OBI-999 / OBI Pharma, Abzena - LARVOL DELTA

OBI ANNOUNCES THE TERMINATION OF LICENSE AGREEMENT WITH ODEON FOR THE RIGHTS OF OBI-999 AND OBI-833 IN CHINA, HONG KONG AND MACAU (OBI Pharma Press Release) - "On 2022/2/22, OBI Pharma entered into a license agreement with Odeon Therapeutic...for the exclusive rights of OBI-999 and OBI-833 in China, Hong Kong and Macau, including the first right of negotiation for OBI-888 in China with a period of two years....Reason for termination: OBI has rebuilt its pipeline as a measure to the recent development of cancer therapy. Take OBI-888 as example, as the antibody drug yield rate was reduced during scale-up production, the manufacturing costs increase dramatically for commercial viability. Therefore, OBI resolved to discontinue its Phase II enrollment in 2022. Also, considering that OBI-999 has not shown its expected therapeutic potential for the enrolled patients in its clinical trial during past two years, OBI determined to stop further enrollment of patients in this Phase II trial and will focus existing resources on other ADC drugs in our pipeline."

Licensing / partnership • Trial termination • Oncology • Solid Tumor

Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=44 | Terminated | Sponsor: OBI Pharma, Inc | N=185 ➔ 44 | Trial completion date: Dec 2025 ➔ Oct 2023 | Recruiting ➔ Terminated | Trial primary completion date: Nov 2025 ➔ Oct 2023; Has not shown its expected therapeutic potential for the enrolled patients in this trial

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4

Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=185 | Recruiting | Sponsor: OBI Pharma, Inc | Trial completion date: Dec 2023 ➔ Dec 2025 | Trial primary completion date: Nov 2023 ➔ Nov 2025

Metastases • Trial completion date • Trial primary completion date • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4

HEXASACCHARIDE GLOBO-H AS A THERAPEUTIC TARGET FOR ANTIBODY-DRUG CONJUGATE OBI-999 IN TRIPLE- NEGATIVE BREAST CANCER (GBCC 2023) - P1/2 | "OBI-999 significantly reduces Globo-H-positive TNBC tumor growth by inducing apoptosis. Our data justify clinical trials targeting Globo-H for patients with advanced TNBC."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CASP3 • CASP7 • H2AX

OBI-999, an anti-Globo H antibody drug conjugate, exhibits synergistic anti-tumor effect in combination with pembrolizumab (AACR 2023) - P1/2 | "We demonstrated significant synergistic effects of OBI-999 and pembrolizumab in several animal models. These synergistic effects may be attributed to the ability of OBI-999 to induce ICD, as demonstrated by the release of DAMPs in vitro and tumor-specific immunity in vivo, suggesting that OBI-999 can create a tumor microenvironment that enhances the function of pembrolizumab. The results suggest that combination therapy with OBI-999 and immune checkpoint inhibitors is warranted in human clinical studies."

Combination therapy • IO biomarker • Breast Cancer • Colorectal Cancer • Lung Cancer • Oncology • Solid Tumor • CALR • CD4 • CD8 • CTSB • HMGB1 • PD-1 • PD-L1

OBI Pharma Announces Poster Presentations at AACR 2023 Annual Meeting for OBI-999 combination synergy with checkpoint inhibitor as well as Globo H-targeted CAR T-cell immunotherapy (GlobeNewswire) - "OBI Pharma...announced preclinical data demonstrating significant synergistic effects of OBI-999 and pembrolizumab (anti-PD1 mAb) in four different cancer models, as well as the potent antitumor effect of a chimeric antigen receptor T-cell (CAR T) immunotherapy targeting Globo H. These data will be presented at the American Association of Cancer Research (AACR) Annual Meeting from 14th-19th April, 2023 in Orlando, Florida (USA)....'Our scientific data suggest OBI-999 creates a tumor microenvironment that can significantly enhance the function of pembrolizumab. This potentiated anti-tumor effect was evident in four different xenograft models (breast, gastric, colorectal, and small cell lung cancer) that expressed Globo H and PD-1. These findings support the clinical study of combination therapeutic strategies that pair OBI-999 with anti PD-1/PD-L1 cancer therapeutics'."

