Company: BOLT
Filing Date: 2025-03-24
Form Type: 10-K
Source: 0000950170-25-043873
Chunk: 11

Company: Bolt Biotherapeutics, Inc.
Filing Date: 2025-03-24
Form: 10-K
Item: Item 1
Chunk 11
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 targets claudin 18.2, which is overexpressed in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. Selection of BDC-4182 as our clinical candidate was supported by preclinical experiments demonstrating potent anti-tumor activity in multiple preclinical models, safety and tolerability in non-human primates, and enhanced preclinical efficacy compared to cytotoxic ADCs in murine tumor models. Data on our claudin 18.2 Boltbody ISAC program were presented at the Society for Immunotherapy of Cancer’s (SITC) Annual Meetings in both November of 2024 and 2023. We expect to initiate our first in human clinical trial with BDC-4182 in the second quarter 2025. We secured exclusive worldwide rights to BDC-4182 following the restructuring of the Innovent collaboration in March 2024. Innovent and its affiliates are eligible to receive commercial and sales milestone payments as well as royalties on global net sales. 

We have two additional ISAC programs utilizing our next-generation Boltbody ISAC technology platform in preclinical development. One is a Boltbody ISAC targeting carcinoembryonic antigen cell adhesion molecule 5, or CEA. CEA is a well-known tumor antigen expressed in various solid tumors including, colorectal, non-small cell lung, pancreatic, and breast. CEA is upregulated on the cell surface of these cancers. CEA allows us to target these cancers, some of which are immunologically “cold.” In our preclinical studies, we have observed promising in vitro and in vivo activity with notable anti-tumor activity, including complete tumor regression and immunological memory. 

Our final Boltbody ISAC program targets PD-L1. Patients with tumors that are nonresponsive or become refractory to immune checkpoint blockade have few treatment options. PD-L1 is an immune checkpoint protein that can be expressed on cancer, including cancers such as lung, colorectal, and breast, and on immune cells. Expression of PD-L1 on these cells engages the PD-1 checkpoint and results in the inhibition of a productive anti-tumor immune response. More specifically, T cell-mediated immune responses are significantly dampened since the expression of PD-L1 on the cancer cells engages with the PD-1 on the cell surface of T cells and acts like a brake on the immune system. Inhibition of the PD-L1/PD-1 axis has shown potent anti-tumor immune responses in numerous types of cancers; however