OBI-992 / OBI Pharma, Biosion - LARVOL DELTA

OBI Pharma Announces Poster Presentations at the AACR 2025 Annual Meeting for OBI-992 and OBI-902 Antibody-Drug Conjugates (ADCs), GlycOBI and ThiOBI ADC enabling technologies, the OBI-3424 prodrug, and Globo H (GH) science (GlobeNewswire) - "OBI Pharma, Inc...today announced nonclinical data for OBI-902, a potential best-in-class anti-TROP2 ADC developed using the next generation proprietary GlycOBI technologies. OBI-902 demonstrated superior antitumor activity and favorable PK/PD properties compared to benchmark TROP2 ADCs across various animal models. OBI-992...demonstrated a differentiated resistance profile compared to benchmark ADCs. Additionally, characterization and non-clinical in vivo data will be presented for the glycan-specific GlycOBI and cysteine-based ThiOBI proprietary ADC platforms, highlighting enhanced antitumor activity and stability in animal model studies. ThiOBI is a new next-generation platform and adds to OBI’s armamentarium of ADC enabling technologies. Additionally, the non-clinical and antitumor activity of OBI-3424, a novel AKR1C3 targeted prodrug, will be presented."

Preclinical • Solid Tumor

OBI-992, a novel TROP2 antibody-drug conjugate, exhibits distinct resistance profiles compared to other TROP2 targeting ADCs (AACR 2025) - "As a result, several antibody-drug conjugates (ADC) have been developed targeting TROP2, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd)... OBI-992, a novel TROP2 targeting ADC, emerges as a potential promising therapeutic option for patients who are resistant to other TROP2 targeting ADCs such as SG and Dato-Dxd. OBI-992 exhibits distinct resistance profiles compared to other TROP2 targeting ADCs. Understanding of potential mechanisms of resistance can provide potential combination options for TROP2-targeting ADCs to combat the drug resistance.Keywords: OBI-992, TROP2, antibody-drug conjugate, Colon cancer, resistance"

Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • ATRX • BRCA2 • MET • PALB2 • TOP1

Preclinical evaluation of a novel antibody-drug conjugate OBI-992 for Cancer therapy. (PubMed, Sci Rep) - "OBI-992, an investigational TROP2-targeted ADC, is composed of a novel TROP2 antibody (R4702) conjugated to the topoisomerase I (TOP1) inhibitor exatecan through a hydrophilic enzyme-cleavable linker...ADCs sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) were used as benchmarks for OBI-992...Moreover, substantial enhancement of cytotoxicity and DNA damage was found in the combination of OBI-992 with a poly (ADP-ribose) polymerase (PARP) inhibitor (talazoparib). Taken together, the findings in this study support further clinical development of OBI-992."

Journal • Preclinical • Breast Cancer • Oncology • Solid Tumor • TACSTD2 • TOP1

Preclinical evaluation of a novel antibody–drug conjugate OBI-992 for Cancer therapy (Nature, Sci Rep) - "The cytotoxicity of the OBI-992, SG, and Dato-DXd against different cancer cells is comparable despite they have different internalization profile. Upregulation of breast cancer resistance protein (BCRP) was observed in SG-resistant and Dato-DXd-resistant cells, but not in OBI-992-resistant cells. In addition, significant downregulation of TROP2 expression was detected with Dato-DXd-resistant cells and only slightly downregulation with SG- and OBI-992-resistant cells was observed."

Preclinical • Breast Cancer

Preclinical evaluation of a novel antibody–drug conjugate OBI-992 for Cancer therapy (Nature, Sci Rep) - "The cytotoxicity of the OBI-992, SG, and Dato-DXd against different cancer cells is comparable despite they have different internalization profile. Upregulation of breast cancer resistance protein (BCRP) was observed in SG-resistant and Dato-DXd-resistant cells, but not in OBI-992-resistant cells. In addition, significant downregulation of TROP2 expression was detected with Dato-DXd-resistant cells and only slightly downregulation with SG- and OBI-992-resistant cells was observed."