Preclinical • Breast Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer

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

First-in-human study of OBI-999: A globo H-targeting antibody-drug conjugate in patients with advanced solid tumors. (ASCO 2022) - "We completed the dose-escalation portion of the study. OBI-999 was well tolerated. The recommended phase 2 dose was determined to be 1.2 mg/kg once every 3 weeks."

Clinical • P1 data • Adenoid Cystic Carcinoma • Anemia • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Nephrology • Neutropenia • Oncology • Oropharyngeal Cancer • Pancreatic Cancer • Renal Disease • Solid Tumor • CTSB

OBI Pharma Announces Poster Presentations at the 2022 ASCO Annual Meeting for Adagloxad Simolenin, OBI-999, OBI-3424, and Exhibition Booth (GlobeNewswire) - "OBI Pharma, Inc...announced that data highlighting ongoing clinical studies targeting Globo H and AKR1C3 in different tumor types will be presented at the American Society of Clinical Oncology (ASCO) meeting from June 3–7, 2022 in Chicago, IL (USA). These studies will be presented by the lead investigators of OBI Pharma’s first-in-class anti-Globo H cancer vaccine (Adagloxad Simolenin) and Antibody Drug Conjugate (OBI-999), and AKR1C3 targeting prodrug (OBI-3424)."

Clinical data • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

High Globo-H expression associated with poor survival of gastric cancer patients and enriched PD-L1 expression (AACR 2022) - "In addition, GH-targeting antibody-drug conjugate (ADC) OBI-999 has been demonstrated an excellent tumor growth inhibition potency in animal models across multiple cancer types including gastric cancer (GC)... GH level was associated with the survival of GC patients and positively correlated with cell surface PD-L1 expression in vitro. Therefore, GH-targeting therapy has a potential application for the treatment of GC patients."

Clinical • IO biomarker • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCND1 • CCNE1 • EGFR • PD-L1

OBI Pharma Enters License Agreement with Odeon Therapeutics for the Rights of OBI-999 and OBI-833 in China, Hong Kong and Macau (PRNewswire) - "OBI Pharma...and Odeon Therapeutics...have entered into an exclusive license agreement whereby OBI grants rights of OBI-999, a novel antibody-drug conjugate, and OBI-833, a therapeutic cancer vaccine, targeting the tumor antigen Globo H in China, Hong Kong and Macau to Odeon. Under the terms of the agreement, OBI will grant Odeon exclusive rights to develop, register and commercialize OBI-999 and OBI-833 for human cancer therapy in China, Hong Kong and Macao. Odeon will issue to OBI fully paid equity equivalent to US$ 12 million upon signing. OBI is eligible for development and commercialization milestones totaling up to US$ 188 million."

Licensing / partnership • Oncology

OBI Pharma Announces Phase 2 Studies Patient Enrollment for OBI-999 and OBI-3424 (PRNewswire) - "OBI Pharma...announced that the first patients have been enrolled in both of the Phase 2 studies of OBI-999, an antibody drug conjugate (ADC) cancer therapy targeting Globo H, and OBI-3424, a prodrug targeting the enzyme aldo-keto reductase 1C3 (AKR1C3)...The Phase 2 part of the study will enroll Globo H expressing patients with pancreatic, colorectal and other high Globo H expression solid tumors in more than ten medical centers in the United States and Taiwan. The Phase 2 cohort expansion part of the OBI-3424-001... This study will enroll AKR1C3 expressing patients with pancreatic and other high AKR1C3 expressing solid tumors in select oncology medical centers in the United States....OBI anticipates completing the enrollment of both Phase 2 studies in the second half of 2023."

Enrollment status • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor

Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=185; Recruiting; Sponsor: OBI Pharma, Inc; Active, not recruiting ➔ Recruiting

Clinical • Enrollment open • Colorectal Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • CD4 • MRI

[VIRTUAL] A phase I/II, open‑label, dose-escalation, and cohort-expansion study evaluating the safety, pharmacokinetics, and therapeutic activity of OBI‑999 in patients with advanced solid tumors. (ASCO 2020) - P1/2 | "OBI-999 is an ADC composed of a human recombinant immunoglobulin G (IgG) monoclonal antibody that selectively and specifically binds to GH, attached by a linker to the antimitotic agent monomethyl auristatin E (MMAE)...Patients must have GH overexpression defined as an H-score of ≥100 according to an FDA Investigational Device Exempt (IDE) validated IHC assay. Research Funding: OBI Pharma Inc."

