trastuzumab imbotolimod (BDC-1001) / Bolt Biotherapeutics - LARVOL DELTA

Bolt Biotherapeutics Reports First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "Research and Development (R&D) Expenses – R&D expenses were $9.5 million for the quarter ended March 31, 2025, compared to $16.5 million for the same quarter in 2024. The decrease between the comparable periods was mainly due to a decrease in salary and related expenses, a decrease in clinical expenses primarily related to the discontinued development of trastuzumab imbotolimod, formerly known as BDC-1001 in May 2024."

Commercial • Endometrial Cancer • Gastrointestinal Cancer • HER2 Positive Breast Cancer

BBI-20201001: A First-in-human Study Using BDC-1001 As a Single Agent and in Combination with Nivolumab in Advanced HER2-Expressing Solid Tumors (clinicaltrials.gov) - P1/2 | N=175 | Terminated | Sponsor: Bolt Biotherapeutics, Inc. | Trial completion date: Jan 2026 ➔ Feb 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jan 2025 ➔ Oct 2024; Sponsor Decision

Trial completion date • Trial primary completion date • Trial termination • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

BBI-20231001: Trial of BDC-1001 +/- Pertuzumab in Subjects with HER2-Positive Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=11 | Terminated | Sponsor: Bolt Biotherapeutics, Inc. | Trial completion date: Mar 2025 ➔ Sep 2024 | Active, not recruiting ➔ Terminated; Sponsor Decision

Trial completion date • Trial termination • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Key learnings from BDC-1001 phase 1 FIH dose escalation trial inform next-generation ISACs (SITC 2024) - P1/2 | "The study was conducted in compliance with the Declaration of Helsinki and International Conference on Harmonization Guidelines for Good Clinical Practice. All patients provided written informed consent."

IO biomarker • P1 data • Oncology • HER-2 • TNFA

Bolt Biotherapeutics Presents...Key Learnings from Phase 1 Dose-Escalation Trial of BDC-1001 at SITC 39th Annual Meeting (GlobeNewswire) - P1/2 | N=175 | NCT04278144 | Sponsor: Bolt Biotherapeutics, Inc. | "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 was associated with clinical benefit; Pharmacodynamic changes were observed in HER2 IHC3+ and HER2 IHC2+, with both the greatest increase and statistical significance 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."

P1 data • Oncology • Solid Tumor

BBI-20201001: A First-in-human Study Using BDC-1001 as a Single Agent and in Combination With Nivolumab in Advanced HER2-Expressing Solid Tumors (clinicaltrials.gov) - P1/2 | N=175 | Active, not recruiting | Sponsor: Bolt Biotherapeutics, Inc. | N=390 ➔ 175 | Trial completion date: Oct 2026 ➔ Jan 2026

Combination therapy • Enrollment change • Metastases • Trial completion date • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

BBI-20231001: Trial of BDC-1001 +/- Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=11 | Active, not recruiting | Sponsor: Bolt Biotherapeutics, Inc. | N=66 ➔ 11

Combination therapy • Enrollment change • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Phase 2 study of novel HER2-targeting, TLR7/8 immune-stimulating antibody conjugate (ISAC) BDC-1001 (trastuzumab imbotolimod) +/- pertuzumab (P) in patients (pts) with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab deruxtecan (T-DXd). (ASCO 2024) - P2 | "Li B, et al. ASCO 2023, Abstract 2538."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • TLR7

BBI-20231001: Trial of BDC-1001 +/- Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=66 | Active, not recruiting | Sponsor: Bolt Biotherapeutics, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

BBI-20201001: A First-in-human Study Using BDC-1001 as a Single Agent and in Combination With Nivolumab in Advanced HER2-Expressing Solid Tumors (clinicaltrials.gov) - P1/2 | N=390 | Active, not recruiting | Sponsor: Bolt Biotherapeutics, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Metastases • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Bolt Biotherapeutics Reports First Quarter 2024 Results, Announces Strategic Pipeline Prioritization and Changes to Leadership Team (GlobeNewswire) - "BDC-3042 Phase 1 dose escalation continues to advance....Bolt anticipates providing an update on enrollment and safety in the second half of the year; Discontinued development of trastuzumab imbotolimod (BDC-1001). Following a strategic review, Bolt has determined that the program will not meet its pre-defined success criteria, and Bolt will therefore be focusing resources on its next-generation ISAC programs."

