ibentatug (ZB131) / ZielBio - LARVOL DELTA

Plectin as a novel therapeutic target for pancreatic cancer (AACR 2025) - P1/2 | "Recently, a phase 1 clinical trial using an anti-CSP antibody, ZB131 (NCT05074472) in CSP positive cancer subtypes showed ZB131 as a viable and safe drug candidate for treatment...Additionally, treatment with anti-CSP antibody led to a decrease in classic signaling cascades associated with cancer progression such as SRC, PRAS40, STAT3, AKT, and ERK1/2. The cumulative work from this research highlights the role of CSP in PDAC and suggests a desperate need for an anti-CSP therapeutic for patients."

Biliary Cancer • Cholangiocarcinoma • Oncology • Ovarian Cancer • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • AKT1S1 • PLEC • STAT3

A Phase 1/2, First-in-Human, Open Label, Dose Escalation Study Of A CSP Targeting Functional Antibody in Solid Tumors (clinicaltrials.gov) - P1/2 | N=35 | Completed | Sponsor: ZielBio, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Mar 2024 ➔ Sep 2023 | Trial primary completion date: Jan 2024 ➔ Aug 2023

Trial completion • Trial completion date • Trial primary completion date • Biliary Cancer • Hepatology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase 1/2, First-in-Human, Open Label, Dose Escalation Study Of A CSP Targeting Functional Antibody in Solid Tumors (clinicaltrials.gov) - P1/2 | N=37 | Active, not recruiting | Sponsor: ZielBio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Biliary Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A phase 1/2, first-in-human trial of ZB131, a novel antibody targeting cancer-specific plectin (CSP) in advanced solid tumors. (ASCO 2023) - "Interim data from dose-escalation of this first-in-class, anti CSP antibody, demonstrates good tolerability with encouraging signs of activity and target engagement in heavily pretreated pts. Results support further clinical evaluation of ZB131 in dose-expansion cohorts including OC and including combination therapy with gemcitabine. Clinical trial information: NCT 05074472."

Metastases • P1/2 data • Anemia • Biliary Cancer • Cholangiocarcinoma • Fatigue • Gastrointestinal Cancer • Hematological Disorders • Neutropenia • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • MUC16 • PLEC

ZielBio to Present Interim Findings from its Phase 1/2, First-in-Human Trial of ZB131 at 2023 ASCO Annual Meeting (PRNewswire) - P1/2 | N=37 | NCT05074472 | Sponsor: ZielBio, Inc. | "ZielBio, Inc...will present the first set of clinical data from its lead asset, ZB131, directed against cancer-specific plectin (CSP), during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. In an interim analysis (n=32) of the Phase 1/2 trial, ZB131 demonstrated a favorable safety and tolerability profile, evidence of clinical activity and dose-proportional pharmacokinetics."

P1/2 data • Oncology • Solid Tumor

ZB131 antibody-drug conjugates induce potent antitumor activity (AACR 2023) - P1, P1/2 | "Furthermore, anti-huIgG staining revealed selective target engagement by ZB131-ADC. Taken together, these data show that ZB131-ADCs demonstrate potent antitumor activity and support their evaluation in a Phase 1 clinical trial."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • PLEC

"#ZielBio to Present New Research on the Utility of #CancerSpecificPlectin (CSP) and #ZB131 in #AntibodyDrugConjugates at #AACR23 https://t.co/Q5SAwIgJ14" (@1stOncology)

Oncology

ZielBio to Present New Research on the Utility of Cancer-Specific Plectin (CSP) and ZB131 in Antibody-Drug Conjugates at AACR Annual Meeting 2023 (PRNewswire) - "Research presented at AACR will focus on CSP as a target for ADCs, demonstrating its abundance on the surface of cancer cells (and not healthy tissue), its bioavailability in humans, and its application across multiple cancer indications. ZB131 demonstrates favorable pharmacokinetics, is rapidly internalized by CSP-expressing tumor cells in mouse models, and can be conjugated to multiple cytotoxic payloads."

Preclinical • Oncology • Solid Tumor

ZielBio Appoints Alan Bash CEO as Company Advances Oncology Therapeutics (PRNewswire) - "The appointment of Mr. Bash comes as ZielBio reaches the completion of enrollment in the Phase 1, dose escalation, open-label study of lead asset ZB131 (proposed international nonproprietary name Ibentatug), a cancer specific plectin (CSP)-targeting functional antibody, in tumors likely to express CSP. The company plans to open Phase 2 expansion cohorts with ZB131 as monotherapy and in combination with a standard of care therapeutic in the first quarter of 2023."

