BB-1701 / BlissBio - LARVOL DELTA

A first-in-human, open label, multiple dose, dose escalation, and cohort expansion phase I study to investigate the safety, tolerability, pharmacokinetics and antitumor activity of BB-1701 in patients with locally advanced/metastatic HER2-expressing solid tumors. (ASCO 2023) - P1 | "Background: BB-1701 is an antibody-drug conjugate consisting of a humanized IgG1κ monoclonal antibody and eribulin. BB-1701 was generally well tolerated up to 2.6 mg/kg dose levels and has shown promising antitumor activity in patients with HER2-overexpression solid tumors. Clinical trial information: NCT04257110."

Clinical • Metastases • P1 data • PK/PD data • Anemia • Breast Cancer • Colorectal Cancer • Dyslipidemia • Esophageal Cancer • Gallbladder Cancer • Gastric Cancer • Gastrointestinal Cancer • Hematological Disorders • Hepatology • HER2 Breast Cancer • Hypertriglyceridemia • Infectious Disease • Interstitial Lung Disease • Oncology • Ovarian Cancer • Pain • Pulmonary Disease • Respiratory Diseases • Septic Shock • Solid Tumor • CTSB • HER-2

An open-label, multicenter, phase 2 study to evaluate the safety and efficacy of BB-1701, a novel antibody drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2), in previously treated patients with HER2-positive (HER2+) or HER2-low unresectable or metastatic breast cancer (BC). (ASCO 2024) - P2 | "BB-1701 is an ADC consisting of a monoclonal antibody targeting HER2 with eribulin (microtubule inhibitor) as a payload that is capable of exerting a bystander effect...Randomization will be stratified by HER2 status (HER2+ vs. HER2-low) documented prior to T-DXd treatment...In both study parts, exploratory objectives will include evaluation of biomarkers of response to BB-1701 and BB-1701 immunogenicity; other efficacy measures (i.e., PFS on the next line of therapy) and population pharmacokinetics will be analyzed in the dose-expansion part only. Pt enrollment is currently open."

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

An open-label, multicenter, phase II study to evaluate the safety and efficacy of BB-1701, a novel antibody drug conjugate (ADC) targeting HER2, in previously treated patients (pts) with HER2+ or HER2-low unresectable or metastatic (M) breast cancer (BC) (ESMO 2024) - P2 | "Background: Treatment options for pts with unresectable/MBC have improved with targeted therapies such as trastuzumab deruxtecan (T-DXd), a HER2-directed ADC...BB-1701 is a HER2-directed ADC with eribulin (microtubule inhibitor) as a payload...In both study parts, exploratory objectives will evaluate biomarkers expression and BB-1701 immunogenicity; other efficacy measures (ie, PFS on next-line of therapy) will be analyzed in the dose expansion only. As of April 30, 2024, 6 pts were screened; 4 have been randomized."

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

A First-in-human Study of Multiple Doses of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors (clinicaltrials.gov) - P1 | N=208 | Recruiting | Sponsor: Bliss Biopharmaceutical (Hangzhou) Co., Ltd | N=88 ➔ 208 | Trial completion date: Feb 2022 ➔ Dec 2023 | Trial primary completion date: Feb 2022 ➔ Aug 2023

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

A phase II study to evaluate the safety and efficacy of BB-1701 in combination with sintilimab in patients with HER2 expression or mutation in locally advanced/metastatic breast cancer or NSCLC. (ASCO 2026) - P | "Clinical Trial Registration Number: CTR20241422 Background: BB-1701, a HER2-targeting antibody-drug conjugate (ADC) containing eribulin, has demonstrated promising antitumor activity in the clinical studies in breast cancer (BC) patients with HER2 low expression and non-small cell lung cancer (NSCLC) patients with HER2 mutation. BB-1701 in combination with Sintilimab shows encouraging antitumor activity and a manageable safety profile in HER2 low-expressing BC patients and HER2 mutated NSCLC patients. The further dose expansion study is guaranteed based on the preliminary data from dose escalation study."

Clinical • Combination therapy • IO biomarker • Metastases • P2 data • Breast Cancer • Dyslipidemia • HER2 Breast Cancer • HER2 Positive Breast Cancer • Infectious Disease • Lung Cancer • Metabolic Disorders • Nephrology • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • HER-2

BB-1701-G000-205: A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=56 | Completed | Sponsor: Eisai Inc. | Active, not recruiting ➔ Completed | N=135 ➔ 56 | Trial completion date: Mar 2027 ➔ Mar 2026 | Trial primary completion date: Mar 2027 ➔ Mar 2026

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

BB-1701-G000-205: A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=135 | Active, not recruiting | Sponsor: Eisai Inc. | Trial completion date: Mar 2026 ➔ Mar 2027 | Trial primary completion date: Feb 2025 ➔ Mar 2027

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Therapeutic Strategies to Overcome Payload Resistance of Trastuzumab Deruxtecan in HER2-Positive Cancers. (PubMed, Cancer Sci) - "Moreover, BB-1701, a novel HER2-ADC containing eribulin as a payload, to which N87 AR cells are sensitive, exhibited antitumor effects in N87 AR cells in vitro and in vivo. These findings indicate that ABC transporter-mediated drug efflux is an important mechanism underlying T-DXd resistance in HER2-positive gastric and lung cancer models. Furthermore, our study suggests that both targeting drug efflux pathways and utilizing alternative payloads may be effective strategies for overcoming T-DXd resistance in HER2-positive gastric and lung cancers."

