K-Bios seek drugs to be used in combination with ADCs

Seeks candidates to partner with Enhertu

Confirms potential in combination with Enhertu, which demonstrated an effect in various solid cancers

Gi innovation, AbClon changes trial protocol and seeks use in combination with immuno-oncology and targeted antitumor drugs

The domestic pharmaceutical and bio-industry are changing clinical trial protocols and confirming the possibility of their use in combination therapy with antibody-drug conjugates (ADCs).

 

In particular, a growing number of companies are trying to use their drugs in combination with Enterhu, which has shown an effect across solid cancers For example, GI Innovation and AbClon are aiming to maximize the effectiveness of their existing immuno-oncology and targeted anti-cancer drugs by using their drug in combination with Enhertu.

 

In particular, they expect to show benefits in terms of side effects by combining a reduced dose of Enhertu with their respective new drug candidates that are under development.

 

Change in clinical trial protocol…expects to double their drug’s effect by adding Enhertu

Daiichi Sankyo and AstraZeneca

According to industry sources on the 24th, GK Innovation and AbClon have been evaluating the possibility of combining their respective drug candidates with Enhertu.

 

Enhertu is a new antibody-drug conjugate anticancer drug that was codeveloped by Daiichi Sankyo and AstraZeneca.

 

It is a next-generation ADC that combines a monoclonal antibody with the same structure as trastuzumab, which binds to a specific target receptor overexpressed on the surface of cancer cells, and a topoisomerase I inhibitor payload with a tumor-selective cleavable linker, which is a novel and highly potent mechanism of action.

 

ADCs are anticancer drugs manufactured by linking an antibody that binds to a specific target antigen on the surface of cancer cells with a drug that has cell-killing (cytotoxic) properties.

 

ADCs act selectively on cancer cells, by using the selectivity of antibodies to their targets and the killing activity of drugs to increase therapeutic efficacy while minimizing side effects.

 

While the first-generation ADC, Roche’s Kadcyla, was only approved for breast cancer, second-generation ADCs such as Enhertu have been succeeding in securing a variety of indications.

 

Currently, Enhertu is approved for HER2-positive gastric cancer, breast cancer, and non-small cell lung cancer.

 

The domestic pharmaceutical and biotech industry has also taken note of the effectiveness of Enhertu and is trying to change their clinical trials to attempt its use as a combination therapy.

 

GI Innovation recently changed a Phase I/II clinical trial for its immuno-oncology drug candidate 'GI-102' in the U.S.

 

to a study to confirm its efficacy in combination with Enhertu.

 

GI-102’s pipeline targets tumors and immune cells by targeting CD80 and interleukin (IL)-2 and has been engineered to have lower alpha receptor binding compared to GI-101A.

 

High alpha receptor binding is known to increase regulatory T cells, which reduces the anti-cancer effects.

 

GI-102 is being developed as both intravenous (IV) and subcutaneous (SC) formulations.

 

GI-102 has also shown promise as monotherapy in trials.

 

Recently, the company's Phase I/IIa data showed an objective response rate (ORR) of 43% when GI-102 was administered to patients with melanoma.

 

In addition, lymphocyte proliferation was enhanced by GI-102 treatment, with no serious drug toxicity observed.

 

Therefore, GI Innovation expects that the combination of GI-102 and Enhertu will bring greater effect.

 

The company believes that the combination of GI-102 with a reduced dose of Enhertu can reduce side effects such as interstitial lung disease (ILD) that occur with Enhertu alone.

 

AbClon recently announced that a new IND for its lead drug candidate, AC1-01, has been approved in China.

 

AC-101 is an antibody-drug developed by AbClon that targets HER2 mutations.

 

Its technology was licensed out to Henlius in China in 2016.

 

The new trial will test the effectiveness of AC-101 in combination with Herceptin or Enhertu, both of which are used in breast cancer.

 

With this change, AbClon plans to test its potential in gastric cancer and other solid tumors.

 

Previously, AC-101’s efficacy was validated in combination with Herceptin.

 

In patients with HER2-positive gastric cancer, the ORR, which signifies the reduction in tumor size measured at 72 weeks post-dose, was 41.2% in the low-dose arm, 16.7% in the high-dose arm, and 5.6% in the control arm.

 

Based on such results, the company expects the addition of Enhertu to extend the benefits of AC-101 across HER2-positive solid tumors.

 

Voronoi is also open to the possibility of combining its drug with Enhertu.

 

The company is developing VRN10, a HER2-positive targeted therapy.

 

VRN10 entered Phase I clinical trials last month.

 

The Phase I trial of VRN10 is being conducted at 5 sites in Korea and Australia in approximately 70 patients with solid tumors, including HER2-positive breast cancer.

 

In preclinical studies, VRN10 was found to be highly active against Enhertu-resistant cells.

 

Voronoi believes that its selectivity for the HER2 biomarker may improve side effects such as diarrhea and dermatitis, and its brain penetration is superior to existing therapies.

 

Voronoi expects the combination of VRN10 and the HER2 ADC to bring synergy.