BEIJING – Cross-border biotech Denovo Biopharma LLC, registered in San Diego and Hangzhou, China, is planning for a pre-revenue listing on Shanghai's high-tech board (STAR) to support a key trial.

Denovo aims to use the proceeds to fund a global phase III study in diffuse large B-cell lymphoma (DLBCL) testing DB-102 (enzastaurin), an orally available small molecule serine/threonine kinase inhibitor of the PKC beta and AKT pathways. It is the most advanced asset in Denovo's pipeline, which comprises four potentially first-in-class drug candidates.

"For DLBCL, the first indication that DB-102 is being developed to treat, our patient enrollment rate has reached 70 percent," Denovo's chief financial officer, Carrie Chen, told BioWorld Asia. "We expect to submit an NDA in both China and the U.S. by the second or third quarter of 2021."

In 2017, Denovo closed a series B financing round to snatch $43 million to support that global phase III trial, and the first patient was dosed in China last year. As the company gets closer to commercialization, Chen said timing is ripe for the biotech to go public.

"We have first-in-class drug candidates and own the global rights, unlike other players that focus on developing 'me-too' drugs and only have the China rights. And speaking from the perspective of our R&D progress, we are quite far ahead given the enrollment rate of our global phase III trial," she explained.

Denovo is undergoing share reform to seek listing as a pre-revenue biotech company on the STAR board. Chen said the pre-IPO financing round "is going well," and the company can file for a listing soon.

"We are a Chinese biotech and now China provides very favorable policies to support innovative companies like us. The securities regulators also want to keep us in China," said Chen, when asked why Denovo eyes the STAR but not the Hong Kong Stock Exchange (HKEX).

The phase III trial, known as ENGINE, is a global, randomized, double-blind study evaluating the efficacy of DB-102 in combination with R-CHOP vs. R-CHOP alone in DLBCL patients with or without the biomarker DGM1. R-CHOP is the monoclonal antibody rituximab with chemo drugs cyclophosphamide, doxorubicin, vincristine and prednisone, which remains the standard of care for DLBCL.

The study aims to enroll 235 patients. The primary outcome measure is overall survival in patients with DGM1. The number of patients is relatively small for a phase III study, but the biomarker approach for selecting responsive patients is expected to generate statistically significant results.

Enzastaurin was originally developed by Eli Lilly and Co. The Indianapolis-based firm spent more than 15 years and ran 60-plus clinical trials. But enzastaurin has failed already twice before, missing efficacy targets in both DLBCL and in glioblastoma in phase III trials.

Denovo obtained the global rights for DLBCL and glioblastoma from Lilly. The two phase III trials run by Lilly and numerous other studies generated a vast amount of patient data, which Denovo has mined using its biomarker platform and algorithms to discover de novo genomic biomarkers. Eventually Denovo spent a year to discover a novel biomarker and patented it as DGM1. (See BioWorld, April 18, 2018.)

The biomarker population that responds to the drug represents the majority of DLBCL patients, and Denovo said it believes DB-102 is a potential blockbuster.

As for the second indication, glioblastoma, Denovo won FDA approval in September to initiate a phase IIb study in patients with newly diagnosed glioblastoma in combination with radiation and temozolomide.

Denovo said since DGM1 is a germline biomarker, it also predicts a survival benefit in patients with glioblastoma treated with DB-102 plus temozolomide. The trial is expected to enroll around 200 patients.

"Glioblastoma remains one of the toughest cancers to treat, and numerous attempts have failed, including anti-PD-1 antibodies," said Lei Zhang, Denovo's chief medical officer. "DB-102 treatment guided by the novel DGM1 biomarker could potentially provide a breakthrough for this severely unmet medical need."

Denovo is known for acquiring distressed assets to redevelop them. It applies biomarker approaches to re-evaluate drugs that have failed in broad patient populations.

From Lilly it also acquired the rights to DB-103 (pomaglumetad), a first-in-class drug designed to selectively act on the glutamic acid mGlu2/3 receptor to treat schizophrenia. It is currently in phase II testing.

The biotech has two more first-in-class assets, DB-104 (liafensine) for depression, originated by Albany Molecular Research and Bristol-Myers Squibb Co., as well as DB-105 for Alzheimer's disease that was discovered by Orion Corp. and acquired in June. Denovo has the global R&D, manufacturing and marketing rights to both of them. (See BioWorld, June 20, 2019.)

And there will be more this year.

"We expect to add a new oncology asset, DB-106, to our pipeline by the end of this year," Chen told BioWorld Asia, but not revealing details yet.

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