On November 9, 2023 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, 2023, and provided an update on the continued advancement of its clinical programs (Press release, Bolt Biotherapeutics, NOV 9, 2023, View Source [SID1234637353]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"During the quarter, we continued to advance our proprietary clinical stage development programs, BDC-1001 and BDC-3042," said Randall Schatzman, Ph.D., Chief Executive Officer. "Updated Phase 1 data on BDC-1001 presented at this year’s ESMO (Free ESMO Whitepaper) Congress demonstrated improved efficacy, including our first complete response, and longer durability. We also recently received Orphan Drug Designation from the FDA for BDC-1001 in gastric cancers, one of the four types of cancer we are exploring in our BDC-1001 Phase 2 program. We look forward to presenting initial data from these Phase 2 trials in 2024."

"In addition, we administered BDC-3042 to the first patient in our first-in-human Phase 1/2 clinical study evaluating BDC-3042 in patients with six different types of solid tumors. As we approach the end of the year, we are encouraged by the continued progress in our research and clinical studies and look forward to generating breakthroughs for patients in need of new treatment options that work with the person’s body, not against it."

Recent Highlights and Anticipated Milestones

•
Updated clinical data from Phase 1 dose-escalation trial of BDC-1001 in HER2-expressing solid tumors presented at the ESMO (Free ESMO Whitepaper) 2023 Congress in October 2023. The presentation was given by Bob T. Li, M.D., Ph.D., MPH, medical oncologist and principal investigator at Memorial Sloan Kettering Cancer Center (MSK). Improvements in BDC-1001 efficacy were observed since the data presented at ASCO (Free ASCO Whitepaper) in June 2023, including one new complete response (CR) observed in the monotherapy arm. BDC-1001 achieved a 29% objective response rate (ORR) in evaluable patients with HER2-positive tumors as monotherapy as well as a 29% ORR in combination with nivolumab at the recommended Phase 2 dose (RP2D). BDC-1001 was extremely well tolerated, with no Grade 5 treatment-related treatment-emergent adverse events (TEAEs), 1 Grade 4 TEAE (1%), and 9 Grade 3 TEAEs (7%). The most common TEAE was Grade 1 or 2 infusion-related reactions, which were seen in 30% of patients in the study. BDC-1001 upregulated gene signatures of an innate and adaptive immune response in clinical responders, providing support for the immune mechanism of action of our ISAC technology. The data also provided support for the every-other week (q2w) dosing schedule by demonstrating that innate and adaptive immune gene signatures were increased in patients dosed q2w.
•
First patient administered BDC-3042 in Phase 1 study of patients with advanced cancers in October 2023. 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 will evaluate 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), or ovarian cancer.
•
Received Orphan Drug Designation for BDC-1001 for the treatment of gastric cancers in September 2023. The Office of Orphan Products Development of FDA grants Orphan Drug Designation to drugs and biologics intended for the treatment, diagnosis, or prevention of rare diseases, or conditions affecting fewer than 200,000 people in the United States. The designation affords Bolt the potential for certain benefits, including up to seven years of post-approval market exclusivity, assistance in the drug development process, tax credits for clinical development, and exemptions from certain FDA fees.
•
Presented four posters at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 38th Annual Meeting in November 2023. In the presentations, we shared preclinical data illustrating the benefits of combining BDC-1001 with the anti-HER2 antibody pertuzumab, along with trial-in-progress updates for BDC-1001 and BDC-3042. We also debuted our Claudin 18.2 ISAC program for the first time, demonstrating anti-tumor activity in multiple preclinical models.
•
Announced issuance of U.S. patent covering Dectin-2-targeting agonist antibodies, including BDC-3042 in September 2023. This patent covers antibodies with a novel mechanism of action that leverages Dectin-2 agonism to repolarize tumor-associated macrophages into immunostimulatory, anti-tumor macrophages. The claims of the patent will be valid through May 2041, excluding any patent term adjustments or extensions which may provide additional protection.
•
Cash, cash equivalents, and marketable securities were $141.4 million as of September 30, 2023. Cash on hand is expected to fund multiple milestones and operations through 2025.

Third Quarter 2023 Financial Results

•
Collaboration Revenue – Collaboration revenue was $2.5 million for the quarter ended September 30, 2023, compared to $2.1 million for the same quarter in 2022. Revenue in the comparative periods were generated from the services performed under the R&D collaborations as we fulfill our performance obligations.

•
Research and Development (R&D) Expenses – R&D expenses were $15.0 million for the quarter ended September 30, 2023, compared to $19.0 million for the same quarter in 2022. The decrease in R&D expenses was due to lower manufacturing expenses primarily related to the timing of batch production of our product candidates and lower clinical expenses due to lower site and patient costs, offset by higher contract service expenses and salary and related expenses.

•
General and Administrative (G&A) Expenses – G&A expenses were $5.8 million for the quarter ended September 30, 2023, compared to $5.5 million for the same quarter in 2022.

•
Loss from Operations – Loss from operations was $18.2 million for the quarter ended September 30, 2023, compared to $22.3 million for the same quarter in 2022. This is in part a reflection of proactive cost-containment measures taken in June 2022.

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 reprogram the tumor microenvironment 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.