OBI-888 / OBI Pharma - LARVOL DELTA

Phase I-II study of OBI-888, a humanized monoclonal IgG1 antibody against the tumor-associated carbohydrate antigen Globo H, in patients with advanced solid tumors. (PubMed, Cancer Chemother Pharmacol) - "OBI-888 was well tolerated. Prolonged SD was noted in three patients. ADCC was induced after each OBI-888 treatment."

Journal • Metastases • P1/2 data • Oncology • Solid Tumor

Globo H-targeted CAR T cell cancer immunotherapy (AACR 2023) - "Clinical studies with the Globo H vaccines (OBI-822 and OBI-833) and the humanized anti-Globo H antibody (OBI-888) demonstrating an excellent safety profile...As a result, development of CAR T targeting GH may offer a novel anticancer therapeutic agent.Aim: The aim of this study was to develop a CAR T cell therapy targeted against Globo H (obi-R007) using lentivirus-mediated genetic engineering with a proprietary Globo H-specific antibody... In conclusion, our in vitro and in vivo pharmacology and preliminary toxicology studies support clinical development of Globo H CAR T immunotherapy for patients with cancer."

CAR T-Cell Therapy • IO biomarker • Breast Cancer • Colon Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD69 • GZMB • IFNG • IL2 • IL2RA • LAG3 • PD-1

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[VIRTUAL] The prevalence of Globo H in different tumor types: Breast, pancreatic, lung, gastric, colorectal, liver, and esophageal cancers (AACR-II 2020) - P1/2 | "Using an H-score of 100 as a cutoff [approved in the Investigational Device Exemption (IDE) application as a pre-screening criterion of GH monoclonal antibody in the Phase 2 clinical trial OBI-888-001 (NCT03573544)], the GH prevalence of the pancreatic, esophageal, gastric, breast, lung, colorectal, and liver cancers are 50%, 17.2%, 24.7%, 13%, 10.4%, 16%, and 0%, respectively... Overexpression of GH in human pancreatic, gastric, lung, colorectal, esophageal, and breast tumors renders GH a potential therapeutic target for these cancers. Furthermore, the presence of GH-positive immune cells in the intra- or peri-tumor region lends support to the proposed mechanism of cancerous cells shedding GH-ceramide to suppress normal immune functions. The heterogeneous expression of GH among different molecular subtypes may provide a biomarker in the selection of patients for GH-directed therapies."

Breast Cancer • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Anti-tumor efficacy and potential mechanism of action of a novel therapeutic humanized anti-Globo H antibody, OBI-888 (AACR 2019) - P1; "Study demonstrated OBI-888’s ability to trigger ADCC, ADCP, and CDC, mechanisms by which antibody induces tumor lysis. ADCC was further supported by OBI-888’s binding affinity to multiple FcγRs, including a low affinity genotype which can potentially benefit those patients who belong to low affinity genotype. GH-cer showed immunosuppresive effect, as manifested by GH staining on the immune cells."

Clinical

First-in-Human Study of OBI-999, a Globo H-Targeting Antibody-Drug Conjugate, in Patients With Advanced Solid Tumors. (PubMed, JCO Precis Oncol) - P1/2 | "The recommended phase II dose was determined to be 1.2 mg/kg once every 3 weeks. A phase II cohort-expansion study is now enrolling patients with pancreatic, colorectal, and other cancers expressing high levels of Globo H."

Journal • Metastases • P1 data • Adenoid Cystic Carcinoma • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Lung Cancer • Neutropenia • Oncology • Oropharyngeal Cancer • Pancreatic Cancer • Solid Tumor

This Study is to Evaluate Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. (clinicaltrials.gov) - P1/2 | N=54 | Terminated | Sponsor: OBI Pharma, Inc | N=168 ➔ 54 | Trial completion date: Dec 2022 ➔ Apr 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2022 ➔ Apr 2022; OBI-888 no longer fulfills our goal of developing cost-effective therapies for cancer patients

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

OBI Pharma Announces Discontinuation of the Phase 1/2 Study of its Antibody- OBI 888 to focus on other priority Cancer programs (GlobeNewswire) - "OBI Pharma...announced discontinuation of the Phase 1/2 Study for OBI 888, a Globo H antibody, upon completion of enrollment....'Due to the higher antibody amount required for the OBI-888 treatment...and an unexpected low drug yield at the large manufacturing scale, OBI-888 no longer fulfills our goal of developing cost-effective therapies for cancer patients. We have therefore decided to discontinue OBI-888 development and focus on our novel cancer pipeline under Phase 3...and Phase 2...clinical development. The OBI-888 clinical study report is estimated to be finalized in Q4, 2022 and presented at a future medical conference."

