HONG KONG – Denovo Biopharma LLC, a cross-border biotech registered in San Diego and Hangzhou, China, has been granted IND approval by Chinese regulators to conduct international multicenter clinical trials for its neuroscience drug, DB-103 (pomaglumetad). If successful, DB-103 could prove a heavyweight product in the schizophrenia space.

HONG KONG – Denovo Biopharma LLC, a cross-border biotech registered in San Diego and Hangzhou, China, has been granted IND approval by Chinese regulators to conduct international multicenter clinical trials for its neuroscience drug, DB-103 (pomaglumetad). If successful, DB-103 could prove a heavyweight product in the schizophrenia space.

DB-103 is a first-in-class psychiatric drug designed to selectively act on the glutamic acid mGlu2/3 receptor, setting it apart from current drugs used in the clinical treatment of psychosis, which mainly focus on dopamine D2 receptors in the central nervous system (CNS).

The mGlu2/3 receptor agonist has no cross-reaction with other receptors in the CNS, so it can avoid some of the usual side effects such as weight gain. DB-103 also produces less serious extrapyramidal symptoms.

"We plan to run the trials at multinational sites," Wen Luo, CEO of Denovo, told BioWorld Asia. "China will be included for sure. As for now, we are still evaluating other countries such as the U.S. and in Asia Pacific.

"If this proof of concept runs successfully, we will need to conduct two more phase III trials," he added.

"Eventually, we plan to file NDA submissions in China and the U.S. simultaneously, and in countries that might be eligible," though Luo said a specific timeline is hard to foresee so early in the process.

The multicenter study testing DB-103 will be the second global trial Denovo has initiated this year. In April, the company dosed the first patient in China in a phase III trial of DB-102 (enzastaurin) to treat diffuse large B-cell lymphoma. (See BioWorld, April 17, 2018.)

Luo also noted that the China IND approval arrived much faster than he expected. "We were pleasantly surprised to get this China IND approval that soon. This was unthinkable a few years ago. China approval used to take much longer time," he said.

While not revealing how many days it took the company to obtain the green light, he hinted at the Chinese regulators' efficiency. For the antitumor drug DB-102, China IND approval came around the same time as the U.S. approval.

"This is also because DB-103 is a class I new drug, hence an expedited review. It is still very rare for China to develop a first-in-class drug, so DB-103 carries significance," Luo said.

Turning failure to success

The psychiatric drug was first developed by Eli Lilly and Co. to treat schizophrenia. But, in 2012, the pharma giant stopped development after the drug failed to meet the primary endpoint in the intent-to-treat population in the second phase III study.

Despite that, Denovo has pointed to the drug's promise. "Predefined subpopulation analysis and post-hoc analysis across multiple studies identified a meaningful subset of patients who showed significantly improved outcomes," the company said in March 2015.

In the same month, Denovo inked a deal with Indianapolis-based Lilly to obtain the global rights to develop, manufacture and commercialize the late-stage compound.

"It was a bit of an effort to convince Lilly that it would be a win-win to out-license the drug to us. Otherwise the compound would just be shelved and collecting dust. We do the work to bring it back to the market, and Lilly can get the milestone and royalty payment," Luo said.

According to Luo, Denovo's strategy is to acquire failed drugs and the clinical samples of the patients involved in the trial. The biotech firm then uses its biomarker platform or other strategic analysis tools to find patients who might benefit from the drug that would otherwise fail.

"We typically buy the whole program with global rights. We run the new trials ourselves to bring the drug back to the market," Luo noted.

"Lilly had conducted more than 30 clinical trials on this compound, including phase I, II and phase III studies. Data from 3,500 subjects show that DB-103 is very safe," he added.

Under the agreement, Lilly has priority repurchase rights. If the U.S. pharma repurchases DB-103, Denovo will receive a success fee, back milestone payments and future sales royalties.

But Luo said Lilly would face a high price tag to buy it back, as he contended that DB-103 has the potential to be a blockbuster given the sheer patient population and market size.

"Schizophrenia affects 1 percent of the total population. When there are 1.4 billion people in China, this can mean 10 million Chinese patients," he said.

"One percent is a huge number, globally speaking. The market is bigger than that of many of the oncology drugs."

So far, there is no competitor for DB-103 given its unique mechanism of action. Profits from the drug could be enormous, though Luo noted Chinese patients are unlikely to suffer a skyrocketing price.

Denovo's approach to obtaining the global rights makes pricing more flexible. When other biotech companies only get the China rights, they will need to capitalize on them, he explained.

"The contribution from the China market is still limited at the moment, representing around 5 percent or less of the global market for a typical blockbuster drug," he said. "So we do not need to rely on the China market that much, which means we can make this drug more affordable for patients in China."

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