HONG KONG – New results from a study of South Korean company Qurient Co. Ltd.'s orally available antibiotic, telacebec, suggest it is moving closer to offering a new therapeutic option for people with multidrug-resistant tuberculosis (MDR-TB). The company's phase IIa trial focused on early bactericidal activity (EBA) in MDR-TB, a form of the infection that does not respond to at least two of the most powerful anti-TB drugs, isoniazid and rifampicin.

Should it succeed, telacebec would take its place in the market alongside Janssen Research & Development LLC's bedaquiline and Otsuka Pharmaceutical Co. Ltd.'s delamanid, the two drugs most commonly used for the treatment of MDR-TB and extensively drug-resistant TB (XDR-TB).

Telacebec, also known as Q-203, is a selective inhibitor with high specificity for the cytochrome bc1 complex of Mycobacterium tuberculosis. The complex is a critical component of the electron transport chain and its inhibition disrupts the bacterium's ability to generate energy.

Qurient's EBA trial, run in South Africa, assessed the pharmacokinetics, safety and activity of telacebec in three different dose strengths – 100 mg, 200 mg and 300 mg – when used to treat adults suffering from pulmonary TB. According to the company, telacebec met the primary objective of rate of change in the time to positivity in sputum over the first 14 days.

"It usually takes more than two months to diagnose kinds of drug-resistant tuberculosis, and different drugs are prescribed for each disease," Qurient CEO Kiyean Nam told BioWorld. "Based on our research, we expect that telacebec will be effective on not just MDR-TB but also XDR-TB and totally drug-resistant tuberculosis."

The company in-licensed telacebec from the Pasteur Institute in South Korea. The drug has so far secured both FDA orphan status and a fast track designation.

According to the World Health Organization (WHO), the bacteria that causes TB can develop resistance to the antimicrobial drugs used to cure the disease. The mismanagement of treatment has led to the spread of multidrug resistance.

In 2016, an estimated 490,000 people worldwide developed MDR-TB, and an additional 110,000 people with rifampicin-resistant TB (MDR/RR-TB) required treatment.

The countries with the largest numbers of MDR/RR-TB cases, accounting for 47% of the global total, were China, India and Russia, with roughly 6.2% of those cases being XDR-TB.

Telacebec may also have potential to treat Buruli ulcer (Mycobacterium ulcerans), according to research results published on the December 2018 edition of Nature Communications, Nam said.

Besides telacebec, Qurient has developed four other drugs for cancer and inflammation. Q-702 is a triple (Axl/Mer/CSF1R) inhibitor for immune-oncology and drug-resistant non-small-cell lung cancer. The drug has been licensed from Max Planck Innovation and the Lead Discovery Center in Germany.

Axl and Mer receptor tyrosine kinase may play important roles in multiple cancer indications. Axl has been known to promote epithelial-to-mesenchymal transition leading to drug and immune resistant tumors. And, according Qurient, Axl and Mer's roles in inactivation of innate immunity in cancer and enveloped viral infection have been reported.

Another Qurient candidate, Q-301 (zileuton) is the first topical leukotriene inhibitor being tested against atopic dermatitis (AD). It is currently in phase IIb development.

The most commonly used topical treatment for AD is corticosteroids, which can carry serious adverse effects prohibiting continuous use. Despite the recent approval of non-steroid topical agents for AD, the development of therapeutic agents with a novel mechanism of action is still needed.

Q-301 achieved proof of concept in a phase IIa study carried out with 60 moderate to severe AD patients based on Investigator's Global Assessment (IGA) score. In the study, about 30% of Q-301-treated patients showed clear to almost clear (IGA grade 0 or 1, respectively) with at least two degrees of improvement.

Q-301 is currently under phase IIb study with 240 mild to moderate AD patients in the U.S. based on IGA and EASI score.

In addition, the biotech company is developing candidates for selective CDK7 inhibitor for the treatment of solid tumors and oral 5LO inhibitor for the treatment of asthma.

Founded in 2008, Qurient has a staff of about 20 who manage their own projects, incorporating outside medical expertise. The company maintains its small size to ensure it can move quickly to develop innovative new drugs, Nam said.

Qurient's stock price on the KOSDAQ index in South Korea (KRX:115180) fell slightly from KRW22,650 (US$19.16) to KRW22,300 (US$18.85) on June 3.