drive complete responses and immunological memory
REDWOOD CITY, CA, USA I April 30, 2025 I Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, today announced preclinical results from its next-generation Boltbody™ ISACs targeting CEACAM5 and PD-L1 at the American Association for Cancer Research (AACR) Annual Meeting.
“We are encouraged by these early results from our next-generation Boltbody™ ISACs targeting CEA and PD-L1,” said Michael Alonso, Ph.D., Senior Vice President of Research. “There are currently no approved therapies targeting CEA, and our next-gen CEA ISAC induced complete and durable anti-tumor responses in mice and was well-tolerated in NHPs. Additionally, the preclinical results demonstrated that PD-L1 ISACs represent a compelling new approach to treat cancer, leveraging mechanisms that are distinct from and potentially complementary to conventional PD-1/PD-L1 blockade.”
CEA refers to a specific carcinoembryonic antigen cell adhesion molecule also known as CEACAM-5 that is commonly found in gastrointestinal cancers such as colorectal cancer. Bolt’s lead CEA-targeted ISAC comprises a novel, fully human antibody with high affinity and selectivity to CEA, and not to other members of the CEACAM family, conjugated to a proprietary next-generation TLR7/8 agonist via a non-cleavable linker. This ISAC drives enhanced phagocytosis of CEA-positive tumor cells and stimulates production of critical immune-activating cytokines including IL-12p70, IFNg, and TNFa. Key results with the next-gen CEA ISAC are below:
- Antigen-dependent induction of immune-stimulating cytokines in human, NHP and mouse effector cells
- Complete responses in CEA transgenic syngeneic model demonstrates robust efficacy
- Induction of immunological memory demonstrates potential for durable responses
- In a non-GLP NHP tox study, the next-generation CEA ISAC was well-tolerated with no significant drug-related adverse events observed up to 15 mg/kg, the highest tested dose
Bolt’s PD-L1 ISAC utilizes a novel human anti-PD-L1 antibody conjugated to a next-generation TLR7/8 agonist payload via a non-cleavable linker. This ISAC leverages a unique mechanism of action due to its ability to target both tumor and immune cells that express PD-L1. 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
- Blockade of the PD-1/PD-L1 axis is not required for PD-L1 ISAC efficacy but may be a supportive mechanism and complementary combination strategy
- Favorable safety profile was demonstrated in non-GLP NHP toxicology studies supporting use in combination with SoC therapies & other agents
Details about the poster presentations can be found on the AACR website. Additionally, a copy of each poster is available on the Publications page of the Bolt Biotherapeutics website.
About the Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) Platform
Bolt Biotherapeutics’ Boltbody ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.
About Bolt Biotherapeutics, Inc.
Bolt Biotherapeutics is a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer. Bolt Biotherapeutics’ pipeline candidates are built on the Company’s deep expertise in myeloid biology and cancer drug development. The Company’s pipeline includes BDC-3042, a first-in-class agonist antibody that activates macrophages by targeting dectin-2, and BDC-4182, a next-generation Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) clinical candidate targeting claudin 18.2. BDC-3042 is currently in a Phase 1 dose escalation trial that includes patients with any of seven different solid tumor types. BDC-4182 is supported by strong in vitro and in vivo data demonstrating potent anti-tumor activity, and activities are underway to support the initiation of clinical trials in second quarter 2025. Bolt Biotherapeutics is also developing additional Boltbody™ ISACs in strategic collaborations with leading biopharmaceutical companies. For more information, please visit https://www.boltbio.com/.
SOURCE: Bolt Biotherapeutics
Post Views: 2,561
CEA-targeted ISAC elicits complete responses in mice and is well-tolerated in NHPs
PD-L1 ISAC directly activates and reprograms PD-L1-expressing myeloid cells in the TME to drive complete responses and immunological memory
REDWOOD CITY, CA, USA I April 30, 2025 I Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, today announced preclinical results from its next-generation Boltbody™ ISACs targeting CEACAM5 and PD-L1 at the American Association for Cancer Research (AACR) Annual Meeting.
