adagloxad simolenin (OBI 822) / OBI Pharma - LARVOL DELTA

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's new anti-cancer drug OBI-822 has applied for Phase 3 human clinical trials in Spain and three other countries - Finance - Industry and Commerce [Google translation] (feiyangjs.com) - "After being acquitted in the insider case, Horizon Biotechnology...also accelerated the development and licensing of new drugs! On the 17th, it announced that its active immune anticancer drug OBI-822 (Adagloxad Simolenin) had submitted an application to the European Medicines Agency (EMA) for Phase III human clinical trials in Spain, Germany and Poland, and it is expected that the main trial indicators will be evaluated in 2025...According to the agreement, Optimer will start the Phase III human clinical trial and must pay Optimer, a US company, a research and development milestone payment of US$1 million....OBI-822 is an active immune anticancer drug that targets the sugar antigen Globo H."

Licensing / partnership • New P3 trial • Breast Cancer • Oncology • Solid Tumor

Haoding OBI-822/821 second interim analysis at the end of the year, blinding will be solved at the beginning of 2026 [Google translation] (MoneyDJ) - "Haoding...pointed out that the OBI-822/OBI-821 phase III clinical trial targeting early-stage high-risk GloboH-positive breast cancer patients is expected to meet the conditions for the second interim analysis before the end of this year (2024) and to meet the unblinding conditions in early 2026., and it is also planned to open up immune checkpoint PD-1 inhibitors as one of the standard care organizations....Chen Jialing, director of the product development team of Haoding, said that the original plan of the trial was to admit 668 patients, and the incidence of events such as recurrence or death was used as the condition for interim analysis. The first interim analysis of 75 events occurred, and it has been completed in early 2024. Reached, the second interim analysis showed that 113 people reached the target after the incident, and there should be a chance before the end of 2024."

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

Potential role and prognostic value of Globo-H in lung cancer. (ASCO 2024) - "Clinical trials have been conducted to evaluate the efficacy of anti-GH vaccine Adagloxad Simolenin/OBI-821 (in Ph 3) and OBI-833/OBI-821 (in Ph 2) in cancer patients. GH expression was associated with the worse survival of LC patients in clinical setting. In addition, the level of GH is positively correlated with levels of EGFR and EGFR-related signaling proteins in vitro. Expression of GH can induce the expression of EGFR and vice versa in LC cells."

IO biomarker • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CCND1

Focus stocks: Haoding’s multiple R&D new drugs are advancing in clinical trials, and the first interim analysis of OBI 822/821 Phase III is positive [Google translation] (stock.yahoo) - "...Yesterday (31st), it announced its new active immune drug OBI-822/821 as an adjuvant treatment for post-surgery surgery A phase III clinical trial for patients with early-stage, Globo H-positive, high-risk triple-negative breast cancer received a positive response from the Data and Safety Monitoring Board (DSMB) for the first (75 cases) interim analysis of this clinical trial (113 cases will be reviewed after receipt of 113 cases) Conducting the second interim analysis), it is recommended that the trial continue; this will add points to Haoding's chance of success."

DSMB • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Heat-shock protein 90α protects NME1 against degradation and suppresses metastasis of breast cancer. (PubMed, Br J Cancer) - "These results not only reveal a new mechanism of NME1 degradation but also pave the way for the development of new and effective approaches to metastatic cancer therapy."

Journal • Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • HSP90AA1

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

A phase 3, randomized, open-label study of the anti-Globo H vaccine adagloxad simolenin/obi-821 in the adjuvant treatment of high-risk, early-stage, Globo H-positive triple-negative breast cancer. (ASCO 2022) - P3 | "SOC in the A-S/OBI-821 arm is concomitant therapy of capecitabine or immune checkpoint inhibitor. An estimated 668 subjects will be enrolled, treated for up to 2 years, and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject."

Clinical • IO biomarker • P3 data • Breast Cancer • Immune Modulation • Inflammation • Oncology • Solid Tumor • Triple Negative Breast Cancer

GLORIA: phase III, open-label study of adagloxad simolenin/OBI-821 in patients with high-risk triple-negative breast cancer. (PubMed, Future Oncol) - "In a phase II study, adagloxad simolenin (AdaSim), a synthetic Globo H conjugate vaccine administered with adjuvant OBI-821, was shown to induce IgM and IgG anti-Globo H humoral responses in patients with metastatic breast cancer overexpressing the glycosphingolipid Globo H. GLORIA is an ongoing phase III, randomized, open-label clinical trial to evaluate the safety and efficacy of AdaSim and the quality of life (QoL) of patients receiving AdaSim plus standard of care (SOC) versus SOC alone in high-risk, early-stage TNBC. The primary end point is invasive progression-free survival; secondary end points include overall survival, QoL, breast cancer-free interval, distant disease-free survival, safety, and tolerability."

Journal • P3 data • Review • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

The clinical relevance of humoral immune responses to Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 and expression of Globo H in metastatic breast cancer. (PubMed, J Immunother Cancer) - "This study demonstrates that adagloxad simolenin induced both IgG and IgM antibodies against GH. Anti-GH IgM ≥1:320 within first 4 weeks or low activated Treg cells at baseline may help to select patients who are likely to produce a higher level of GH-specific IgM and IgG in the future."

