Therapex has entered clinical trials to develop a fourth-generation
drug for Epidermal Growth Factor Receptor (EGFR) mutant lung cancer. In the
absence of appropriate treatment following resistance to Tagrisso (Osimertinib),
pharmaceutical companies worldwide are focusing efforts on developing fourth-generation
lung cancer drugs.
Therapex will employ a development strategy to enhance drug
efficacy by targeting various genetic mutations that develop after Tagrisso
administration. Additionally, the plan is to demonstrate efficacy on brain
metastases in clinical trials based on preclinical data showing high
blood-brain barrier (BBB) permeability.
◇ FDA approved IND for Phase
1/2 Clinical Trial...to conduct global clinical trials for over 100 subjects in
the U.S. and Korea
Therapex has received the U.S. Food and Drug Administration
(FDA)'s approval of the Investigational New Drug (IND) Application for a Phase
1/2 Clinical Trial with the EGFR mutant non-small cell lung cancer drug
pipeline “TRX-221”. Approximately 100 subjects will be enrolled in this study.
The objective is to evaluate partial efficacy, along with safety and
tolerability, in Phase 1, and then move to overall efficacy in Phase 2.
As soon as Phase 1/2 is approved, clinical trials will be
conducted in Korea, Australia, and Taiwan, as well as the United States. The
first patient enrollment in the Phase 1/2 Clinical Trial is planned for early
next year.
Before entering clinical trials, Therapex focused on securing
data on efficacy, as well as safety, in preclinical research. One of the major
results of the study is the reduction in off-target toxicity.
In addition, the results indicate that no weight loss was
observed even with an increased dose. The study also employed a strategy to
improve clinical predictability using the Patient-Derived Orthotopic Xenograft
(PDOX) models. The PDOX model is known as the animal model that best predicts
actual patient outcomes by transplanting tissue from actual cancer patients
into mice with human immune systems.
Therapex used the PODX model to conduct preclinical research of
TRX-221. The results of this research were announced at the American
Association for Cancer Research (AACR) Meeting 2023 and the European Society
for Medical Oncology (ESMO) 2023 conferences this year. In addition, animal
models of brain tumors have demonstrated the drug's permeability across the
blood-brain barrier.
"The Patient-Derived Xenograft (PDX) and PDOX models showed
sufficient efficacy in carcinoma remission," said a representative of
Therapex. "The significance lies in demonstrating remission efficacy
compared to competitor pipelines, which only showed significant inhibition of
carcinoma growth."
◇ Aiming for Market Expansion
with 'Broad Spectrum': Targeting Diverse Tagrisso-Resistant Variants
The development of TRX-221 will employ a strategy to increase
efficacy by targeting not only C797S mutations, which arise after administering
third-generation EGFR lung cancer drugs, but also a broad spectrum of mutations
such as Del19, L858R, and T790M.
Currently, the fourth-generation of EGFR mutant lung cancer drugs
primarily target C797S and are being developed with efficacy comparable to that
of third-generation drugs such as Tagrisso. Some of these third-generation
drugs do not show efficacy for mutations such as T790M.
Therefore, the efficacy against triple mutations
(del19/T790M/C797S, L858R/T790MC797S) may be limited in some of the fourth-generation
drug pipelines, as they do not inhibit them. The key is whether the fourth-generation
drugs can address a broad spectrum of mutations.
Therapex plans to develop a second-line or third-line treatment
first for Tagrisso-resistant patients. Additionally, leveraging the
broad-spectrum targeting characteristics of the pipeline, clinical treatments
as first-line therapy will be developed as another future strategy.
"The mutations that may arise following the prescription of
Tagrisso as a first-line or second-line therapy can be diverse," stated
the Therapex representative. "Our development strategy aims to enhance
Tagrisso's efficacy by targeting most mutations, including C797S, at any stage
of Tagrisso administration."