HMBD-001 / Hummingbird Biosci - LARVOL DELTA

Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation (clinicaltrials.gov) - P1 | N=68 | Active, not recruiting | Sponsor: Hummingbird Bioscience | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • EGF • ERBB3 • NRG1

The Christie sees promise in HMBD-001 for bladder cancer (Clinical Trials Arena) - P1/2a | N=81 | NCT05057013 | "Sponsored by Cancer Research UK, the Phase I/II trial (NCT05057013) is looking to establish the best dose of HMBD-001, to be administered either alone or in combination with other anti-cancer agents....The Christie has reported that patients showed promising results in dose escalation part A of the trial...weekly, intravenously administered HMBD-001 has seen his cancer reduce by over 60% in his liver. As part of the investigational treatment protocol, the pelvis area was treated with radiotherapy and the tumour on the lymph node was reduced by three-quarters its original size, making it barely visible on scans."

P1/2 data • Bladder Cancer

CRUKD/22/002: A Phase I/IIa Trial of HMBD-001 in Advanced HER3 Positive Solid Tumours (clinicaltrials.gov) - P1/2 | N=81 | Recruiting | Sponsor: Cancer Research UK | N=135 ➔ 81

Enrollment change • Metastases • Bladder Cancer • Breast Cancer • Castration-Resistant Prostate Cancer • Cervical Cancer • Colorectal Cancer • Endometrial Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hepatocellular Cancer • Hepatology • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • ERBB3 • NRG1

Study of an Anti-HER3 Antibody, HMBD-001, with Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers, and HMBD-001 + Cetuximab in Advance Squamous Cell Cancers (clinicaltrials.gov) - P1/2 | N=98 | Recruiting | Sponsor: Hummingbird Bioscience | N=62 ➔ 98

Enrollment change • Cervical Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Squamous Cell Skin Cancer

Trial in Progress: A Phase Ib Study of HMBD-001, An Anti-HER3 Antibody, in Advanced Squamous Non-Small Cell Lung Cancer (IASLC-WCLC 2024) - "The study evaluates two treatment regimens (Arm A: HMBD-001 + docetaxel; Arm B: HMBD-001 + cetuximab + docetaxel) in patients with advanced or metastatic sqNSCLC following progression on platinum-based chemotherapy and ICIs. Exploratory analysis of genomic alterations in the MAPK and PI3K pathways will be performed and correlated with ORR. Enrollment of patients into the first stage of the study is currently ongoing."

IO biomarker • Metastases • P1 data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • ERBB3 • HER-2

A HER3 antibody that uniquely blocks the HER3 heterodimerization interface effectively inhibits tumor growth in pre-clinical models with potentially oncogenic HER3 mutations (AACR 2024) - P1 | "In multiple cell- and patient-derived xenograft models with HER3 mutations HMBD-001 response achieved >80% tumor growth inhibition. Based on this encouraging preclinical data, a Phase Ib clinical trial (NCT05919537) has been initiated, evaluating HMBD-001 in patients with aberrant HER3 signaling, including HER3 mutations."

Preclinical • Oncology • EGFR • HER-2 • NRG1

Hummingbird Bioscience to Present Two Posters on Anti-HER3 and Anti-VISTA Antibody Therapeutics at American Association for Cancer Research (AACR) Meeting 2024 (PRNewswire) - "Hummingbird Bioscience...announced two upcoming poster presentations at the American Association for Cancer Research (AACR) Meeting 2024....Presentations will highlight the broad potential treatment opportunities for its clinical-stage targeted therapeutics HMBD-001 (anti-HER3 mAb) and HMBD-002 (anti-VISTA mAb) with further demonstrations of their pre-clinical efficacy in additional indications and deeper studies of their underlying therapeutic mechanisms."

Preclinical • Oncology

Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers (clinicaltrials.gov) - P1/2 | N=62 | Recruiting | Sponsor: Hummingbird Bioscience

Combination therapy • Metastases • Trial initiation date • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A phase Ib study of HMBD-001, a monoclonal antibody targeting HER3, with or without chemotherapy in patients with genetic aberrations in HER3 signaling (ESMO Asia 2023) - P1 | "The study evaluates HMBD-001 in combination with standard of care chemotherapy in two cohorts: NRG1 fusions in PDAC (HMBD-001 + nab-paclitaxel + gemcitabine) and in NSCLC (HMBD-001 + docetaxel) and HMBD-001 monotherapy in two other cohorts: NRG1 fusions in other solid tumors and selected HER3 ECD mutations across solid tumors. The primary objectives are to determine the safety and tolerability of all combination regimens and to assess the preliminary anti-tumor activity in terms of objective response rate (ORR) by RECIST v1.1 for all regimens. Secondary endpoints include duration of response (DOR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and pharmacokinetic (PK) and immunogenicity profile analysis."