Preclinical • Breast Cancer

OBI-992, a Novel TROP2-Targeted Antibody-Drug Conjugate, Demonstrates Antitumor Activity in Multiple Cancer Models. (PubMed, Mol Cancer Ther) - "This study evaluated and compared the antitumor activity of OBI-992 with that of benchmark TROP2-targeted ADCs datopotamab deruxtecan (Dato-DXd) and sacituzumab govitecan (SG) in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models...The combination of OBI-992 at suboptimal doses with either poly (ADP-ribose) polymerase (PARP) inhibitors or an immune check point inhibitor produced synergistic antitumor effects in mouse models. Taken together, these translational results support further development of OBI-992 as a cancer therapy."

Journal • Preclinical • Breast Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • TACSTD2 • TOP1

Haoding will focus on the development of new ADC drugs in the next five years, and the second interim analysis of phase 3 clinical trials of new breast cancer drugs will be H1 next year. [Google translation] (stock.yahoo) - "...Chen Jialing...pointed out that the Phase III clinical trial of Haoding’s new active immune anti-cancer drug adagloxad simolenin (AdaSim/OBI-821) passed the first interim analysis at the beginning of this year. Due to the conditions of the interim analysis, Based on the number of patient disease recurrence or death events; this trial expired last week with 113 events. After another three to four months of data cleaning and re-confirmation, AdaSim is expected to hold a data and safety conference in the first half of 2025. At the second interim analysis meeting of the Data and Safety Monitoring Board (DSMB), the company has begun to prepare for future new drug applications (BLA)....In addition, OBI-992...started clinical trials in June....With the active participation of clinical trial hosts in the United States and Taiwan, it was completed in just 14 weeks. The safety and dose evaluation of the two groups of patients are currently entering the third group of research stages."

P3 data • Trial status • Breast Cancer • Oncology • Solid Tumor

Haoding launched a five-year new drug plan [Google translation] (China Times) - "Haoding launched a five-year new drug development plan...it is expected that the final analysis and application for drug certification of the third phase of the OBI-822 clinical trial will be completed in 2029, the second phase of the OBI-992 clinical trial will be completed, the clinical trial of GlycOBI-related products will be started, and the external licensing cooperation opportunities will be accelerated...The Phase III clinical trial of OBI-822, which has attracted the most attention, is expected to undergo a second interim analysis at the end of the year, and will successfully reach event unblinding in 2026."

New P3 trial • Trial status • Breast Cancer • Oncology • Solid Tumor

Haoding OBI-992 was shortlisted for the World ADC Award and became the most potential clinical drug candidate in 2024 [Google translation] (stock.yahoo) - "Taiwan's Optoelectronics...announced today (24th) that its Antibody-Drug Conjugate (ADC) anti-cancer drug OBI-992 won the '11th World ADC Award' Favored, stood out among more than 1,000 nominees and was shortlisted as the 'Most Potential Clinical Drug Candidate in 2024'; a total of eight candidate drugs were nominated, and an expert jury will select the champion and runner-up, which are expected to be announced at the World ADC Conference in November winner...It is expected to be held in San Diego, California, USA on November 6, 2024. The competition will be held and the winner will be announced at that time...M. Wayne Saville....pointed out that from preclinical experiments, OBI-992 has several important advantages compared with other TROP2 ADCs that have been approved or under development, such as high stability in blood, Cancer cells without TROP 2 expression also have a clear and effective 'bystander effect' that can kill neighboring TROP2-negative cancer cells."

Clinical • Preclinical • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor

Haoding OBI-992 TROP2 ADC new drug was approved by the United States Food and Drug Administration as an ’orphan drug’ for the treatment of gastric cancer [Google translation] (Yahoo Finance) - "The new drug OBI-992 TROP2 ADC was approved by the United States Food and Drug Administration as an 'orphan drug' for the treatment of gastric cancer...Major events in drug research and development: The company received a letter from the United States Food and Drug Administration (US FDA) and passed the review Orphan Drug Designation for OBI-992 TROP2 ADC. The symptoms are gastric cancer, including gastroesophageal junction cancer."