Journal • Brain Cancer • Breast Cancer • Gastric Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ABCB1 • ABCG2 • HER-2

A First-in-human Study of Multiple Doses of BB-1701 in Subjects With Locally Advanced/Metastatic HER2 Expressing Solid Tumors (clinicaltrials.gov) - P1 | N=117 | Completed | Sponsor: Bliss Biopharmaceutical (Hangzhou) Co., Ltd | Active, not recruiting ➔ Completed | N=208 ➔ 117

Enrollment change • Trial completion • Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

A phase II study to evaluate the safety and efficacy of BB-1701 in subjects with HER2 expression locally advanced/metastatic breast cancer previously treated with HER2-ADC containing TOP-I inhibitor. (ASCO 2025) - P | "Funded by No funding sources reported Clinical Trial Registration Number: CTR20241422 Background: BB-1701 is an HER2-targeting antibody-drug conjugate (ADC) containing eribulin...Among 8 HER2 low-expressioning (IHC 1+) patients, 3 patients achieved PR (2 patients received prior trastuzumab deruxtecan and 1 patient received prior SHR-A1811) and 4 patients had SD with DCR of 87.5%. BB-1701 shows promising antitumor activity and a manageable safety profile in HER2 expressing breast cancer patients who had previously been treated with HER2-ADC (containing TOP-I inhibitor)."

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

BB-1701-G000-205: A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=135 | Active, not recruiting | Sponsor: Eisai Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Mar 2026 ➔ Feb 2025

Enrollment closed • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Eisai's abandoned Enhertu challenger set to live on at BlissBio (FierceBiotech) - "BB-1701 has survived Eisai’s decision not to option the HER2-directed antibody-drug conjugate. Weeks after Eisai quietly made its choice, its liquid biopsy partner has revealed Bliss Biopharmaceutical plans to progress the program independently...The partners went on to report responses in solid tumors, including in breast cancer patients who had previously received another anti-HER2 ADC. Yet, last month, Eisai revealed (PDF) it had decided not to exercise its BB-1701 option."

Commercial • Breast Cancer • Solid Tumor

Results of Eisai Phase 2 pilot study (Yahoo Finance) - P2 | N=135 | NCT06188559 | Sponsor: Eisai Inc. | "ANGLE provided CTC analysis with its Parsortix-based HER2 assay to assess breast cancer patients' HER2...status in a Phase 2 study of the HER2 targeting antibody-drug conjugate (HER2-ADC) BB-1701. Detailed analysis of the results demonstrates that...significant differences in HER2 CTC status and numbers of CTCs and CTC clusters were observed between the results for two different timepoints for the same patient before and after treatment...This data is highly significant as it validates that ANGLE's HER2 assay is capable of measuring changes in HER2 status over time, which is not possible with a tissue biopsy as it is an invasive procedure which cannot always be repeated."

Diagnostic • P2 data • Breast Cancer • HER2 Positive Breast Cancer

Preclinical anti-tumor activity of BB-1701, a HER2-targeting eribulin conjugated ADC, in HER2-low breast cancer PDx models. (SABCS 2024) - P2 | "Recently, the clinical landscape of HER2-low BC has changed with the approval of a HER2 targeting antibody-drug conjugate (ADC), trastuzumab-deruxtecan (T-DXd). These results indicate that BB-1701 has the potential to provide clinical benefit to HER2-low BC patients. A phase 2 clinical trial in patients with HER2 positive or HER2-low unresectable or metastatic BC is ongoing (NCT06188559)."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CTSB • HER-2

Characterization and anti-tumor activity of BB-1701, a HER2-targeting eribulin-conjugated ADC, in preclinical models [WITHDRAWN] (SABCS 2024) - No abstract available

Preclinical • Breast Cancer • Oncology • HER-2

BB-1701-G000-205: A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Eisai Inc. | Trial completion date: Oct 2026 ➔ Mar 2026 | Trial primary completion date: Oct 2026 ➔ Mar 2026

Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

A phase II study to evaluate the efficacy and safety of BB-1701 in advanced or metastatic NSCLC patients with HER2 mutation/amplification (ESMO 2024) - "Background: BB-1701 is an antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 antibody and eribulin. BB-1701 has demonstrated promising antitumor activity and a manageable safety profile in patients with HER2 mutant/amplified NSCLC."