Clinical • P1 data • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ERBB3 • HER-2 • NRG1

Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers (clinicaltrials.gov) - P1/2 | N=62 | Recruiting | Sponsor: Hummingbird Bioscience | Phase classification: P1b ➔ P1/2

Phase classification • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation (clinicaltrials.gov) - P1 | N=68 | Recruiting | Sponsor: Hummingbird Bioscience | Phase classification: P1b ➔ P1

Metastases • Phase classification • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • EGF • ERBB3 • NRG1

Pharmacokinetics of HMBD-001, a human monoclonal antibody targeting HER3, a CRUK first-in-human phase I trial in patients with advanced solid tumours (ESMO 2023) - P1/2 | "Table: 688P Pharmacokinetics of HMBD-001 on day 1 of dosing Conclusions The pharmacokinetic data generated to date are consistent with dose-dependent increases in drug exposure for HMBD-001. A T1/2 of approximately 12 days is predicted."

Clinical • Metastases • P1 data • PK/PD data • Oncology • Solid Tumor • EGFR • ERBB3 • HER-2

A CRUK phase I/IIA, first in human dose-escalation and expansion trial of HMBD-001 (an anti-HER3 antibody) in patients with advanced HER3 positive solid tumours (ESMO 2023) - P1/2 | "HMBD-001 will next be evaluated in Part B in biomarker selected mCRPC with Enzalutamide. Trials of HMBD-001 in squamous NSCLC and NRG1 fusions are also planned for Q3/4 2023."

Clinical • Metastases • P1/2 data • Genito-urinary Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • ERBB3 • HER-2 • NRG1

Hummingbird Bioscience Announces Positive Phase I Clinical Data for HMBD-001 Monotherapy Trial at the European Society for Medical Oncology Congress 2023 (PRNewswire) - P1/2 | N=135 | NCT05057013 | "Hummingbird Bioscience...announced presentation of positive clinical data for the dose escalation part of the HMBD-001 Phase I/IIa trial (NCT05057013) at the European Society for Medical Oncology Congress 2023 (ESMO 2023). The trial is evaluating HMBD-001 as a monotherapy across various tumor types in the UK....The dose escalation trial cleared six monotherapy cohorts with no dose-limiting toxicities (DLTs) and there were no treatment discontinuations due to related adverse events. Of the enrolled patients, 21 were evaluable for efficacy. Disease control rate (DCR) was 43% (9/21), with one patient achieving partial response with a 51% tumor shrinkage after four cycles of HMBD-001 treatment. HMBD-001 as monotherapy had a maximal half-life of 12 days in this trial."

P1/2 data • Oncology • Solid Tumor

Combining Anti-HER3 Antibody, HMBD-001, with EGFR Inhibition and Chemotherapy may Improve Treatment Outcomes in SqNSCLC (IASLC-WCLC 2023) - "Potency of HMBD-001 to inhibit tumor growth as monotherapy or in combination with cetuximab and/or docetaxel was evaluated using murine CDX and PDX models. An analysis of copy number variations and expression of genes in Chr3q, Chr3p and Chr7p confirms that genes involved in HER3 signaling are frequently amplified and have higher expression in squamous compared to non-squamous NSCLC. Several genetic alterations in sqNSCLC lead to HER3 and EGFR pathway activation. HMBD-001, a potent anti-HER3 mAb, in combination with EGFR inhibition and chemotherapy, has the potential to greatly improve clinical outcomes following immune-chemotherapy. Hummingbird Bioscience plans to initiate Phase Ib clinical trials in biomarker selected populations of sqNSCLC in H2, 2023."

Clinical • IO biomarker • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • PIK3CA

Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers (clinicaltrials.gov) - P1b | N=62 | Recruiting | Sponsor: Hummingbird Bioscience | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Hummingbird Bioscience to Present Poster on HMBD-001 Combination Strategy for Squamous Non-Small Cell Lung Cancer at World Conference on Lung Cancer 2023 (PRNewswire) - "Hummingbird Bioscience...announced an upcoming poster presentation at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (9-12 September 2023, Singapore). The poster will highlight the scientific rationale for combining anti-HER3 antibody HMBD-001 with EGFR inhibition and chemotherapy to improve treatment outcomes in squamous non-small cell lung cancer (sqNSCLC)."

