• Updated safety data supports the selection of 20 mg/kg q2w as the recommended Phase 2 dose (RP2D)
  
• Improved efficacy with one partial response (PR) improving to a complete response (CR), two additional patients with long-term stable disease (SD), and three patients who have now received therapy for ≥ 1 year
• BDC-1001 continues to be well tolerated

REDWOOD CITY, Calif., Oct. 23, 2023 (GLOBE NEWSWIRE) -- Bolt Biotherapeutics (Nasdaq: BOLT), a clinical-stage biopharmaceutical company developing novel immunotherapies for the treatment of cancer, today presented updated data from its Phase 1 dose-escalation trial of BDC-1001 at the European Society for Medical Oncology (ESMO) 2023 Congress, being held in Madrid, Spain and virtually from October 20-24, 2023.

BDC-1001 is an investigational Immune-Stimulating Antibody Conjugate (ISAC) in development for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive cancer. BDC-1001 comprises a HER2-targeting biosimilar of trastuzumab conjugated with a non-cleavable linker to a proprietary TLR7/8 agonist. The Phase 1 dose-escalation trial enrolled 131 patients with 16 different HER2-expressing solid tumor types across 18 dose levels in two arms, monotherapy and in combination with nivolumab. At enrollment, all patients entered in the study had evidence of tumor progression following prior standard of care treatments, and a majority of the patients were heavily pre-treated.

“The encouraging updated Phase 1 dose escalation data of BDC-1001 that was presented at ESMO further support the initiation of our Phase 2 dose-expansion clinical trial in patients with HER2-positive colorectal, breast, endometrial and gastric cancers,” said Edith A. Perez, M.D., Chief Medical Officer of Bolt Therapeutics. “We look forward to presenting initial data from the Phase 2 dose-expansion trial in 2024.”

“The updated data from the Phase 1 dose-escalation study continue to provide clinical validation of ISACs as a potential therapeutic approach using BDC-1001 to treat patients with HER2-expressing tumors,” said Bob T. Li., M.D., Ph.D., MPH, medical oncologist, and principal investigator at Memorial Sloan Kettering Cancer Center (MSK).

Key findings from the updated Phase 1 BDC-1001 dose escalation study are summarized below.

• Improved BDC-1001 efficacy was observed since the data presented at ASCO in June 2023 with one new CR, two additional long-term SDs, and three patients who received therapy for at least one year.
• At the RP2D, one CR was observed in the monotherapy arm in a patient with salivary gland cancer and three PRs were observed at the RP2D; one in the monotherapy arm in a patient with biliary tract cancer and two in the combination arm in patients with colorectal and ovarian cancer. The response rate at the RP2D was 29% in evaluable patients with HER2-positive tumors, both in monotherapy (2/7, 29%) and in combination with nivolumab (2/7, 29%).
• At the RP2D, among evaluable patients with HER2-positive tumors, 43% (3/7) in the monotherapy arm and 57% (4/7) in the combination arm experienced at least 24 weeks of disease control, and 57% (4/7) in the monotherapy arm and 71% (5/7) in the combination arm achieved tumor shrinkage.
• BDC-1001 continues to be well tolerated at all dose levels and schedules as both monotherapy and in combination with nivolumab with no increase in toxicity in combination with BDC-1001. The most frequent drug-related treatment-emergent adverse events (TEAEs) were grade 1 or 2 infusion-related reactions, which were observed in 29.8% of subjects. Grade 3 or higher treatment-related TEAEs were seen in ten subjects (7.6%), with only one grade 4 and no grade 5 drug-related AEs.
• Pharmacodynamic responses in both plasma and tissue were consistent with the mechanism of action for an ISAC. Statistically significant upregulation of TLR signaling pathway gene signature, innate immunity gene signatures and T cell inflamed phenotype was observed in the four patients with clinical benefit. Increases in innate immunity signatures was observed in patients in the q2w cohorts, but not q1w.
• The once-weekly dosing cohorts experienced higher rates of adverse events versus every-two-week (q2w) dosing, including: grade 3 or higher BDC-1001-related TEAEs (10.0% versus 2.6%), grade 3 or higher LVEF decreases (7.5% versus 2.6%), and infusion-related reactions (40.0% versus 28.2%), providing further support for the selection of 20 mg/kg q2w as the RP2D.

Details about the presentation can be found below and on the ESMO website. Additionally, a copy of the presentation is available on the Publications page of the Bolt Therapeutics website.

• Title: Recommended phase 2 dose (RP2D) selection and pharmacodynamic (PD) data of the first-in-human immune-stimulating antibody conjugate (ISAC) BDC-1001 in patients (pts) with advanced HER2-expressing solid tumors
• Presenter: Bob Li, M.D., Ph.D., MPH, medical oncologist, and principal investigator at MSK
• Presentation number: 657MO
• Presentation session: Developmental therapeutics
• Details: Monday, October 23, 2023, 10:30 a.m. – 12:00 p.m. EDT

About BDC-1001

Bolt Biotherapeutics’ lead program, BDC-1001, is a human epidermal growth factor receptor 2 (HER2) ISAC comprising a HER2-targeting biosimilar of trastuzumab conjugated with a non-cleavable linker to a proprietary TLR7/8 agonist. Following the successful completion of the BDC-1001 dose-escalation trial for the treatment of patients with HER2-expressing solid tumors, Bolt is now conducting two Phase 2 clinical trials in the U.S., Europe, and South Korea: NCT04278144 for patients with colorectal, endometrial, and gastroesophageal cancers and NCT05954143 for patients with breast cancer.

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.

About Bolt Biotherapeutics, Inc.

Bolt Biotherapeutics is a clinical-stage biopharmaceutical company leveraging the immune system for a better way to treat cancer. The company is developing novel immunotherapies using an approach that teaches the immune system to recognize and kill cancer in a way that is immediately personalized to each patient. Its pipeline candidates are built on the Company’s deep expertise in myeloid biology and cancer drug development and include BDC-1001, a HER2-targeting Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) being evaluated in a Phase 2 trial, and BDC-3042, a myeloid-modulating agonist antibody targeting Dectin-2, being evaluated in a Phase 1 trial. Bolt Biotherapeutics is also developing multiple Boltbody™ ISACs in strategic collaborations with leading biopharmaceutical companies. For more information, please visit https://www.boltbio.com/.

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