“We are encouraged by these early results from our next-generation Boltbody™ ISACs targeting CEA and PD-L1,” said Michael Alonso, Ph.D., Senior Vice President of Research. “There are currently no approved therapies targeting CEA, and our next-gen CEA ISAC induced complete and durable anti-tumor responses in mice and was well-tolerated in NHPs. Additionally, the preclinical results demonstrated that PD-L1 ISACs represent a compelling new approach to treat cancer, leveraging mechanisms that are distinct from and potentially complementary to conventional PD-1/PD-L1 blockade.”
CEA refers to a specific carcinoembryonic antigen cell adhesion molecule also known as CEACAM-5 that is commonly found in gastrointestinal cancers such as colorectal cancer. Bolt’s lead CEA-targeted ISAC comprises a novel, fully human antibody with high affinity and selectivity to CEA, and not to other members of the CEACAM family, conjugated to a proprietary next-generation TLR7/8 agonist via a non-cleavable linker. This ISAC drives enhanced phagocytosis of CEA-positive tumor cells and stimulates production of critical immune-activating cytokines including IL-12p70, IFNg, and TNFa. Key results with the next-gen CEA ISAC are below:
- Antigen-dependent induction of immune-stimulating cytokines in human, NHP and mouse effector cells
- Complete responses in CEA transgenic syngeneic model demonstrates robust efficacy
- Induction of immunological memory demonstrates potential for durable responses
- In a non-GLP NHP tox study, the next-generation CEA ISAC was well-tolerated with no significant drug-related adverse events observed up to 15 mg/kg, the highest tested dose
Bolt’s PD-L1 ISAC utilizes a novel human anti-PD-L1 antibody conjugated to a next-generation TLR7/8 agonist payload via a non-cleavable linker. This ISAC leverages a unique mechanism of action due to its ability to target both tumor and immune cells that express PD-L1. 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
- Blockade of the PD-1/PD-L1 axis is not required for PD-L1 ISAC efficacy but may be a supportive mechanism and complementary combination strategy
- Favorable safety profile was demonstrated in non-GLP NHP toxicology studies supporting use in combination with SoC therapies & other agents
Details about the poster presentations can be found on the AACR website. Additionally, a copy of each poster is available on the Publications page of the Bolt Biotherapeutics website.
About the Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) Platform
Bolt Biotherapeutics’ Boltbody ISAC platform harnesses the precision of antibodies with the power of the innate and adaptive immune system to generate a productive anti-cancer response. Each Boltbody ISAC candidate comprises a tumor-targeting antibody, a non-cleavable linker, and a proprietary immune stimulant. The antibody is designed to target one or more markers on the surface of a tumor cell and the immune stimulant is designed to recruit and activate myeloid cells. Activated myeloid cells initiate a positive feedback loop by releasing cytokines and chemokines, chemical signals that attract other immune cells and lower the activation threshold for an immune response. This increases the population of activated immune system cells in the tumor microenvironment and promotes a robust immune response with the goal of generating durable therapeutic responses for patients with cancer.
About Bolt Biotherapeutics, Inc.
Bolt Biotherapeutics is a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer. Bolt Biotherapeutics’ pipeline candidates are built on the Company’s deep expertise in myeloid biology and cancer drug development. The Company’s pipeline includes BDC-3042, a first-in-class agonist antibody that activates macrophages by targeting dectin-2, and BDC-4182, a next-generation Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) clinical candidate targeting claudin 18.2. BDC-3042 is currently in a Phase 1 dose escalation trial that includes patients with any of seven different solid tumor types. BDC-4182 is supported by strong in vitro and in vivo data demonstrating potent anti-tumor activity, and activities are underway to support the initiation of clinical trials in second quarter 2025. Bolt Biotherapeutics is also developing additional Boltbody™ ISACs in strategic collaborations with leading biopharmaceutical companies. For more information, please visit https://www.boltbio.com/.
SOURCE: Bolt Biotherapeutics
Post Views: 2,561