Discontinued • P1/2 data • Oncology • Solid Tumor

This Study is to Evaluate Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. (clinicaltrials.gov) - P1/2; N=168; Active, not recruiting; Sponsor: OBI Pharma, Inc; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

This Study is to Evaluate Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. (clinicaltrials.gov) - P1/2; N=168; Recruiting; Sponsor: OBI Pharma, Inc; Trial completion date: Jun 2021 ➔ Dec 2022; Trial primary completion date: May 2021 ➔ Nov 2022

Clinical • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

OBI Pharma updates on clinical trial activities during COVID-19 pandemic (PRNewswire) - “…we will place a three-month pause to the Adagloxad Simolenin Phase 3 GLORIA Triple-Negative Breast Cancer (TNBC) study, enrollment to ongoing Phase 1/2 clinical trials and activations of new research sites…Other OBI products under Phase 1/2 clinical studies (OBI-888, OBI-999 and OBI-3424) have also been affected by the global restrictions at clinical sites due to the COVID-19 pandemic. These studies will be monitored for re-engagement on an ongoing basis.”

Clinical • Enrollment status • Trial status • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

This Study is to Evaluate Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. (clinicaltrials.gov) - P1/2; N=168; Recruiting; Sponsor: OBI Pharma, Inc; N=58 ➔ 168

Clinical • Enrollment change

This Study is to Evaluate Safe and Effective Treatment Dose of OBI-888 in Patients With Locally Advanced or Metastatic Solid Tumors. (clinicaltrials.gov) - P1/2; N=58; Recruiting; Sponsor: OBI Pharma, Inc; Phase classification: P1 ➔ P1/2

Clinical • Phase classification

Novel Globo H targeting antibody-drug conjugate with binding specificity and anti-tumor efficacy in multiple cancer types (AACR 2019) - "...OBI-999 is an antibody-drug conjugate (ADC) which consists of a Globo H-specific monoclonal antibody OBI-888, conjugated with monomethyl auristatin E (MMAE), a synthetic antineoplastic agent...In vitro serum stability studies revealed that OBI-999 has comparable stabilities to Adcetris® in mouse, rat, monkey, and human sera... The preclinical studies of OBI-999 demonstrated its targeting specificity and anti-tumor efficacy in multiple Globo H positive cancer models. OBI-999 also demonstrated a longer retention at tumor site. The preclinical results provided the fundamental basis for OBI-999’s clinical application as targeted cytotoxicity therapy for solid tumors."

Clinical • IO Biomarker

Specificity, biodistribution, tumor targeting, and pharmacokinetics of a novel humanized anti-Globo H antibody, OBI-888, for cancer immunotherapy (AACR 2019) - "The present study identified the epitope of OBI-888 and demonstrated its binding specificity. The observed biodistribution and microSPECT results demonstrated OBI-888’s specific targeting to GH positive tumor cells. Pharmacokinetic profiles showed acceptable half-lives in mice."

PK/PD data

OBI Pharma announces poster presentations at AACR 2019 for novel Globo H immuno-oncology therapeutics: OBI-888 and OBI-999 (PRNewswire) - "OBI Pharma, Inc...announced that data highlighting OBI-888 (Globo H mAb) and OBI-999 (Globo H ADC) mechanism of action, anti-tumor efficacy and pharmacokinetics profile in multiple cancer types, will be presented at the American Association of Cancer Research (AACR) Annual Meeting....For OBI-999, preliminary pharmacological studies in established animal tumor models showed potent and long lasting anti-tumor activity in multiple cancer types, including breast, pancreatic, lung and gastric cancer. A US FDA IND submission is planned for 2019."

IND • Preclinical