K-biopharma starts trials with bispecific antibodies

Hanmi Pharm’s immunotherapy candidate targeting ’PD-L1·41BB’ has entered Phase 1

ABL Bio secured efficacy in the clinical trial, aiming to enter the later stage of clinical trials

Major global pharmaceutical companies have accomplished successful marketing of bispecific antibodies.

 

Now, the Korean biopharmaceutical industry is also joining this challenge.

 

Current bispecific antibodies include Roche’s Lunsumio and Columvi, Abbvie’s Epkinly, and Janssen’s Tecvayli.

 

Korean companies are planning to evaluate the possibility of developing bispecific antibodies in an area of immunotherapy.

 

According to industry sources on the 26th, Hanmi Pharm, ABL Bio, and ImmuneOncia joined the race to develop bispecific antibodies.

 

Bispecific antibodies are known to have clinical advantages as they have additional specific antigen-binding sites compared to monoclonal antibodies.

 

Korean biopharmaceutical companies have started developing anticancer therapy with bispecific antibodies.

Hanmi Pharm’s immunotherapy candidate product BH3120 has recently entered Phase 1 clinical trials.

 

BH3120 simultaneously targets 4-1BB and PD-L1.

 

PD-L1 is a target that immunotherapies, such as Keytruda and Opdivo, have demonstrated effectiveness.

 

Hanmi plans to expand the antibody’s efficacy by also targeting 4-1BB protein.

 

Hanmi’s bispecific antibody platform technology, Pentambody, was applied to developing BH3120.

 

Pentambody is a next generation bispecific antibody platform technology that stimulates immune cells while attacking target cancer cells simultaneously.

 

BH3120 is designed to activate 4-1BB specifically in the immune cells near PD-L1-expressing cancer cells.

 

This design minimizes toxicity while demonstrating anti-cancer efficacy in preventing late recurrence.

 

ABL Bio has the most bispecific antibodies of any pharmaceutical companies in Korea.

 

ABL Bio has more than seven pipelines including ABL001(VEGFxDLL4), ABL111(Claudin18.2x4-1BB), and ABL503(PD-L1x4-1BB).

 

ABL Bio is also developing ABL001 jointly with Handok.

 

Handok has entered into a licensing agreement with ABL Bio, securing the rights of the drug in Korea and the company has been focusing on biliary tract cancer since February 2021 and conducting Korean Phase 2 clinical trial of ABL001(HDB001A).

 

Handok’s Korean Phase 2 clinical trial, which enrolled patients with biliary tract cancer, demonstrated drug’s efficacy.

 

Therefore, Handok has established a foundation for expanding into multinational clinical studies.

 

In the clinical trial, ABL001 was administered in combination with Paclitaxel to patients who had received their first or second systemic anticancer therapies.

 

The combination therapy demonstrated an objective response rate (ORR) of 37.5%.

 

The median overall survival (OS) was reported to be 12.5 months, with an estimated median duration of response rate (DOR) of 9.4 months.

 

The company is planning to enter later stage clinical trials.

 

ABL Bio announced the interim analysis of Phase 3 for ABL111 last year.

 

The company aims to secure indications for solid cancer by simultaneously targeting Claudin18.2 and 4-1BB.

 

ABL111 did not show any serious adeverse reactions of greater than level4, with an index of 4-1BB-specific toxicity side-effects, according to the company.

 

Additionally, ABL503 is a cancer immunotherapy that simultaneously targets PD-1 and 4-1BB, similar to Hanmi’s BH3120.

 

According to the Phase 1 clinical trial result, one instance of complete response (CR) and three instances of partial remission (PR) were confirmed in ovarian cancer patients administered with ABL503.

 

The Phase 1 clinical trial of ABL503 is currently being conducted at six institutions in the United States and three institutions domestically, focusing on dose escalation and expansion parts.

 

Once the optimal dosage is determined, the plan involves identifying the most suitable target among solid tumors.

 

ImmuneOncia’s IMC-201 is an independently developed bispecific antibody utilizing CD47 and PD-L1.

 

In the preclinical study, IMC-201 binds strongly to solid cancer cells or blood cancer cells expressing CD47/PD-L1 and selectively binds to cancer cells even when cancer cells and red blood cells are co-cultured.

 

In addition, IMC-201 exhibited higher macrophage-dependent phagocytosis than monoclonal antibody IMC-002.

 

Particularly in a mouse tumor model of triple-negative breast cancer, IMC-201 showed more substantial tumor suppression than the combination of monoclonal antibodies IMC-002 and IMC-001.

 

ImmuneOncia is developing cancer immunotherapy candidate IMC-002.

 

IMC-002 blocks the signal between CD47 on cancer cells and macrophages.

 

The result of IMC-002 administration to 12 patients demonstrated no drug toxicity in each dose.

 

6 out of 12 patients showed stable disease (SD).

 

The company will determine the recommended dose based on Phase 1 clinical study results.