• BDC-1001 elicited objective clinical responses, including multiple PRs and long-term stable disease, across a diverse set of solid tumor types in monotherapy and in combination with nivolumab
  • Data support selection of a recommended Phase 2 dose and advancement into Phase 2 studies in breast, colorectal, endometrial, and gastroesophageal cancers
  • Entered into a new collaboration with Roche, as part of further BDC-1001 Phase 2 program expansion, supplying pertuzumab (Perjeta®) to evaluate in combination with BDC-1001

REDWOOD CITY, CA, USA I March 29, 2023 I Bolt Biotherapeutics, Inc. (Nasdaq: BOLT), a clinical-stage biopharmaceutical company pioneering novel immuno-oncology therapeutics for the treatment of cancer, today reported positive topline data from the company’s recently completed dose-escalation study of BDC-1001 in HER2-expressing solid tumors that support advancing into two Phase 2 studies. BDC-1001 is an investigational Immune-Stimulating Antibody Conjugate (ISAC) in development for the treatment of patients with HER2-expressing cancer. Data will be presented at an upcoming medical meeting.

Topline findings from this trial indicate that BDC-1001 was well tolerated at all dose levels and schedules evaluated, both as monotherapy and in combination with nivolumab. Target drug exposure levels were achieved at or near the recommended Phase 2 dose (RP2D) by more frequent administration including every other week (q2w) and weekly (q1w) administration schedules. Anti-tumor activity was observed in the form of multiple partial responses (PRs), tumor shrinkage, and long-term stable disease at or near the RP2D across multiple HER2-expressing solid tumor types in monotherapy and in combination with nivolumab. Moreover, biomarker data demonstrate that corresponding clinical and safety data are related to the ISAC mechanism. These data support the selection of a RP2D and advancement to Phase 2 studies.

“We are enthusiastic to be taking the next step in investigating the therapeutic promise of BDC-1001. In the study, we not only achieved target exposure levels for BDC-1001, but at those levels we saw promising signs of clinical activity as a single agent and in combination with nivolumab,” said Edith A. Perez, M.D., Chief Medical Officer of Bolt Biotherapeutics. “We look forward to sharing full data at an upcoming major medical conference, and to initiating a focused Phase 2 program working with a diverse group of investigators in the U.S. and internationally. I’d like to express my gratitude to all the patients and investigators who are participating in our trial and to the incredible team at Bolt for their hard work and dedication.”

“While we have made remarkable progress in developing new treatments for patients with HER2-expressing cancers, there remains an urgent need for innovation,” said Bob T. Li, M.D., Ph.D., MPH, medical oncologist, and principal investigator at Memorial Sloan Kettering Cancer Center (MSK). “In this international dose-escalation trial, BDC-1001 leveraged a novel mechanism of HER2-targeted immune stimulating antibody conjugate and demonstrated encouraging evidence of efficacy and manageable safety, providing hope of a potential new treatment option for patients with HER2-expressing tumors.”

Bolt Biotherapeutics’ Phase 1 dose-escalation trial enrolled more than 100 patients with 16 different HER2-expressing solid tumor types. 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.

New Agreement with Roche Supporting Phase 2 Study
Bolt Biotherapeutics also announced today that it has entered into a clinical supply agreement with Roche to evaluate pertuzumab (Perjeta®) in combination with BDC-1001. Through a supply agreement, Roche will provide pertuzumab in support of a Phase 2 metastatic breast cancer trial.

Preclinical research combining pertuzumab with a BDC-1001-surrogate demonstrated enhanced anti-tumor efficacy in multiple models and a compelling mechanistic rationale for conducting a clinical trial to evaluate a potential impact on patients. Pertuzumab, which binds a distinct HER2 epitope from the trastuzumab component of BDC-1001, may increase the amount of clustered Fc or “eat me signals” on the surface of the tumor. This appears to trigger enhanced antibody-dependent cellular phagocytosis, a key element of the BDC-1001 mechanism of action, resulting in further propagation of BDC-1001-driven immune activation and anti-tumor efficacy.

BDC-1001 Phase 2 Clinical Program
Bolt’s Phase 2 clinical plan includes two distinct studies, each using a Simon two-stage design. These studies will build upon Bolt’s existing clinical sites and clinical trial centers of excellence in the U.S. and South Korea, expanding into multiple countries in Europe, and include:

  • Phase 2 dose expansions of the current Phase 1/2 trial will initially focus on investigating BDC-1001 as a monotherapy, given the positive single-agent clinical data seen in the Phase 1 trial, enrolling HER2-positive colorectal, endometrial, and gastroesophageal cancer patients. Combination arms with nivolumab are expected to initiate in each indication following demonstration of monotherapy anti-tumor activity. Bristol Myers Squibb, Bolt’s clinical collaborator for this study, will continue to supply nivolumab at no cost for such expansion cohorts.
  • Initiation of a two-cohort Phase 2 clinical trial exploring BDC-1001 as monotherapy and BDC-1001 in combination with pertuzumab in patients with HER2-positive metastatic breast cancer who have developed tumor progression following treatment with Enhertu.

About the Boltbody™ Immune-Stimulating Antibody Conjugate (ISAC) Platform
Bolt Biotherapeutics’ Boltbody ISAC platform unites 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 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-1001, a HER2-targeting Boltbody Immune-Stimulating Antibody Conjugate (ISAC), BDC-3042, a myeloid-modulating antibody, and multiple Boltbody ISAC collaboration programs. BDC-1001 has completed a Phase 1 dose-escalation study demonstrating tolerability and early clinical efficacy, and the Company plans to initiate Phase 2 studies in 2023. Bolt Biotherapeutics is advancing BDC-3042, an agonist antibody targeting Dectin-2, through IND-enabling activities and expects to initiate a Phase 1 trial in the second half of 2023. In preclinical development, BDC-3042 demonstrated the ability to convert tumor-supportive macrophages to tumor-destructive macrophages. Bolt Biotherapeutics is leveraging its ability to engineer and optimize novel applications of its Boltbody ISACs to develop multiple immuno-oncology candidates through strategic collaborations with leading biopharmaceutical companies. For more information, please visit https://www.boltbio.com/

SOURCE: Bolt Biotherapeutics