On November 12, 2024 Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, reported financial results for the third quarter ended September 30, 2024, and provided a business update (Press release, Bolt Biotherapeutics, NOV 12, 2024, View Source [SID1234648159]).

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"During the third quarter, we continued to make progress with our two proprietary programs, BDC-3042 and BDC-4182," said Willie Quinn, Chief Executive Officer. "We have now completed the sixth dose level in the first-in-human clinical trial of BDC-3042, have opened the final cohort which will study a dose level of 10 mg/kg, and expect to provide a data update in the first half of 2025. We are particularly excited about our next-generation ISAC BDC-4182, which builds on the lessons we learned from our clinical experience with BDC-1001. We believe that BDC-4182’s dramatic increase in potency and activity will potentially enable the treatment of patients whose tumors have lower claudin 18.2 expression and may provide even better anti-tumor activity than conventional ADCs. We presented some of the data that underlies this excitement at SITC (Free SITC Whitepaper), and the team is hard at work preparing for a clinical trial initiation of BDC-4182 in the second quarter next year."

Recent Highlights and Anticipated Milestones

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Presented updated clinical activity of BDC-4182 at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). BDC-4182 is a next-generation BoltbodyTMISAC clinical candidate targeting claudin 18.2, a novel, clinically validated target in oncology with expression in gastric/gastroesophageal junction cancer, pancreatic cancer, and other tumor types. BDC-4182 has advanced into IND-enabling activities, supported by in vitro and in vivo experiments demonstrating potent anti-tumor activity in multiple preclinical models, with clinical trial initiation expected in 2025. BDC-4182 was well tolerated in non-human primates at the highest dose tested (12mg/kg) with an acceptable safety profile. BDC-4182 outperformed cytotoxic claudin 18.2 ADCs in syngeneic models and BDC-4182’s favorable toxicology profile enables a variety of potential future combinations.

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Presented key learnings from Phase 1 dose-escalation trial of BDC-1001 at SITC (Free SITC Whitepaper). First-generation ISAC BDC-1001 demonstrated immunological activity in this first-in-human trial, particularly in patients with high HER2 antigen expression. Greater immune activation appeared to be associated with clinical benefit. Pharmacodynamic changes were observed in patients whose tumors had higher levels of HER2 and were statistically significant in patients with HER2 IHC 3+ tumors. Data supports the hypothesis that an ISAC with enhanced immune activation could offer greater efficacy, warranting further testing in next-generation ISACs.
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Advanced to cohort 7 (10 mg/kg) in the Phase 1 study of BDC-3042 in patients with advanced cancers. 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 triple-negative breast cancer (TNBC), colorectal cancer, clear cell renal cell carcinoma, head and neck cancer, non-small cell lung cancer (NSCLC), ovarian cancer, or melanoma.
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Collaborations with Genmab and Toray continue to progress. The Company continues to work with its collaborators to discover and develop ISACs for the treatment of cancer.
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Cash, cash equivalents, and marketable securities were $84.4 million as of September 30, 2024. Cash on hand is expected to fund multiple milestones and operations through mid-2026.

Third Quarter 2024 Financial Results

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Collaboration Revenue – Collaboration revenue was $1.1 million for the quarter ended September 30, 2024, compared to $2.5 million for the same quarter in 2023. Revenue in the comparative periods was generated from services performed under the R&D collaborations as we fulfill our performance obligations.

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Research and Development (R&D) Expenses – R&D expenses were $13.8 million for the quarter ended September 30, 2024, compared to $15.0 million for the same quarter in 2023. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses primarily as a result of the May 2024 restructuring partially offset by an increase in contract manufacturing expenses.

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General and Administrative (G&A) Expenses – G&A expenses were $3.8 million for the quarter ended September 30, 2024, compared to $5.8 million for the same quarter in 2023. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses primarily as a result of the May 2024 restructuring.

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Loss from Operations – Loss from operations was $16.4 million for the quarter ended September 30, 2024, compared to $18.2 million for the same quarter in 2023.

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.