Discontinued • Enrollment status • P1 data • Oncology • Solid Tumor

Bolt Biotherapeutics Reports Fourth Quarter and Full-Year 2023 Financial Results and Provides Business Update (GlobeNewswire) - "We have now administered BDC-1001, which we have renamed trastuzumab imbotolimod, to patients in all five of the Phase 2 cohorts. BDC-3042 also continues to advance, and has now entered the fourth dose escalation cohort without a dose-limiting toxicity. Both clinical programs are on track and we look forward to providing updates later this year."

P1/2 data • P2 data • Trial status • Colorectal Cancer • Endometrial Cancer • Gastroesophageal Cancer • HER2 Positive Breast Cancer

Phase 2 study of novel HER2-targeting, TLR7/8 immune-stimulating antibody conjugate (ISAC) BDC-1001 +/- pertuzumab in patients with HER2-positive metastatic breast cancer (MBC) previously treated with trastuzumab deruxtecan (SABCS 2023) - P1/2 | "This study is expected to initiate accrual in 2H 2023. For additional information, please contact Bolt Biotherapeutics at 1-650-665-9295 or info@boltbio.com."

Clinical • Metastases • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • TLR7

Investigators Will Assess BDC-1001.S/Pertuzumab in HER2+ Breast Cancer (Cancer Network) - "Investigators will evaluate the anti-tumor activity of BDC-1001.S, an immune-stimulating antibody conjugate (ISAC), with or without pertuzumab (Perjeta) in patients with HER2-positive breast adenocarcinoma and other HER2-expressing cancers in a phase 2 trial (NCT05954143), according to data from a poster presented at 2023 San Antonio Breast Cancer Symposium (SABCS)....The phase 2 trial is an open-label, multicenter study, and patients with HER2-positive metastatic breast cancer will be randomly assigned into 2 arms. The first arm will receive single agent BDC-1001 intravenously (IV) every 2 weeks at the arrived dose of 20 mg/kg, which was based on safety, clinical efficacy, and pharmacokinetics reported from the phase 1 trial. The second arm will receive the same dose of BDC-1001 IV every 2 weeks in combination with an 840 mg/420 mg dose of pertuzumab IV, which is administered every 3 weeks."

Clinical protocol • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology

Bolt Biotherapeutics Enrolls First Patient in Phase 2 Clinical Study Evaluating BDC-1001 in Patients with HER2-Positive Breast Cancer Previously Treated with Enhertu (GlobeNewswire) - "Bolt Biotherapeutics, Inc...today announced that the first patient has been dosed in the Phase 2 clinical trial investigating BDC-1001, a HER2-targeting Boltbody Immune-Stimulating Antibody Conjugate (ISAC), as a single agent and in combination with the HER2-targeting antibody pertuzumab....A poster detailing the trial design and rationale will also be presented at the 2023 San Antonio Breast Cancer Symposium on Wednesday, December 6, 2023."

Clinical protocol • Trial status • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

The combination of a trastuzumab ISAC and pertuzumab augments anti-tumor efficacy in multiple HER2+ tumor models relative to trastuzumab plus pertuzumab (SITC 2023) - "These studies suggest that this combination may enhance the clinical activity of trastuzumab-based ISACs. This hypothesis is being assessed in a randomized Phase 2 clinical trial with BDC-1001 and pertuzumab in patients with HER2+ breast cancer post trastuzumab deruxtecan (BBI-20231001)."

Preclinical • Breast Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • FCGR2A • HER-2

Phase 2 study of the HER2-targeting TLR7/8 immune stimulating antibody conjugate (ISAC) BDC-1001 monotherapy +/- nivolumab in patients with HER2+ colorectal, endometrial, or gastroesophageal cancer (SITC 2023) - P1/2 | "Exploratory objectives will be pharmacodynamic biomarkers in tumor tissue and in peripheral blood, to help elucidate the mechanism of action and identify biomarkers associated with BDC-1001’s biological activity. Enrollment is ongoing in the United States, Europe, and South Korea"

Clinical • Monotherapy • P2 data • Esophageal Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • HER-2 • TLR7

Recommended phase II 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 (ESMO 2023) - P1/2 | "BDC-1001 was given IV q3w, q2w, or q1w as monotherapy (mono; n=94) and q2w or q1w with nivolumab 240mg q2w (combo; n=37). Conclusions Our novel ISAC BDC-1001 (mono/combo) led to tolerable, encouraging efficacy, translational biomarker data consistent with novel MOA in pts with pretreated HER2+ tumors, particularly at the 20mg/kg q2w RP2D. International phase 2 expansions in HER2+ colorectal, gastroesophageal, and endometrial cancers and a new phase 2 in breast cancer (BDC-1001 ± pertuzumab) have been initiated."