Enrollment status • Trial status • Oncology

ZielBio Receives Orphan Drug Designation for ZB131 for the Treatment of Pancreatic Cancer (PRNewswire) - "ZielBio, Inc....announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to its lead program, ZB131, for the treatment of treatment of pancreatic cancer, a rare solid-tumor cancer originating from the pancreas....A Phase 1/2 trial is underway to study the safety, tolerability, and efficacy of ZB131 in patients with solid tumors, including cholangiocarcinoma, pancreatic, and ovarian cancers."

Orphan drug • Trial status • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor

ZielBio Receives Orphan Drug Designation for ZB131 for the Treatment of Cholangiocarcinoma (PRNewswire) - "ZielBio, Inc....today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to its lead program, ZB131, for the treatment of cholangiocarcinoma, a rare solid-tumor cancer originating from the bile duct system. ZB131 is a monoclonal antibody with a high affinity and specificity for cancer-specific plectin (CSP), a cell surface protein identified in a wide range of cancers that correlates with poor prognosis and aggressive tumors."

Orphan drug • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

First in class drug ZB131 shows efficacy in cholangiocarcinoma models (AACR 2022) - "Previous data from our group and others suggesting that CSP plays a role in chemoresistance led us to evaluate the efficacy of ZB131 in combination with gemcitabine. In summary, ZB131 is an exciting new avenue for the treatment of CCA and other CSP-positive cancers with an excellent safety profile and strong antitumor activity in vitro and in murine models. Phase I clinical trials of ZB131 have been initiated."

Clinical • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • FGFR2 • IDH1 • PLEC

ZielBio to Present New Data Demonstrating Preclinical Efficacy of ZB131 in Cholangiocarcinoma at AACR Annual Meeting 2022 (PRNewswire) - "ZielBio, Inc...will present new, preclinical data on the efficacy of its ZB131 drug in cholangiocarcinoma (CCA) models at the American Association for Cancer Research (AACR) Annual Meeting 2022....ZB131 significantly suppressed tumor growth in the majority of mice, and caused complete regression in 17% of mice. In another group of CCA-xenografted mice, ZB131 was administered in combination with the chemotherapy drug gemcitabine (100 mg/kg). In this group, ZB131 showed an increased tumor response (91% suppression) when compared to gemcitabine alone (74% suppression)."

Preclinical • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology

ZielBio Announces First Patient Dosed in Phase 1/2 Clinical Trial of ZB131, Its Novel Monoclonal Antibody Targeting Cancer Specific Plectin (PRNewswire) - "ZielBio...announced the first patient dosed in its Phase 1/2 clinical trial. The study will evaluate ZB131 in patients with solid tumors who are either non-responsive to or ineligible for the standard of care. ZB131 is a monoclonal antibody with a high affinity and specificity for cancer specific plectin (CSP), a cell surface protein identified in a wide range of cancers that correlates with poor prognosis and aggressive tumors."

Trial status • Oncology • Solid Tumor

A Phase 1/2, First-in-Human, Open Label, Dose Escalation Study Of A CSP Targeting Functional Antibody in Solid Tumors (clinicaltrials.gov) - P1/2 | N=37 | Recruiting | Sponsor: ZielBio, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

A Phase 1/2, First-in-Human, Open Label, Dose Escalation Study Of A CSP Targeting Functional Antibody in Solid Tumors (clinicaltrials.gov) - P1/2; N=37; Not yet recruiting; Sponsor: ZielBio, Inc.

Clinical • New P1/2 trial • Biliary Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

[VIRTUAL] A novel monoclonal antibody targeting cell-surface plectin has potent antitumor activity in ovarian cancer models (AACR 2021) - "Similar in-vivo and in-vitro techniques were used to characterize ZB131’s effect in combination with cisplatin. ZB131 demonstrates high affinity (0.4±0.1nM) and specificity for both murine and human CSP. CSP is a novel highly abundant therapeutic target exclusively localized to the cell surface of ovarian, colorectal, lung, and pancreatic cancers which collectively account for more than half of all estimated cancer deaths. Our findings illustrate that CSP-targeting with ZB131 induces cytotoxicity by activating stress pathways and dampening proliferation and survival pathways. This study serves as the basis for informing a novel treatment strategy for CSP-positive tumors."

Preclinical • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Pancreatic Cancer • Solid Tumor • AKT1S1 • AMPK • PLEC