Orphan drug • Gastric Cancer • Gastroesophageal Cancer • Oncology • Solid Tumor

A Phase 1/2 Study of OBI-992 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1/2 | N=117 | Recruiting | Sponsor: OBI Pharma, Inc

Metastases • New P1/2 trial • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

In vitro characterization of a novel TROP2-targeting antibody-drug conjugate OBI-992 (AACR 2024) - "Sacituzumab govitecan, a TROP2 ADC conjugated to topoisomerase inhibitor (TOP1) SN-38, has been approved for patients with triple-negative breast cancer. This study aims to investigate the characteristics of a novel TROP2 antibody (R4702) and its ADC OBI-992, which is derived from the conjugation of R4702 with a TOP1 inhibitor exatecan.METHODSClinical study: Prognostic roles of TROP2 and TOP1 in patients were accessed through the "Kaplan-Meier plotter" database from more than 1055 colon cancer patients.In vitro study: An ELISA study was conducted to investigate the binding epitope of R4702...Finally, a synergistic effect of OBI-992 and PARP inhibitors (talazoparib, rucaparib, niraparib, and olaparib) on the enhancement of cancer cell killing and DNA damage was observed.CONCLUSIONHigh expression of both TROP2 and TOP1 is associated with poor survival in patients with colon cancer...Exatecan and exatecan-conjugated ADC OBI-992 showed high cytotoxic activities...."

Preclinical • Breast Cancer • Colon Cancer • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Oncology • Pancreatic Cancer • Prostate Cancer • Solid Tumor • Triple Negative Breast Cancer • TACSTD2 • TOP1

OBI Pharma Announces Phase 1/2 Study Initiation for OBI-992, a TROP2-Targeted Antibody-Drug Conjugate (ADC) for Cancer Therapy (GlobeNewswire) - "OBI Pharma...announced the initiation of a Phase 1/2 clinical trial of OBI-992, an antibody-drug conjugate (ADC) targeting TROP2 (Trophoblast cell-surface antigen 2), an antigen overexpressed in multiple tumor types. OBI plans to enroll patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), gastric cancer (GC), and other potential cancers. The objective of the trial is to verify the safety, pharmacokinetics, and preliminary efficacy profile of OBI-992 in these patient populations."

New P1/2 trial • Gastric Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Haoding: Our company’s new drug OBI-992 TROP2 ADC has submitted a Phase I/II human clinical trial application to the Food and Drug Administration of Taiwan’s Ministry of Health and Welfare. [Google translation] (Anue Juheng) - "OBI-992 TROP2 ADC was submitted to the Food and Drug Administration of the Ministry of Health and Welfare of Taiwan for Phase I/II human clinical trials....Estimated completion time: The first phase of the dose escalation trial is expected to be completed in the first half of 2025, but the actual schedule will depend on the implementation progress."

New P1/2 trial • Oncology • Solid Tumor

OBI-992, a novel TROP2 targeting antibody-drug conjugate, displayed excellent antitumor efficacy in various animal models (AACR 2024) - "OBI-992 in combination with PARP inhibitors such as olaparib and talazoparib was examined for potential synergistic effects in a homologous recombination deficiency (HRD) xenograft model. The cytotoxicity of OBI-992 was positively associated with the TROP2 RNA levels in different cell lines... OBI-992 exhibited excellent antitumor efficacy and outperformed the benchmark Dato-DXd in CDX and PDX models of various cancer types. A strong bystander killing effect indicated that OBI-992 will be effective for tumors with heterogenous expression of target antigen. OBI-992 retained its antitumor effect upon overexpression of Pgp and BCRP, suggesting that OBI-992 may overcome the multidrug resistance."

Preclinical • Breast Cancer • Oncology • Solid Tumor • CTSB • HRD • TACSTD2

OBI-992, a novel TROP2 targeting antibody drug conjugate demonstrates superior in vivo PK/PD properties and a favorable safety profile (AACR 2024) - "In vivo PK evaluation in rats showed that OBI-992 had lower Cmax and AUC of free payload than Dato-DXd, indicating a better PK profile of OBI-992 in rats... OBI-992 exhibits remarkable antitumor efficacy and a favorable safety profile, supporting further clinical development of OBI-992 in TROP2 positive cancers."