Clinical • Metastases • P1 data • P2 data • PK/PD data • Breast Cancer • Endometrial Cancer • HER2 Breast Cancer • Oncology • Solid Tumor • HER-2 • IFNG

Bolt Biotherapeutics Presents Updated Clinical Data from Phase 1 Dose-Escalation Trial of BDC-1001 as Monotherapy and in Combination with Nivolumab in HER2-Expressing Tumors at ESMO 2023 Congress (GlobeNewswire) - P1/2 | N=390 | NCT04278144 | Sponsor: Bolt Biotherapeutics, Inc. | "Bolt Biotherapeutics...presented updated data from its Phase 1 dose-escalation trial of BDC-1001 at the European Society for Medical Oncology (ESMO) 2023 Congress....'We look forward to presenting initial data from the Phase 2 dose-expansion trial in 2024'....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%)."

P1/2 data • Biliary Tract Cancer • Colorectal Cancer • Ovarian Cancer

Bolt Biotherapeutics to Present Data at the Society for Immunotherapy of Cancer’s 2023 Annual Meeting (GlobeNewswire) - "Bolt Biotherapeutics...announced that it will present four posters at the Society for Immunotherapy of Cancer (SITC) 38th Annual Meeting. The conference is being held at the San Diego Convention Center in San Diego, Calif. and virtually from November 1-5, 2023....'Our research team has made significant progress across our portfolio, highlighting our commitment to generate breakthroughs for patients. In addition to clinical-stage data that further validate our Boltbody™ ISAC technology, we are excited to show at SITC for the first time our preclinical work with a trastuzumab ISAC and pertuzumab and how the combination augments anti-tumor efficacy in multiple HER2+ tumor models relative to trastuzumab plus pertuzumab'."

Preclinical • Trial status • Colorectal Cancer • Endometrial Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Kidney Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Renal Cell Carcinoma • Solid Tumor

Bolt Biotherapeutics to Present New Clinical Data from Completed Phase 1/2 Dose-Escalation Trial of BDC-1001 in HER2-Expressing Solid Tumors at the ESMO Congress 2023 (GlobeNewswire) - "Bolt Biotherapeutics, Inc...announced that updated clinical data from its Phase 1/2 dose-escalation study of BDC-1001 will be presented in a mini-oral presentation at the European Society for Medical Oncology (ESMO) Congress 2023, being held in Madrid, Spain and virtually from October 20-24, 2023....The ESMO presentation will include new results from the recently completed first-in-human Phase 1/2 dose-escalation study of BDC-1001 in patients with advanced HER2-expressing solid tumors."

P1/2 data • PK/PD data • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Solid Tumor

Bolt Biotherapeutics Receives Orphan Drug Designation for BDC-1001 for Treatment of Gastric Cancers (GlobeNewswire) - "Bolt Biotherapeutics...announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation for BDC-1001 for the treatment of gastric cancer, including gastroesophageal junction cancer."

Orphan drug • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma

Orphan Designation: Treatment of gastric cancer, including gastroesophageal junction cancer (FDA) - Date Designated: 09/22/2023

Orphan drug • Gastric Cancer • Gastroesophageal Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Trial of BDC-1001 +/- Pertuzumab in Subjects With HER2-Positive Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=66 | Recruiting | Sponsor: Bolt Biotherapeutics, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Bolt Biotherapeutics Reports Second Quarter 2023 Financial Results and Provides Business Update (GlobeNewswire) - "R&D expenses were $15.6 million for the quarter ended June 30, 2023, compared to $18.9 million for the same quarter in 2022. The decrease in R&D expenses was due to lower manufacturing expenses related to the timing of batch production of our product candidates and lower lab supplies and contract service expenses, offset by higher clinical expenses related to the ongoing BDC-1001 clinical trial."

Commercial • Breast Cancer • Colorectal Cancer • Endometrial Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Gynecologic Cancers • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor