ifabotuzumab (KB004) / Humanigen, Olivia Newton-John Cancer Research Institute - LARVOL DELTA

Pythium and Globisporangium species associated with cucumber rhizosphere causing damping-off and their effects on cucumber seed decay in Oman. (PubMed, Arch Microbiol) - "Pythium aphanidermatum, P. myriotylum, Globisporangium spinosum, Globisporangium sp.1 (isolates Kb003/PySyCu-1 and Kb004/PySyCu-2), and Globisporangium sp.2 (isolate Ib002R) were identified. This study showed that P. aphanidermatum is the most prevalent species in greenhouses in Oman and exhibited a moderate level of genetic diversity. Most of the isolates exhibited differences in tolerance to hymexazol but showed no resistance."

Journal

Targeting the tumour microenvironment in pancreatic cancer (EACR 2024) - "shRNA knockdown of TME-expressed EphA3 was achieved using KPC (K-Ras/p53 mutant) tumour allografts in transgenic mice with doxycycline-induced expression of EphA3 shRNA {Vail, 2023 #5666}. An anti-EphA3 antibody-drug conjugate (ADC) was developed using the EphA3 antibody ifabotuzumab coupled with the DNA-binding toxin pyrrolobenzodiazepine (PBD).Results and Discussions Single-cell RNA sequencing data from K-Ras mutant mouse PDAC showed EphA3 expression in the TME, particularly in myCAFs...Lastly, we have also developed a novel anti-EphA3 ADC which caused significant inhibition of PDAC growth in mice.Conclusion The EphA3 receptor is expressed in CAF subtypes within the pancreatic TME and supports tumour growth. Use of our anti-EphA3 ADC has potential as a novel TME-targeted therapeutic approach."

Tumor microenvironment • Fibrosis • Gastrointestinal Cancer • Hepatology • Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CAFs • EPHA3 • KRAS • TP53

Preliminary findings of a phase I safety and bioimaging trial of KB004 (ifabotuzumab) in patients with glioblastoma. (SNO 2019) - " To date, 7 of 12 pts have enrolled (6 at 3.5 mg/kg ,1 at 5.25 mg/kg; Mean age: 55 years (±12.6), 4 are male).  Treatment emergent AEs included infusion reactions, seizures, cerebral oedema, rash, pruritis, headaches, eye disorder. Most were considered related to study drug, seizures and infusion reactions were readily managed with increased premedications after the first occurrence. Best response in cohort 1 is SD for 23 weeks."

Clinical • P1 data • EPHA3

Humanigen Announces Participation and Presentation at Jefferies London Healthcare Conference (Yahoo Finance) - "Humanigen, Inc...announced that Cameron Durrant, MD, MBA, Chairman & CEO, will give a corporate presentation at 11:25am EST (4:25pm local time) at the Jefferies London Healthcare Conference taking place on November 17, 2022. Dr. Durrant will provide an update on the clinical development of lenzilumab, Ifabotuzumab and HGEN005." "

Clinical data • Oncology

Humanigen Reports Second Quarter 2022 Financial Results (Businesswire) - "'We have increased the number of sites for the PREACH-M study in Australia of lenzilumab in chronic myelomonocytic leukemia (‘CMML’), a rare blood cancer, and have interest from top oncology centers in the United States....In addition, we are currently assessing requests for investigator-initiated trials (‘IIT’s’) of lenzilumab in combination with CAR-T therapies and plan to continue the development of ifabotuzumab (‘iFab’), an EpAh-3 targeted monoclonal antibody currently in Phase 1 development, as part of an antibody drug conjugate (‘ADC’), for certain solid tumors in Australia'."

Trial status • Hematological Malignancies • Oncology

A Trial of KB004 in Patients With Glioblastoma (clinicaltrials.gov) - P1; N=12; Completed; Sponsor: Olivia Newton-John Cancer Research Institute; Active, not recruiting ➔ Completed

Clinical • Trial completion • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • EPHA3 • MRI

Humanigen announces preparation of Phase 1b study of ifabotuzumab in solid tumors following presentation of Phase 1 study results at EANM‘21 (Businesswire) - "Humanigen, Inc...announced its research partners will present Phase 1 results from a study of ifabotuzumab in glioblastoma multiforme (GBM) at the Annual Congress of the European Association of Nuclear Medicine (EANM’21) and plan to initiate a follow-on Phase 1b study in non-CNS solid tumors in early 2022....The Olivia Newton-John Cancer Research Institute plans to conduct a Phase 1b dose-escalation and imaging study in non-CNS solid tumors that is scheduled to begin in early 2022."

P1 data • Glioblastoma • Oncology

A Trial of KB004 in Patients With Glioblastoma (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: Olivia Newton-John Cancer Research Institute; Trial completion date: Apr 2021 ➔ Sep 2021

Clinical • Trial completion date • Brain Cancer • Glioblastoma • Neutropenia • Oncology • Solid Tumor • EPHA3 • MRI

[VIRTUAL] Phase I safety and bioimaging trial of ifabotuzumab in patients with glioblastoma. (AACR 2021) - "Ifabotuzumab demonstrates highly sensitive, specific and reproducible targeting of the tumor and tumor microenvironment in all patients in this study. The imaging changes suggest direct modulation of the tumor vasculature. Additional studies are planned to evaluate ifabotuzumab as part of an antibody-drug conjugate in various solid tumor types."

