BEIJING – Shenzhen-listed Chinese firm Nanjing Hicin Pharmaceutical Co. Ltd. has in-licensed an isocitrate dehydrogenase (IDH) inhibitor known as I111b from Italian oncology specialist Nerviano Medical Sciences Srl (NMS) to develop and commercialize the drug globally for patients with acute myeloid leukemia (AML).

Under the terms, Hicin will pay €750,000 (US $841,180) up front and up to €21.75 million in milestone payments once the currently preclinical candidate is approved in any major market. The Chinese firm is also paying NMS a 3.5% royalty on sales.

"We aim to in-license innovative drug candidates to continue developing them in order to enrich our product pipeline," Jin Lu, Hicin's board secretary, told BioWorld. "NMS has comprehensive experience from innovative drug discovery to drug registration and it has out-licensed assets to other companies that were successfully marketed afterwards."

NMS is preparing the candidate for preclinical development at the moment and is expected to deliver it to Hicin in 2020. "We will then continue to advance I111b to pre-IND studies, clinical trials, registration, manufacturing and commercialization," Lu added.

The I111b project is a new oral small-molecule designed to act on IDH mutation sites in tumor cells to reduce 2-hydroxyglutarate and induce histone demethylation to eventually inhibit tumor growth.

AML is the most common type of leukemia diagnosed in adults and children – an estimated three to four people out of 100,000 people – with a five-year survival rate of around 27%. Currently, the U.S. FDA has approved two IDH inhibitors for marketing: Idhifa (enasidenib, Celgene Corp. and Agios Pharmaceuticals Inc.) and Tibsovo (ivosidenib, Agios Pharmaceuticals Inc.) for relapsed or refractory AML. (See BioWorld, Aug 2, 2017, and July 20, 2018.)

The oral therapy Idhifa is the first and only one that the FDA has approved to treat patients with an IDH2 mutation, whereas Tibsovo became the first FDA-approved therapy to address IDH1 mutation.

In Asia, Agios has partnered with Suzhou-based Cstone Pharmaceuticals Ltd. to develop and commercialize ivosidenib as a monotherapy or in combination efforts. The two entered a potential $424 million deal in June last year covering China, Hong Kong, Macau and Taiwan. (See BioWorld, June 27, 2018.)

While FLT3 inhibitors and CD33 inhibitors have also been approved to treat AML, Hicin said IDH inhibitors show great potential. "The mechanism of action of IDH inhibitors is well-proven, so the risk is lower for us to develop IDH inhibitors in the early stage," Lu explained.

He added that IDH inhibitors are undergoing clinical trials for more indications. Tibsovo has met the endpoints in phase III trials for bile duct cancer. Its developer Agios also has AG-881 (vorasidenib), an oral inhibitor of both the IDH1 and IDH2 proteins, in phase I trials for malignant solid tumors such as gliomas, as well as malignant hematological tumors such AML and myelodysplastic syndrome.

Last year, Idhifa and Tibsovo generated $20 million and $13.8 million in revenue in the U.S., respectively.

"If I111b is developed and marketed successfully, it will help a lot of patients and create enormous social and economic benefits," Lu said.

Last year, Hicin was part of a Chinese consortium to acquire a 90% stake in NMS in a €300 million transaction. The leading investor SARI, an affiliate of the Shanghai Advanced Research Institute created to invest in biotech companies, set up a special fund joined by Hicin, Yicun Capital and other partners. After the transaction was finalized in March, Hicin started promoting collaborations with NMS to develop innovate drugs.

Hicin said the acquisition, and the latest in-licensing agreement, will help transform the company into an innovation-based drugmaker and expand its presence in that arena. Previously, the company had developed torasemide for injection, a first of its kind in China.

Before switching its area of focus, the Chinese firm offered drugs for orthopedics, along with antivirals, anti-infectives, immune regulation drugs and products targeting digestion. It also manufactured active pharmaceutical ingredients through its subsidiary. In 2017, the firm went public in Shenzhen.

NMS is a major Italian developer of innovative cancer drugs and provides preclinical, clinical and production services to drugmakers at home and abroad.

Its pipeline includes danusertib, encorafenib and entrectinib. In November 2013, it out-licensed entrectinib to San Diego-based Ignyta Inc., which was later acquired by pharma giant Roche Holding AG.

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