barecetamab (ISU104) / ISU Abxis - LARVOL DELTA

ISU Abxis, ISU104·CAR-NK Breast Cancer Mouse Tumor Size Reduction Confirmed [Google translation] (BioNews) - "Isu Abxis announced on the 10th that it confirmed the therapeutic efficacy of its treatment combining its targeted anticancer treatment candidate 'ISU104' with CAR-NK technology in reducing tumor size in mice transplanted with breast cancer cell lines...In an animal experiment utilizing a model in which breast cancer cell lines were transplanted into mice, ISU104·CAR-NK showed anticancer efficacy, reducing tumor size without any particular side effects....'The research results suggest that ISU104·CAR-NK targeting ErbB3 may be an effective immunotherapy for patients with ErbB3-positive breast cancer who are resistant to or do not respond to existing treatments, and demonstrate the potential for an innovative treatment strategy utilizing cutting-edge regenerative medicine.'"

Preclinical • Breast Cancer • ERBB3

Isu Abix records highest sales and profits in the first half of the year… “Thanks to increased sales from technology transfer” [Google translation] (Nate) - "Isu Abxis...recorded its best performance since its establishment in the first half of the year with sales of KRW 30.9 billion and operating profit of KRW 8 billion....Sales related to the technology transfer of ISU104 and ISU106, worth KRW 4.8 billion, also contributed significantly. Isu Abxis transferred the technology of ISU104 to a U.S. anticancer drug development company in June, and of the initial contract deposit of USD 3 million (approximately KRW 4.2 billion), USD 2 million (approximately KRW 2.8 billion) was recognized first in the second quarter, as per the contract."

Sales • Breast Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • Oncology • Solid Tumor

Isu Abxis Transfers Anticancer Drug Technology to US-based Company [Google translation] (MSN News) - "Isu Abxis...announced on the 26th that it signed a contract to transfer technology for the new anticancer drug 'ISU104' (ingredient name: varcetamab) to an anticancer drug development company located in the United States. The contract amount is 3 million dollars (approximately 4.1 billion won), and up to 85.5 million dollars (approximately 120 billion won) can be received, including stage-by-stage technology fees (milestones) based on development, approval, and sales achievement. Isu Appxis said that it does not disclose information on companies with which it has signed contracts in order to maintain business confidentiality."

Licensing / partnership • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

“Isu Abix, additional technology exports expected in the second half of the year” [Google translation] (eDaily) - "There are voices in the financial investment industry mentioning the possibility of additional technology export contracts for Isu Abxis (086890) as early as the second half of this year...Previously, Isu Abxis succeeded in exporting technology for ISU-104 (ingredient name: barcetamab) to a U.S.-based anticancer drug company....It expected that the technology export advance payment for ISU-104 would be reflected in the second and third quarters."

Financing • Breast Cancer • Colon Cancer • Head and Neck Cancer • Oncology • Solid Tumor

ISU Abxis exports 'Barecetamab' worth KRW 120 billion to a US anticancer drug development firm [Google translation] (BioNews) - "Abxis has secured a technology export contract valued at KRW 120 billion (approximately USD 86.3 million) for 'ISU104 (development code name, barecetamab)', a novel anti-cancer drug candidate...ISU Abxis announced on June 26 that it had signed a USD 88.5 million (approximately KRW 118.5 billion) technology export agreement for ISU104 with a US-based anticancer drug development company. The contract is effective from the signing date until the end of the sale. For confidentiality reasons, the identity of the contracting party will remain undisclosed....The agreement includes a non-refundable upfront payment of USD 3 million. It also includes milestone (technology fees for each stage) payments for various stages, including the US clinical application, phase 2 and phase 3 clinical trials, and product approval. In addition, the contract includes sales milestones after product approval, with royalty payments based on net sales after commercialization."

Licensing / partnership • Breast Cancer • Colorectal Cancer • Head and Neck Cancer • Oncology • Solid Tumor

[Newspim LaCiro] ISU Abxis “Goal for technology transfer of ‘ISU104’ and ‘ISU203’ within the year” [Google translation] (Nate) - "Isu Abxis, a biotech specializing in rare disease treatments, is aiming to transfer technology for new drug candidates within the year. This year, the strategy is to continue the surplus trend by expanding overseas markets and secure external expansion through technology transfer....The new drug candidates that Isu Abxis is currently exploring for technology transfer include an anti-cancer antibody treatment (ISU104) and an Alzheimer's treatment (ISU203)."

Licensing / partnership • Alzheimer's Disease • CNS Disorders • Oncology • Solid Tumor

Isu Abxis, first quarter operating profit of KRW 3.2 billion… 144% increase in sales [Google translation] (eDaily) - "An ISU Abxis official said, 'We expect top-line and profit growth to continue due to the expansion of overseas exports,' adding, 'At the same time, we are also pursuing overseas licensing out (LO) of anti-cancer antibody treatment ISU104 and Alzheimer’s treatment ISU203 as a key task, so this year, we will focus on research and development (R&D), he said, 'and we will also achieve results.'"

Licensing / partnership • Alzheimer's Disease • Oncology • Solid Tumor

Isu Abxis publishes the results of phase 1 clinical study of innovative new drug 'ISU104' in the International Cancer Journal [Google translation] (Medifonews) - P1 | N=33 | NCT03552406 | Sponsor: ISU Abxis Co., Ltd. | "Isu Abxis announced...that the results of the phase 1 clinical study of ISU104...were published in The International Journal of Cancer....In the phase 1 clinical study...it was particularly encouraging that one oral cancer patient achieved complete remission among 11 patients with ISU104 and cetuximab (EGFR treatment) combination therapy in Part 2. This lasted more than 17 months at the time of analysis. In addition, partial remission was confirmed in two patients with laryngeal cancer, and the objective response rate (ORR) reached 36.4%. Side effects were similar to the toxicity profile of cetuximab and were manageable. In addition, through biomarker analysis, the TP53 gene mutation, which frequently occurs in most cancers, was identified in complete and partial response patients. In particular, one patient who showed complete remission had EGFR amplification."

P1 data • Oncology • Solid Tumor

A phase Ia/Ib study of novel anti-ErbB3 monoclonal antibody, barecetamab (ISU104) in refractory solid cancers and monotherapy or in combination with cetuximab in recurrent or metastatic head and neck cancer. (PubMed, Int J Cancer) - "The recommended phase II dose was determined to be 20 mg/kg triweekly. Barecetamab and in cetuximab combination was well tolerated and demonstrated meaningful antitumor effects."

Combination therapy • Journal • Metastases • Monotherapy • P1 data • Dental Disorders • Dermatitis • Dermatology • Head and Neck Cancer • Immunology • Oncology • Solid Tumor • Squamous Cell Carcinoma • Stomatitis • ERBB3

[VIRTUAL] Final results and biomarker analysis from a phase I dose-expansion (part II) study of ISU104 (barecetamab; a novel anti-ErbB3) monotherapy or in combination with cetuximab (CET), in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (ESMO 2021) - P1 | "ISU104 alone or in combination with CET were safe and tolerable in R/M HNSCC pts. Encouraging clinical efficacies and potential biomarkers were demonstrated from combination therapy. A phase II study of ISU104 (Q3W, 20 mg/kg/day) in combination with CET (Q1W) is planned to further strengthen the clinical utility of ISU104."

Biomarker • Clinical • Combination therapy • Monotherapy • P1 data • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • ERBB3 • TP53

[VIRTUAL] Phase I dose-expansion (part II) study of ISU104 (a novel anti-ErbB3 monoclonal antibody) alone and combination with cetuximab (CET), in patients (pts) with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) (ESMO 2020) - "Legal entity responsible for the study: ISU Abxis Co., Ltd. Funding: Korea Drug Development Fund."

Clinical • P1 data • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EGFR • ERBB3 • HER-2 • NRG1

First in human, a phase I study of ISU104, a novel ErbB3 monoclonal antibody, in patients with advanced solid tumours (ESMO 2019) - P1; "Intravenous administrations of ISU104 were well tolerated up to 20 mg/kg/day without DLT, and showed disease control rate of 60.0%. Safety and efficacy of ISU104 as mono- or combination-therapy and potential biomarkers will be further explored in head and neck, colorectal and breast cancers. Clinical trial identification: NCT03552406."

Clinical • P1 data

Study of ISU104, Targeting ERBB3 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=33; Active, not recruiting; Sponsor: ISU Abxis Co., Ltd.; Recruiting ➔ Active, not recruiting; Trial completion date: Dec 2020 ➔ Dec 2021; Trial primary completion date: Jul 2020 ➔ Oct 2020

Clinical • Enrollment closed • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma

A novel therapeutic anti-ErbB3, ISU104 exhibits potent anti-tumorigenic activity by inhibiting ligand binding and ErbB3 heterodimerization. (PubMed, Mol Cancer Ther) - "The anti-cancer efficacy of ISU104 was demonstrated in xenograft models of various cancers. In summary, a highly potent ErbB3 targeting antibody ISU104 is suitable for clinical development."

Journal • Oncology • ERBB3 • HER-2 • NRG1

[VIRTUAL] Anti-cancer efficacy of an anti-ErbB3 antibody, ISU104, against the cancers with NRG1-overexpression, NRG1-fusion, or oncogenic ErbB3 mutations (AACR-II 2020) - "Potential impacts of other genetic alterations on the anti-cancer efficacy of ISU104 were also investigated. Overall, the presented data suggest that ISU104, an anti-ErbB3 agent in the early stage of clinical development, can be applied for the treatment of the solid tumors expressing high level of NRG1 or harboring genetic alterations such as NRG1-fusion or oncogenic ErbB3 mutations."

Clinical • Oncology • Solid Tumor • ERBB3 • HER-2 • NRG1

ISU Abxis releases preclinical trial results for anticancer antibody (Korea Biomedical Review) - "ISU Abxis has presented the preclinical trial results for ISU104, an anti-ErbB3 antibody biomarker against the cancers with Neuregulin 1 (NRG1)-overexpression, NRG1-fusion, or oncogenic ErbB3 mutations, at the American Association for Cancer Research 2020 conference....ISU Abxis completed the recruitment of patients for its phase 1 clinical trial to confirm the efficacy of ISU104 in March and plans to announce the final trial results early next year."

Enrollment closed • P1 data • Preclinical • Oncology • Solid Tumor

Study of ISU104, Targeting ERBB3 in Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1; N=33; Recruiting; Sponsor: ISU Abxis Co., Ltd.; N=55 ➔ 33

Enrollment change

ISU Abxis to unveil p1 results for anticancer treatment in Europe (Korea Biomedical Review) - "ISU Abxis will present its phase 1 clinical trial data for ISU104, an Erb-B2 Receptor Tyrosine Kinase 3 (ErbB3) target anti-cancer drug....ISU Abxis is also preparing to conduct part 2 of phase 1 clinical trial."

P1 data

ISU Abxis confirms safety profile for immunotherapy candidate (Korea Biomedical Review) - “ISU Abxis has published an interim report confirming the safety profile for ISU104…The report came after the company held a steering committee as it has finished recruiting patients for Part 1 of the drug’s phase 1 clinical trial...Part 2, which begins in the second half of the year, will include about 40 patients...Participating in the trial are patients with end-stage advanced solid cancer who were resistant to standard therapy or who had no standard treatment....The company plans to evaluate the safety, efficacy, tolerability, and pharmacokinetics in phase 1 clinical trials. Isu Abxis plans to complete the trial by 2020.”

Enrollment status • New P1 trial • Trial status