HONG KONG – Hangzhou, China-based Adlai Nortye Biopharma Co. Ltd. said Tuesday it partnered with Novartis AG to obtain the worldwide rights to BKM-120 (buparlisib), a selective PI3K inhibitor, to treat head and neck cancer, adding one more lead product to the Chinese company's oncology pipeline.

The licensing agreement with Novartis arrived at a good time – Adlai Nortye just completed a series B financing last month of $53 million for advancing its cancer drug candidates that are in the clinical.

"We currently have three in-licensing lead products in clinical development," Dexter Fong, chief financial officer at Adlai Nortye, told BioWorld. "They are Reolysin, AN-0025 and BKM-120.

"Other than that, part of the proceeds will be used for setting up a laboratory in Boston that is slated to open on Aug. 8 for research in translational medicine, as well as an antibody laboratory and a clinical team in New Jersey," Fong added.

The biopharma firm focuses on the development of innovative drugs in immuno-oncology, with a goal to turn cancer into a chronic disease.

Developed by Novartis, BKM-120 is an oral pan-PI3K inhibitor that targets all class 1 PI3K isoforms and is active in both hematologic malignancies and solid tumors. The drug has shown promising efficacy in combination with paclitaxel in head and neck squamous cell carcinoma. It is currently in phase III trials.

"BKM-120 has been granted fast track designation by the U.S. FDA. Besides head and neck cancer, it may also be able to treat PIK3CA mutations in solid tumor. We plan to launch it by the end of 2021, or early 2022," said Fong.

Another lead product is Reolysin, an intravenously delivered immuno-oncolytic virus to treat solid tumors, including breast cancer. It will enter global multicenter phase III trials by the end of this year.

In November, Adlai Nortye obtained the rights to Reolysin from Canada-based Oncolytics Biotech Inc. to develop and commercialize it in greater China, Singapore and South Korea. For the phase III trial, Adlai Nortye will recruit 50 to 70 patients in China.

Turning point

The partnership with Oncolytics Biotech was a turning point for Adlai Nortye.

"It immediately makes Adlai Nortye a late-stage biotechnology company and Reolysin itself becomes our lead product," said Adlai Nortye's CEO, Carsten Lu.

The Chinese firm said it believes Reolysin, the second-generation oncolytic virus, holds vast potential as it features a few advantages in addition to its low toxicity.

"Reolysin activates the innate and adaptive immune systems to turn 'cold' tumors 'hot'," Fong explained. "It is superior to the first-generation oncolytic virus because it does not need direct injection into the tumors. It is injected intravenously, so its efficacy will not be limited by the size and location of the tumor. Also, it does not require genetic modification."

"Reolysin was granted fast track designation by the U.S. FDA. We expect to launch it in China by the end of 2021, or early 2022," he added.

The third lead product at Adlai Nortye is AN-0025, an investigational, oral EP4 antagonist, also for treating solid tumors. It is now in global phase Ib combination studies with radiotherapy and chemoradiotherapy.

In January, Adlai Nortye obtained from Japanese pharma firm Eisai Co. Ltd. the rights to E-7046 – now known as AN-0025 under Adlai Nortye. The company may develop, manufacture and commercialize AN-0025 worldwide, except in Japan and parts of Asia such as Taiwan and Thailand.

"In preclinical studies, E-7046 combined with radiotherapy, chemoradiotherapy and with immune checkpoint inhibitors demonstrated antitumor activity in different malignancies, including colon rectal cancer, lung cancer and some PD-1-resistant tumor models," said Ruirong Yuan, chief medical officer at Adlai Nortye.

AN-0025 is a first-in-class EP4 antagonist that is believed to prevent the binding of prostaglandin E2 to its EP4 to change the immunosuppressive character of the tumor microenvironment.

"AN-0025 has a stronger ability to penetrate the cancer cells. It features low toxicity, high activity and high selectivity. We plan to launch it in China, the U.S. and EU in four to five years," said Fong.

Time for innovation

Founded in 2004, Adlai Nortye was not engaged in novel drug development until two years ago, when the company raised funds from a series A financing round to support its transformation.

"Our strategy is to prioritize the development and commercialization of the in-licensing products first as they take shorter time. Through this, we can generate revenue to increase the valuation of the company," said Fong. "Then, we can leverage the capital market to support our drug innovation."

In 2017, Adlai Nortye was listed on the National Equities Exchange and Quotations in China but then applied for a delisting in March 2018.

"We do consider seeking listing in Hong Kong by the end of November next year," Fong said. "There we will have a higher valuation."

Adlai Nortye has a few of self-developed drug candidates that need capital for further development.

One of them is a PD-1/L1 small-molecule inhibitor, which the firm co-develops with Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College. An investigational new drug application is expected to be filed with the U.S. FDA and China National Drug Administration (CNDA) in 2019.

Another one is AN-0015, an IDO small-molecule inhibitor jointly developed with Suzhou Guokuang Pharmaceutical Inc. It is now in preclinical stage and it aims to treat various tumor types.

Meanwhile, AN-3005 is a small-molecule inhibitor targeting stimulator of interferon genes. It can activate proteins in a signal transduction pathway in immune cells, induce various interferon and cytokines expression, change the tumor microenvironment and induce tumors to produce specific T cells, thereby eliminating tumor cells.

According to Fong, other self-developed innovative drug candidates of Adlai Nortye include CSF1R, WNT, A2A/A2B. Those are all immuno-agents, so it is still too early to know what indications they target.

Fong said he is optimistic about the innovation of drugs in China.

"Since 2015, the biopharmaceutical industry is booming in China thanks to the policy reform of the CNDA. There has been more venture capital ever than before, and more biopharma talent return from overseas. It is the right timing to engage in drug innovation," said Fong.