Clinical • IO Biomarker • P1/2 data • PK/PD data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • Thoracic Cancer

Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=185; 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 • CD4 • MRI

[VIRTUAL] Globo H expression in metastatic colorectal cancer (CRC). (ASCO 2021) - "An attractive therapeutic target, Globo H-targeted agents are being tested in early clinical trials (e.g., OBI-833, a Globo H antigen conjugated to a mutated diphtheria toxin with potential antineoplastic activities, and OBI-999, an antibody-drug conjugate (ADC) consisting of a Globo H monoclonal antibody with a synthetic antineoplastic agent) . The association with TMB-H, MSI-H, and PD-L1 status suggests that in some tumors Globo H may be a promising target for combination therapy with immune checkpoint inhibition . The association with different cell populations suggests manipulating the cellular balance in the TME as an approach to improve the efficacy of treatment . NK cell checkpoint inhibitors are in clinical trials and might be utilized in high Globo H cancers; treatments inducing DCs in tumors have been shown to enhance responses to BRAF and PD-L1 blockade and might be applicable in the context of Globo H immunotherapy to overcome Treg immune suppression ."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Immune Modulation • Infectious Disease • Inflammation • Oncology • Solid Tumor • BRAF • CD4 • KRAS • MSI • MYC • RSPO3 • TMB

Pre-clinical Studies of OBI-999: a Novel Globo H-Targeting Antibody-Drug Conjugate. (PubMed, Mol Cancer Ther) - P1/2 | "The highest nonseverely toxic dose in cynomolgus monkeys is 10 mg/kg determined by a 3-week repeated-dose toxicology study demonstrating an acceptable safety margin. Taken together, these results support further clinical development of OBI-999, which is currently in a Phase 1/2 clinical study in multiple solid tumors (NCT04084366)."

IO biomarker • Journal • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

"#OBIPharma Announces OBI-999 Presentation at 2020 World ADC Digital Meeting https://t.co/RfIwIVc75p" (@1stOncology)

OBI Pharma Announces OBI-999 Presentation at 2020 World ADC Digital Meeting (PRNewswire) - "OBI Pharma, Inc...and chemotherapeutics targeting AKR1C3, today announced a scientific presentation will be held for OBI-999 (anti-Globo H targeted ADC) at the World ADC Digital Scientific meeting on Sept 16, 2020....The presentation will highlight the results from pre-clinical studies of OBI Pharma's first-in-class anti-Globo H antibody drug conjugate (OBI-999), including animal efficacy and safety data, supporting the ongoing Phase 1/2 human study ongoing at the MD Anderson Cancer Center in Houston, TX (USA)."

Preclinical • Oncology

Phase 1/2 Study of OBI-999 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1/2; N=185; Recruiting; Sponsor: OBI Pharma, Inc; Trial completion date: May 2023 ➔ Dec 2023; Trial primary completion date: Apr 2023 ➔ Nov 2023

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

OBI Pharma announces poster presentations at 2020 ASCO Virtual Annual Meeting for adagloxad simolenin, OBI-999 and OBI-3424 (PRNewswire) - "OBI Pharma, Inc…announced that data highlighting the ongoing clinical studies targeting Globo H and AKR1C3 antigen in different tumor types will be presented at the American Society of Clinical Oncology (ASCO) ASCO20 Virtual Scientific Program from May 29–31, 2020."

P1/2 data • P3 data • Breast Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer

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

"#OBIPharma Granted U.S. #FDA #OrphanDrugDesignation for the Treatment of #GastricCancer for Its #AntibodyDrugConjugate (#ADC) #TargetedCancerTherapy, #OBI999 https://t.co/ic9enWY2Pg" (@1stOncology)

Orphan drug

OBI Pharma granted U.S. FDA Orphan Drug Designation for the treatment of gastric cancer for its antibody-drug conjugate (ADC) targeted cancer therapy, OBI-999 (PRNewswire) - “OBI Pharma, Inc…announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for OBI-999 for the treatment of Gastric Cancer.”

Orphan drug

"#OBIPharma Granted #FDA #OrphanDrugDesignation for the Treatment of #PancreaticCancer for Its #AntibodyDrugConjugate (#ADC) Targeted #CancerTherapy, #OBI999 https://t.co/MXAfR0vruq" (@1stOncology)

Orphan drug