Korean and global pharmas in race for lung cancer drugs

of 4th-generation

J INTS BIO, clinical phase 1/2a…Bridge Biotherapeutics enters a clinical trial

Overseas, Black Diamond Therapeutics leads the clinical race

4th-generation targeted therapies must surpass ADC clinical data to seek the possibility of commercialization

Pharmaceutical and biotechnology companies in South Korea are conducting clinical trials to overcome drug resistance in conventional non-small cell lung cancer (NSCLC) therapy.

 

These companies are developing 4th-generation lung cancer treatments that have proven effective in patients with drug resistance after the use of 1st-to-3rd-generation targeted therapies.

 

Conventional EGFR-positive NSCLC therapies are categorized into 1st-generation AstraZeneca’s Iressa (gefitinib) and Roche’s Tarceva (erlotinib), 2nd-generation Boehringer Ingelheim’s Giotrif and Pfizer’s Vizimpro (dacomitinib), and 3rd-generation Yuhan Pharmaceutical’s Leclaza (lazertinib) and AstraZeneca’s Tagrisso (osimertinib).

 

However, drug resistance can still occur when using targeted therapies with proven effectiveness.

 

The C797S mutation is the most common mutation in EGFR-positive targeted therapies.

 

Treatment options following the targeted therapies are limited.

 

Patients with resistance to targeted therapies have the option of using anticancer chemotherapy, docetaxel, or cancer immunotherapy.

 

However, these drugs do not significantly improve response rates.

 

Latecomer companies target a C797S mutation that causes resistance after the conventional 1st-to-3rd-generation targeted therapies, aiming to seek commercialization opportunities.

 

The analysis is that these drugs compete against antibody-drug conjugates (ADC), which have proven effective in patients resistant to targeted therapies, for commercialization.

 

The K-Bio industry is conducting clinical trials targeting C797S mutation According to industry sources on April 6, domestic biotech venture J INTS BIO presented clinical phase 1/2 results on its 4th-generation EGFR-positive candidate JIN-A02.

 

Byoung Chul Cho (Director of the Lung Cancer Center at Yonsei Cancer Hospital), who is also in charge of Leclaza and Rybrevant, leads the clinical stage of JIN-A02.

 

JIN-A02, a 4th-generation EGFR tyrosine kinase inhibitor (TKI), has an underlying mechanism of action that selectively binds to C797S, which causes resistance to 3rd-generation NSCLC treatment.

 

In the clinical study, JIN-A02 confirmed a partial response (PR) in one patient and stable disease (SD).

 

J INTS BIO explained that among 4th-generation EGFR-TKI treatments, it is the first instance of PR in patients with the C797S mutation.

 

Bridge Biotherapeutics is developing BBT-207, a 4th-generation EGFR-positive lung cancer treatment.

 

A phase 1/2 trial of BBT-207 is currently being conducted, enrolling 90 patients with EFGR-positive NSCLC in South Korea and the United States.

 

Bridge Biotherapeutics plans to understand data on different mutations in patients acquired through liquid biopsy.

 

In a preclinical trial, BBT-207 demonstrated anti-tumor effectiveness in various EGFR mutations, including the C797S mutation.

 

Therapex has received approval from the Ministry of Food and Drug Safety (MFDS) for a phase 1/2 TRX-221 trial last month.

 

Therapex plans to determine the recommended dose in Phase 1 and assess effectiveness in Phase 2a.

 

The company aims to obtain approval for the indication in advanced NSCLC with EGFR C797S mutation.

 

Previously, Therapex demonstrated the drug’s dose-dependent anticancer efficacy and blood-brain barrier (BBB) permeability in a Tagrisso-resistant brain tumor mouse model.

 

Voronoi has obtained approval for a phase 1 trial in South Korea and is conducting the clinical trial.

 

Voronoi also targets EGFR C797S.

 

Through this phase 1 trial, the company plans to evaluate the drug’s effectiveness against the C797S-resistant mechanism of action.

 

HK inno.N is conducting research on IN-119873, a 4th-generation targeted anticancer treatment, for patients who have shown resistance in the first-line treatment of NSCLC or have an L858R mutation.

 

Unlike conventional treatments that target the binding site of adenosine triphosphate (ATP), an energy source of cancer cells, IN-119873 targets the allosteric binding site (one of the protein binding sites) of the EGFR, providing a significant advantage.

 

Korean and overseas companies are developing fourth-generation EGFR-positive targeted lung cancer treatments.

 

For overseas pharmaceutical companies, Black Diamond Therapeutics leads the clinical race…Will it surpass ADC Overseas pharmaceutical companies, as well as Korean biotechnology companies, are actively conducting clinical trials on 4th-generation lung cancer treatments.

 

Black Diamond Therapeutics confirmed the highest number of partial responses (PR) in their phase 1/2 clinical trial.

 

They are repurposing their existing brain tumor treatment, BDTX-1535, as a 4th-generation lung cancer targeted therapy.

 

In a clinical trial targeting NSCLC patients with acquired resistance to targeted therapy, Black Diamond Therapeutics's 4th-generation EGFR-TKI treatment, BDTX-1535, yielded results of five patients with partial response (PR) and six patients with stable disease (SD) out of a total of twelve.

 

In contrast, the U.S.-based Blueprint Medicines faces difficulties in drug development as it failed to confirm efficacy in Phase 1 clinical trials.

 

The company faced setbacks with its 4th-generation targeted therapy candidate, BLU-945 monotherapy.

 

However, the company is currently exploring the possibility of commercializing it as a combination therapy with Tagrisso.

 

Blueprint Medicines plans to target exon 21 L858R mutations rather than the C797S mutation in Tagrisso-resistant patients.

 

However, the commercialization of these targeted therapies faces a challenge in surpassing ADC clinical results.

 

Currently, Daiichi Sankyo and MSD are jointly developing an ADC that has shown effectiveness in Tagrisso-resistant patients, and their data are being disclosed.

 

Daiichi Sankyo and MSD’s Patritumab deruxtecan, which targets human epidermal growth factor receptor 3 (HER3), has shown effectiveness in EGFR-TKI patients compared to platinum-based chemotherapy in the phase 2 HERTHENA-Lung01 study.

 

In the clinical trial, patritumab demonstrated complete responses (CR) and confirmed 66 partial responses (PR).

 

The objective response rate (ORR) was observed at 29.8%.

 

Currently, this treatment is designated as a priority review drug by the U.S.

 

Food and Drug Administration (FDA), with approval expected to be finalized in June of this year.