Journal • Breast Cancer • Oncology • Solid Tumor

Globo H: A Globo series glycosphingolipid target antigen in breast cancer (SABCS 2021) - "Adagloxad simolenin (AS/OBI-822) is a Globo H conjugate vaccine that when administered in combination with the adjuvant OBI-821 results in anti‒Globo H IgM and IgG humoral immune responses...To enter the GLORIA study, patients must have a centrally confirmed Globo H IHC H-score of ≥15, and it is anticipated that approximately 40% of patients screened will have this level of expression. The GLORIA study is presently enrolling patients in 7 countries, with another 9 countries anticipated to begin recruiting in 2021."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CAV1 • NOTCH1

Humoral immune responses elicited by Globo H vaccine and the impact of Globo H expression levels on clinical response to Globo H vaccine in metastatic breast cancer (SITC 2018) - P3; "Notably, in the vaccinated group, immune nonresponders produced equivalent levels of anti-KLH antibody as immune responders, suggesting a similar capacity to respond to foreign antigens. A trend for better PFS in subjects with higher GH expression 307 treated with OBI-822/821 versus placebo suggests the need for pre-screening GH expression in future trials of OBI-822/821."

Biomarker • Clinical • Breast Cancer • Hormone Receptor Breast Cancer

Phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of adagloxad simolenin (OBI-822) and OBI-821 treatment in patients with early-stage triple-negative breast cancer (TNBC) at high risk for recurrence (SABCS 2019) - "Patients will be treated for up to 2 years and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last patient randomized. Survival follow-up is for 5 years from randomization of last patient."

Clinical • P3 data • ER • HER2 • PGR

Adagloxad Simolenin/OBI-821 in Combination With TACE Therapy in HCC Patients With GALNT14-rs9679162-non-TT Genotype (clinicaltrials.gov) - P2; N=5; Terminated; Sponsor: Chang Gung Memorial Hospital; N=51 ➔ 5; Recruiting ➔ Terminated; The biopsies in the first 5 screened patients were all negative for Globo-H, of which positive is required to include the patients.

Clinical • Combination therapy • Enrollment change • Trial termination • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor

Study of Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients With Globo H Positive TNBC (clinicaltrials.gov) - P3; N=668; Recruiting; Sponsor: OBI Pharma, Inc; Trial completion date: Nov 2025 ➔ Dec 2027

Clinical • Trial completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2 • PGR

Globo H-KLH vaccine adagloxad simolenin (OBI-822)/OBI-821 in patients with metastatic breast cancer: phase II randomized, placebo-controlled study. (PubMed, J Immunother Cancer) - P2 | "AS/OBI-821 did not improve PFS in patients with previously treated MBC. However, humoral immune response to Globo H correlated with improved PFS in AS/OBI-821 recipients, leading the way to further marker-driven studies. Treatment was well tolerated.NCT01516307."

Clinical • Journal • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

[VIRTUAL] Phase III, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of adagloxad simolenin (OBI-822) and OBI-821 treatment in patients with early-stage triple-negative breast cancer (TNBC) at high risk for recurrence. (ASCO 2020) - "Survival follow-up is for 5 years from randomization of last subject. Research Funding: OBI Pharma Inc."

Clinical • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

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

Phase 2 clinical results of a carbohydrate (GloboH)-based cancer vaccine (ACS-Sp 2018) - "The most common adverse events reported for OBI-822/OBI-821 treated patients were grade 1 or 2 injection site reactions (56.7%) and pyrexia (20.1%) compared to the placebo group (8.9% and 6.5%, respectively).In conclusion, the vaccine-treated patients who had a humoral immune response to the Globo H antigen correlated highly with improved PFS when compared to those who did not have a humoral immune response or those who received placebo. Work is in progress to design a phase III trial."

Clinical • P2 data • Biosimilar • Breast Cancer • Hormone Receptor Breast 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

Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy. (clinicaltrials.gov) - P3; N=668; Not yet recruiting; Sponsor: OBI Pharma, Inc

Clinical • New P3 trial

Study of Adagloxad Simolenin (OBI-822) and OBI-821 Versus Placebo Treatment for High Risk Early Stage Triple Negative Breast Cancer Patients (TNBC) Following Neoadjuvant or Adjuvant Chemotherapy. (clinicaltrials.gov) - P3; N=668; Recruiting; Sponsor: OBI Pharma, Inc; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open

Adagloxad Simolenin/OBI-821 in Combination With TACE Therapy in HCC Patients With GALNT14-rs9679162-non-TT Genotype (clinicaltrials.gov) - P2; N=51; Recruiting; Sponsor: Chang Gung Memorial Hospital; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open

Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Metastatic Breast Cancer Subjects (clinicaltrials.gov) - P2; N=349; Completed; Sponsor: OBI Pharma, Inc; Active, not recruiting ➔ Completed

Clinical • Trial completion