PK/PD data • Preclinical • Lung Cancer • Oncology • Solid Tumor

OBI Pharma Announces Poster Presentations at the AACR 2024 Annual Meeting for OBI-992 and GlycOBI ADC platform (GlobeNewswire) - "Our data suggest OBI-992 has the potential to become a best-in-class TROP2 ADC. OBI-992 binds to a TROP2 epitope that is distinct from that of datopotamab and sacituzumab. OBI-992 shows lower non-specific binding, which should lead to decreased off-target cytotoxicity compared to benchmark ADCs. OBI-992 demonstrated remarkable anti-tumor efficacy in several CDX and PDX models. In addition, OBI-992 showed excellent bystander effect and synergistic efficacy in combination with PARP inhibitors or anti-PD1 in animal models."

Preclinical • Solid Tumor

OBI PHARMA TO PRESENT THE STUDY RESULTS OF OBI-992 AT THE 14TH WORLD ADC LONDON (OBI Pharma Press Release) - "OBI Pharma is excited to announce that Dr. Ming-Tain Lai, Chief Scientific Officer, has been invited to present an oral presentation at the upcoming 14^th World ADC conference in London, United Kingdom...Dr. Lai will be presenting at a Speaker Session on Thursday, March 14, 2024 at 2:30 PM London time. He will share the following: Exploring the in vitro characterization of the ADC; Discussing in vivo animal efficacy studies of the ADC; Analyzing the pharmacokinetics/pharmacodynamics of the ADC...OBI-992 is a TROP2-targeted ADC that carries a potent topoisomerase I inhibitor payload to kill tumor cells....The Phase 1/2 efficacy and safety human studies are planned to commence Q2, 2024."

New P1/2 trial • Preclinical • Oncology • Solid Tumor

OBI-992: A TROP-2 ADC With Distinct Properties (ADC London 2024) - "Exploring the in vitro characterisation of the ADC • Discussing in vivo animal efficacy studies of the ADC • Analysing the pharmacokinetics/ pharmacodynamics of the ADC"

OBI Pharma Announces U.S. FDA Clearance of IND Application for a Phase 1/2 Study of OBI-992 (GlobeNewswire) - "OBI Pharma...announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for OBI-992, to conduct a Phase 1/2 study of its novel antibody - drug conjugate (ADC) cancer therapy targeting TROP2. OBI plans to enroll patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and gastric cancer (GC), although several other cancers are also potential targets....'We look forward to dosing the first patient in our Phase 1/2 clinical study of OBI-992, which is expected to begin in early 2024'."

IND • New P1/2 trial • Gastric Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Biosion's Partner OBI Pharma Announces FDA Clearance of IND Application for a Phase 1/2 Study of OBI-992 (TROP2 ADC) (PRNewswire) - "The Partner of Biosion Inc. (Biosion) , OBI Pharma...announced that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for OBI-992, to conduct a Phase 1/2 study of its novel antibody drug conjugate (ADC) cancer therapy targeting TROP2....OBI Pharma plans to enroll patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and gastric cancer (GC), although several other cancers are also potential targets....'We look forward to dosing the first patient in our Phase 1/2 clinical study of OBI-992, which is expected to begin in early 2024'."

IND • New P1/2 trial • Gastric Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

[Announcement] Haoding OBI-992 TROP2 ADC new drug has submitted Phase I/II human clinical trial application to the U.S. Food and Drug Administration (FDA) [Google translation] (stock.yahoo) - "Haoding OBI-992 TROP2 ADC new drug submitted Phase I/II human clinical trial application to the U.S. Food and Drug Administration (FDA)...OBI-992 is a new antibody drug conjugate (ADC) designed with TROP2 as the target, for cancer treatment....Estimated completion time: It is expected to be completed in 2024, but the actual timetable will be adjusted according to the implementation progress."

IND • New P1/2 trial • Trial completion date • Oncology