Clinical data • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With NRG1 Gene Fusion Advanced Solid Tumors (clinicaltrials.gov) - P1b | N=54 | Recruiting | Sponsor: Hummingbird Bioscience | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • EGF • NRG1

Hummingbird Bioscience Initiates HMBD-001 Phase IB Trials in Australia and Partners with Omico to Accelerate Clinical Development (PRNewswire-Asia) - "Hummingbird Bioscience...announced the initiation of two Phase IB clinical trials in Australia. The Hummingbird Bioscience-sponsored precision oncology trials will evaluate the activity of HMBD-001, a differentiated HER3-targeting antibody that uniquely inhibits HER3 oncogenic signaling, in patients with squamous non-small cell lung carcinoma (sqNSCLC), and patients with genetic aberrations in HER3 signaling....Hummingbird Bioscience has partnered with Omico to accelerate clinical development of HMBD-001, leveraging Omico's PrOSPeCT initiative and network in Australia to recruit patients with gene signatures most likely to benefit from HMBD-001."

Licensing / partnership • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With NRG1 Gene Fusion Advanced Solid Tumors (clinicaltrials.gov) - P1b | N=54 | Not yet recruiting | Sponsor: Hummingbird Bioscience

Metastases • New P1 trial • Gastrointestinal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • EGF • NRG1

Study of an Anti-HER3 Antibody, HMBD-001, With Docetaxel +/- Cetuximab in Advanced Squamous Non-small Cell Lung Cancers (clinicaltrials.gov) - P1b | N=62 | Not yet recruiting | Sponsor: Hummingbird Bioscience

Combination therapy • Metastases • New P1 trial • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Hummingbird Bioscience and Merck Enter Collaboration to Evaluate HMBD-001 In Squamous Non-Small Cell Lung Carcinoma (PRNewswire) - "Hummingbird Bioscience...announced it has entered into a clinical trial collaboration and supply agreement with Merck to evaluate HMBD-001 in combination with cetuximab in squamous non-small cell lung carcinoma (sqNSCLC). Under this collaboration, Hummingbird Bioscience will evaluate the safety, tolerability, and anti-tumor activity of its potentially best-in-class HER3-targeting antibody, HMBD-001, in combination with standard of care chemotherapy with or without Merck's cetuximab, anti-EGFR mAb, in patients with sqNSCLC in a Phase 1b clinical trial, to be initiated in the second half of 2023."

Licensing / partnership • New P1 trial • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Anti-HER3 antibody, HMBD-001, in combination with an EGFR inhibitor effectively inhibits tumor growth in biomarker-selected pre-clinical models of squamous cell carcinomas (AACR 2023) - P1/2 | "However, the combination of EGFR targeting antibody cetuximab with chemotherapy confers limited clinical benefit and even initially sensitive tumors often develop resistance. This study lays the foundation for testing HMBD-001 in combination with EGFR inhibitors in clinical settings. Better combination strategies of SoC and targeted therapeutics alongside a potent anti-HER3 mAb, in biomarker-selected patient populations, have the potential to meaningfully improve patient outcomes and prolong clinical benefit."

Combination therapy • Preclinical • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastrointestinal Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Non-melanoma Skin Cancer • Oncology • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Hummingbird Bioscience to Present Two Posters on HER3-Targeting Therapeutics at American Association for Cancer Research (AACR) Meeting 2023 (PRNewswire) - "Hummingbird Bioscience...announced two upcoming poster presentations at the American Association for Cancer Research (AACR) Meeting 2023....Presentations highlight the robust tumor growth inhibition in preclinical models for its HER3-targeting programs HMBD-001 (HER3 mAb) and HMBD-501 (HER3 ADC). HMBD-001 used as monotherapy or in combination with cetuximab effectively inhibits tumor growth in preclinical squamous cell carcinoma models. HMBD-501 shows superior preclinical efficacy and tolerability compared to other HER3 ADCs across a range of preclinical models, presenting a potentially best-in-class profile."

Preclinical • Oncology • Solid Tumor • Squamous Cell Carcinoma

Hummingbird Bioscience Exercises Its Option to License the Clinical Trial Results from Cancer Research UK to Support Further Development of HMBD-001 (PRNewswire) - "Hummingbird Bioscience...and Cancer Research Horizons...announced that Hummingbird Bioscience has exercised its option to license in the first-in-human (FIH) clinical trial results of HMBD-001, a differentiated and potentially best-in-class HER3-targeting antibody....Based on the FIH dose escalation data, Hummingbird Bioscience plans to initiate multiple studies in biomarker-selected populations during the second half of 2023. In parallel, CRUK will continue the ongoing Phase 1/2a study by completing the ongoing dose escalation portion, followed by a dose expansion study in metastatic castrate-resistant prostate cancer (in combination with anti-androgen therapy) later this year."

Licensing / partnership • New trial • Trial status • Bladder Cancer • Breast Cancer • Cervical Cancer • Endometrial Cancer • Gastric Cancer • Gastroesophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Gynecologic Cancers • Head and Neck Cancer • Hepatocellular Cancer • Liver Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Prostate Cancer • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer