In the field of bispecific antibody cancer drugs, where global pharmaceutical companies such as Bristol-Myers Squibb (BMS) and Regeneron have withdrawn, domestic corporations are increasing their presence. Bispecific antibodies target both cancer cells and immune cells simultaneously, resulting in high anticancer efficacy, but development is complex, leading to high failure rates. Global pharmaceutical companies have also abandoned development due to increased difficulty, while domestic companies have achieved good results in clinical trials and even exported technology.
According to the pharmaceutical and bio industry on the 8th, domestic corporations such as ABL Bio and Yuhan Corporation are achieving results one after another in the bispecific antibody cancer drug sector, accelerating their development.
Bispecific antibodies act on both cancer cells and immune cells known as T cells. One hand delivers an uppercut to the cancer cell while simultaneously pulling the T cell with the other hand to induce a joint attack on the cancer cell. The dual attack results in higher anticancer efficacy. According to the global market research firm RootsAnalysis, the bispecific antibody market is projected to grow from 7.8 trillion won last year to 23.3772 trillion won by 2035.
However, there are drawbacks as the development is challenging and time-consuming. Since it must connect antibodies that target specific cancer cells and immune cells, it is difficult to maintain a stable structure compared to single antibodies. Global pharmaceutical companies entered development seeing market growth potential, but they faced such limitations.
Last year, BMS planned to conduct Phase 2 clinical trials of a bispecific antibody drug candidate introduced from the bio company Agenus on solid tumor patients but returned it. The reason was a reorganization of the pipeline (candidate substance group) for cost reduction. BYON, which developed a COVID-19 vaccine in partnership with the U.S. pharmaceutical company Pfizer, also halted bispecific antibody cancer drug development. Regeneron's 'odronextamab,' which was developed as a treatment for blood cancer, applied for approval from the U.S. Food and Drug Administration (FDA) but was rejected.
In contrast, domestic companies are accelerating their efforts. ABL Bio is a representative example. The company announced the main results of a global Phase 2/3 trial of 'tobesimimab,' a bile duct cancer treatment being developed in partnership with the U.S. company Compass Therapeutics. The objective response rate (ORR), which measures the proportion of patients showing objective responses including tumor size reduction, was confirmed to be 17.1%, over 10 percentage points higher than the control group (5.3%).
Tobesimimab is a bispecific antibody drug candidate that simultaneously targets vascular endothelial growth factor A (VEGF-A), which helps the growth of cancer, and delta-like ligand 4 (DLL4), which aids the growth of blood vessels in tumors. It was designated as a fast track for expedited review and approval by the U.S. FDA last year. Compass, which holds global rights, plans to announce additional clinical trial data, including key secondary endpoints, in the fourth quarter of this year and apply for accelerated drug approval.
ABL Bio also publicly released the preclinical results of the Parkinson's disease candidate substance 'ABL301,' which was licensed to Sanofi in 2022, on the 8th. According to the company, ABL301 showed improvements in the loss of nerve cells (neurons) and behavioral defects in Parkinson's disease patients in this preclinical study.
ABL301 is a bispecific antibody candidate substance using the independently developed blood-brain barrier penetration technology 'GrabBody-B.' The blood-brain barrier protects the brain from foreign substances but also blocks protein therapeutics like antibodies. GrabBody-B is the technology that the company licensed to GlaxoSmithKline (GSK) the previous day for a scale of 4 trillion won, and it can transport antibodies into the brain to enhance therapeutic effects. A Phase 1 clinical trial is currently underway, with results expected to be announced around mid-year.
ABL Bio is also developing an antibody-drug conjugate (ADC) that targets the protein PD-L1, which disguises cancer cells as normal cells, and the immune protein 4-1BB simultaneously. ADCs are therapeutic technologies that attach drugs to antibodies to precisely deliver them only to cancer cells. ABL Bio is developing 'ABL503,' a bispecific antibody ADC, in collaboration with the U.S. NASDAQ-listed company iMap Biopharma. A Phase 1 trial is currently ongoing, and if successful, it will become the first bispecific antibody ADC.
Yuhan Corporation also received approval from the Ministry of Food and Drug Safety for the investigational new drug application (IND) for 'YH32364,' which is being developed as an immuno-oncology agent, the previous day. YH32364 targets both epidermal growth factor receptor (EGFR), which is necessary for cancer growth and proliferation, and the immune protein 4-1BB.
4-1BB is expressed in various immune cells, including T cells, natural killer (NK) cells, and dendritic cells (DC). Yuhan Corporation's bispecific antibody aims to inhibit cancer cell growth while simultaneously promoting immune responses. The company plans to evaluate safety, tolerability, pharmacokinetics, and antitumor activity in patients with locally advanced or metastatic solid tumors confirmed to have EGFR overexpression in this Phase 1/2 trial of YH32364.