SHANGHAI – Shanghai-based Ark Biosciences Inc., a virtual biotech, and the California Institute of Biomedical Research (Calibr), of La Jolla, an affiliate of The Scripps Research Institute (TSRI), one of the world's largest private biomedical research institutes, have partnered to develop preclinical assets for chronic obstructive pulmonary disease (COPD).
Both sides have equal ownership of the global rights and will work in partnership to co-develop the programs. Ark will take the lead on development, while the U.S. team will help with further compound optimization as required.
"We are excited to collaborate with Calibr to develop novel and potentially first-in-class therapeutics for the treatment of COPD, a progressive lung disease with no cure. Our collaboration is based on the groundbreaking discovery at Calibr/TSRI recently published in Science." said Jim Wu, Ark's CEO.
The discovery in question is decarboxylative borylation, a new chemical method that replaces carboxylate with a boric acid moiety in drug molecules. Scientists at Scripps/Calibr demonstrated kinetically, by forming a reversible covalent bond, drug molecules can stay on target much longer to exert pharmacological effects.
They have used that technology to modify human neutrophil elastase (HNE) inhibitors that have been studied in late-stage clinical trials, seeking to make them more potent and more druggable. "Lack of lung exposure and unfavorable inhibition kinetics are certainly some reasons for lack of efficacy in HNE inhibitors," Wu added. He declined to say which HNE inhibitors researchers are working on.
HNE is a highly active serine protease that plays a pivotal role in COPD by breaking down mechanically important structures of the body's cellular matrix and proteins of foreign origin.
According to the Calibr/TSRI authors of the Science paper, while "five generations of HNE inhibitors have been evaluated clinically in multiple inflammatory lung diseases (e.g., cystic fibrosis, emphysema, and bronchiectasis), none have been overwhelmingly efficacious in humans to make a significant impact in these conditions."
Given China's poor air quality and large number of smokers, it is no surprise that the country has serious unmet medical needs in the area of respiratory disease. COPD is the second leading cause of morbidity and mortality in China, where the overall prevalence was 8.2 percent in 2004 (the last time a landmark study was completed).
However, few biotechs in China are tackling respiratory diseases.
"If you look at other Chinese biotech companies, most of them work on immunotherapy, immune-oncology [but] few focus on COPD and respiratory diseases; most think of respiratory disease as very challenging to come up with efficacious therapy, but I think we understand the science very well," said Wu.
Ark's experience in respiratory diseases comes from its lead program, AK-0529, for the treatment of respiratory syncytial virus (RSV), a common virus that can be deadly in premature infants, children and the elderly by infecting the lungs and respiratory tract. (See BioWorld Today, June 20, 2014.)
AK-0529 is currently in a phase II randomized, double-blind, placebo-controlled global study, across eight countries, enrolling 80 hospitalized infants. Study results are expected by the middle of 2018.
Wu first worked on AK-0529 as a senior research executive with Roche China, a unit of Roche Holding AG, of Basel, Switzerland. When Roche decided to shelve the project for strategic reasons, Wu convinced his former employer to license it to him to continue its development, allowing him to set up his own shop.
Ark's AK-0529 is designed to work by inhibiting RSV replication, blocking viral entry and syncytium formation.
Ark's experience and network in respiratory diseases is what makes the company a strong partner, Wu said. Although it is small, with 25 people, the firm has offices in Suzhou, Shanghai, Switzerland and Australia.
"We know respiratory diseases well. We know the KOLs and the hospitals. We know how to formulate a drug specifically for respiratory diseases to achieve that efficacy," he said.
He also points to other advantages of working with a committed biotech, especially in China.
"If you look at the biotech landscape, China is emerging as a major force in drug discovery and development," Wu said. "If you look inside China, our company is one of the few working on first-in-class or even first-in-disease programs. If an academic institute licenses a preclinical drug to a big pharma, the development process could be slow and inefficient; it might even get put on the shelf, but working with a small and dynamic biotech company like Ark makes a lot of sense."
The deal with Ark is Calibr's second in China this year. In April, it inked a collaborative agreement with Hitgen Ltd., of Chengdu, to focus on oncology, regenerative medicine and virology. Hitgen's technology platform will be used to identify small-molecule targets while Calibr will provide target materials and expertise.