Clinical • P1 data • Glioblastoma • Hematological Malignancies • Oncology • Solid Tumor • EPHA3 • MRI

Antibody-mediated depletion of CCR10+ EphA3+ cells ameliorates fibrosis in IPF. (PubMed, JCI Insight) - "Ifabotuzumab-targeted killing of EphA3+ cells significantly reduced the numbers of CCR10+ cells and ameliorated pulmonary fibrosis in humanized NSG mice. Thus, human CCR10+ cells promote pulmonary fibrosis and EphA3 mAb-directed elimination of these cells inhibits lung fibrosis."

Journal • Fibrosis • Idiopathic Pulmonary Fibrosis • Immunology • Pulmonary Disease • Respiratory Diseases • CCR10 • EPHA3

Humanigen Announces Positive Results From Phase 1 Study of Ifabotuzumab in Glioblastoma Multiforme (Businesswire) - P1, N=12; NCT03374943; “Humanigen, Inc…announced positive results from the Phase 1 safety and bioimaging trial of its second Humaneered® antibody, ifabotuzumab, in patients with glioblastoma multiforme (GBM). In the study, ifabotuzumab demonstrated highly sensitive, specific, and reproducible targeting of the tumor and tumor microenvironment in all patients. The results will be presented as a poster at the AACR Annual Meeting 2021, held virtually from April 10-15, 2021, and remain available until June 21, 2021…The study showed that, at both doses, ifabotuzumab demonstrated highly sensitive, specific, and reproducible targeting of the tumor and tumor microenvironment in all patients. There were no dose-limiting toxicities observed and all adverse events were readily manageable.”

P1 data • Glioblastoma • Oncology

Humanigen Reports Fourth Quarter and Year-End 2020 Financial Results and Provides Corporate Update (Businesswire) - "2021 Objectives Include: Report results on the ongoing Phase 1b/2 ZUMA-19 CAR-T clinical trials with Kite (a Gilead company) and the completed Phase 1 study with ifabotuzumab."

P1/2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Humanigen Announces Completion of Enrollment in Phase 1 Study of Ifabotuzumab in Glioblastoma Multiforme (Businesswire) - “Humanigen, Inc…announced completing enrollment in its Phase 1 bioimaging study of ifabotuzumab in patients with recurrent glioblastoma multiforme (GBM). Ifabotuzumab, or ifab, is the Company’s proprietary anti-EphA3 monoclonal antibody. This trial is supported by funding from the Cure Brain Cancer Foundation. Results from the study, being conducted at the Olivia Newton-John Cancer Research Institute in Heidelberg, Victoria, Australia, are expected in the first half of 2021.”

Enrollment closed • P1 data • Glioblastoma • Oncology

A Trial of KB004 in Patients With Glioblastoma (clinicaltrials.gov) - P1; N=12; Active, not recruiting; Sponsor: Olivia Newton-John Cancer Research Institute; Recruiting ➔ Active, not recruiting; Trial primary completion date: Oct 2020 ➔ Mar 2021

Clinical • Enrollment closed • Trial primary completion date • Brain Cancer • Glioblastoma • Neutropenia • Oncology • Solid Tumor

Humanigen Australia Proprietary Limited Established to Facilitate Asia-Pacific Growth Plans (Businesswire) - "This Phase 1 trial has enrolled 11 of the 12 patients targeted for full enrollment. Results are expected to be available in the first half of 2021."

New P1 trial • Brain Cancer • Glioblastoma • Oncology

EphA3-Expressing Lung Cells Contribute to Fibrosis in IPF (ATS 2019) - "...Nintedanib is a multi-tyrosine kinase inhibitor, which is now used clinically but patients on this medication still exhibit the loss of lung function indicating that other mechanisms might not be impacted by this therapeutic...Finally, targeting EphA3 expressing cells using an ADCC-inducing afucosylated anti-EphA3 antibody (i.e. KB004) ameliorated the fibrotic response at day 63 in NSG mice humanized with IPF lung cells compared with humanized NSG treated with a control IgG (KB00243) (See adjacent Figure)...Finally, targeting these cells using an ADCC-inducing afucosylated anti-EphA3 antibody ameliorated lung remodeling in NSG mice humanized with IPF explant cells. We conclude that EphA3 represents an attractive therapeutic target in IPF.Funding Sources: Cedars-Sinai Medical Center, NIH (HL123899)."

Preliminary findings of a Phase I safety and bioimaging trial of KB004 (ifabotuzumab) in patients with glioblastoma (AACR 2019) - "89Zr-Ifabotuzumab demonstrates sensitive, specific and reproducible targeting of the tumor microenvironment in GBM patients. The imaging changes suggest modulation of the tumor vasculature. Enrolment is on-going."

Clinical • P1 data

Humanigen Announces Preliminary Results From Ifabotuzumab Phase I Study Accepted for Presentation at the American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire, Humanigen, Inc) - P1, N=12; "Study Demonstrates that Dosing with Ifabotuzumab Results in Rapid, Specific and Reproducible Targeting of the Tumor Microenvironment in Patients with Glioblastoma Multiforme (GBM) . Imaging Changes Suggest Modulation of the Tumor Vasculature by Ifabotuzumab without Normal Tissue Uptake."

P1 data