Clinical • Metastases • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTSB • HER-2

Eisai Accelerates Progress in Oncology Research with New Data at ESMO Congress 2024… (PRNewswire) - "Research from Eisai's pipeline includes a quality-of-life analysis from the Phase 3 EMERALD study in Japan evaluating either Eisai's eribulin mesylate (HALAVEN) or a taxane in combination with trastuzumab and pertuzumab in patients with HER2-positive, locally advanced or metastatic breast cancer (NCT03264547; Presentation: #373P); findings from a Phase 1b dose-expansion cohort evaluating E7386 (a CBP/β-catenin interaction inhibitor) in combination with lenvatinib in patients with advanced endometrial carcinoma with progression following prior anti-PD-(L)1 immunotherapy and platinum-based chemotherapy (NCT04008797; Presentation: #738P); as well as presentations for BB-1701...in previously-treated patients with HER2-positive or HER2-low unresectable or metastatic breast cancer (NCT06188559; Presentation: #437TiP) and non-small cell lung cancer patients with HER2 mutation/amplification (Presentation: #1296P; presented by Bliss Biopharmaceutical Co., Ltd), respectively."

Clinical data • Endometrial Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer

Preclinical studies of BB-1701, a HER2-targeting eribulin-containing ADC with potent bystander effect and ICD activity. (PubMed, Antib Ther) - P1 | "The preclinical data support the test of BB-1701 in patients with various HER2-expressing cancers, including those resistant to other HER2-targeting ADCs. A phase I clinical trial of BB-1701 (NCT04257110) in patients is currently underway."

Journal • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Liposarcoma • Oncology • Sarcoma • Solid Tumor • HER-2

Updated safety and antitumor activity of BB-1701 from study 101 in the multiple dose level cohort of patients with locally advanced/metastatic HER2-low expressing breast cancer. (ASCO 2024) - P1 | "Background: BB-1701 is an antibody-drug conjugate (ADC) consisting of a humanized anti-HER2 antibody and eribulin. BB-1701 shows promising antitumor activity and a manageable safety profile in HER2 low-expressing breast cancer, including patients who received prior anti-HER2 ADCs."

Clinical • Metastases • Anemia • Breast Cancer • Dyslipidemia • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hypertriglyceridemia • Musculoskeletal Diseases • Oncology • Pain • Solid Tumor • CTSB • HER-2

EISAI SHOWCASES ONCOLOGY PORTFOLIO AND PIPELINE AT ASCO 2024 (Eisai Press Release) - "Additional pipeline research to be presented in poster sessions include an overview of a Phase 2 study of BB-1701, an antibody drug conjugate targeting HER2, in previously treated patients with HER2-positive or HER2-low unresectable or metastatic breast cancer (NCT06188559; Abstract #TPS1122), findings from a Phase 1b trial of tasurgratinib (development code: E7090) with or without endocrine therapies for patients with ER-positive, HER2−negative recurrent/metastatic breast cancer after receiving a CDK4/6 inhibitor (NCT04572295; Abstract #3103), as well as the dose-expansion part of a Phase 1b global study of E7386 in combination with lenvatinib in patients with hepatocellular carcinoma and other solid tumors including endometrial cancer (NCT04008797; Abstract #TPS3169)."

P1 data • Trial status • Endometrial Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer

A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Eisai Inc. | Not yet recruiting ➔ Recruiting

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

Angle PLC - Contract announcement with Eisai Inc. (ACCESSWIRE) - "ANGLE plc...is delighted to announce that it has signed a contract with the global pharmaceutical company, Eisai Inc...Under the agreement, in a pilot study worth US $250,000 to ANGLE, ANGLE will provide CTC analysis with its Portrait HER2 assay to assess breast cancer patients' HER2 (human epidermal growth factor receptor 2) status in a Phase II study of the HER2 targeting antibody-drug conjugate (ADC) BB-1701. Success in the pilot study offers the potential for multiple large scale follow-up studies....ANGLE's Portrait HER2 assay enables quantitative assessment of both HER2 protein expression (via IF) and HER2/neu gene amplification (via FISH) to identify patients who could benefit from anti-HER2 ADC treatment."

Diagnostic • Licensing / partnership • Breast Cancer • Oncology • Solid Tumor • HER-2

A Study of BB-1701 in Previously Treated Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive or HER2-low Unresectable or Metastatic Breast Cancer (clinicaltrials.gov) - P2 | N=135 | Not yet recruiting | Sponsor: Eisai Inc.

Metastases • New P2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

Report on Cohort Expansion of Phase I Study to Investigate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of BB-1701 in Patients with Locally Advanced/Metastatic HER2 Low Breast Cancer (SABCS 2023) - "Background: BB-1701 is an antibody-drug conjugate (ADC) consisting of a humanized IgG1κ monoclonal anti-HER2 antibody with the same sequence as trastuzumab and eribulin linked together by a cathepsin-cleavable valine-citrulline linker...One patient who achieved PR was previously progressed on sacituzumab govitecan... BB-1701 has demonstrated promising preliminary antitumor activity in HER2 low breast cancer including patients who received prior anti-HER2 ADCs, and a manageable safety profile."

Clinical • Metastases • P1 data • PK/PD data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CTSB • HER-2