HONG KONG – Huya Bioscience International LLC, which has a special interest in China-developed assets, has obtained an exclusive global license, bar China, for the SHP2 inhibitor HBI-2376 from Suzhou-based Genhouse Pharmaceutical Co. Ltd. Financial terms were not disclosed.

 “We are planning to conduct the necessary studies to advance HBI-2376 to investigative new drug filing in the U.S. in the near future,” Huya’s director of communications Yiota Merianos told BioWorld. “Extensive biochemical characterization has shown that HBI-2376 is a highly potent and selective inhibitor of SHP2 phosphatase. Furthermore, preclinical investigations showed significant efficacy for HBI-2376 as a single agent or in combination with other small molecule inhibitors or checkpoint inhibitors in multiple tumor models.”

With offices in the U.S., Japan, South Korea and a few other countries, Huya has focused on bringing assets originating in China to the global market through licensing deals. Merianos said the company has built a China-sourced portfolio covering all therapeutic areas and looks to license products for global development. The decision to license in HBI-2376 from Genhouse was due to high demand for safe and effective cancer treatments, he said.

HBI-2376 is an oral small molecule inhibitor of SHP2, an important component of the RAS signaling pathway that leads to activation of ERK/MAPK pathways in cancer cells. SHP2 is crucial for the treatment of multiple tumor types whose cellular growth is dependent on the activity of receptor tyrosine kinases in the mitogen-activated protein kinase or MAPK pathway.

This is because SHP2 interaction with the immune checkpoint molecule PD-L1 results in the inhibition of T-cell activity in the tumor microenvironment. Due to this possibility of inhibition to enhance T-cell immunity, SHP2 may have greater potential relative to the success of PD-L1 checkpoint inhibitors. SHP2 also has multiple functions in tumor progression, cancer cell growth and the suppression of anti-tumor immunity, allowing it to be applied in different forms of cancer treatment.

Huya has three other products in its pipeline, including its lead program HBI-8000, an epigenetic drug.

Belonging to the benzamide class of histone deacetylase inhibitors (HDACIs), HBI-8000 works by controlling how tightly DNA is wound around histone proteins which regulate gene expression. This contributes to increased tumor immunity by altering the tumor microenvironment and expression of several proteins involved in the growth processes of cancer cells.

“HBI-8000 is the first approved, oral class I selective HDACI. Based on clinical results, the Japanese Pharmaceutical and Medical Devices Agency (PMDA) allowed accelerated development of this drug in lymphoma,” said Merianos. “Currently, we have two ongoing registration clinical studies in Japan, investigating the use of HBI-8000 in peripheral T-cell lymphoma for which the PMDA granted orphan drug status, and adult T-cell lymphoma.”  

With evidence suggesting that HBI-8000 increases the efficacy of other cancer agents, combination trials will be a main focus for the novel epigenetic drug in the future.

“Due to its immunomodulatory properties, we are also conducting a phase II trial of HBI-8000 in the US, investigating efficacy and safety in combination with nivolumab for the treatment of solid tumors. Huya Bio will pursue trials for HBI-8000 in combination with checkpoint inhibitors and other anti-cancer therapeutics with the aim of meeting unmet medical needs in oncology,” said Merianos.

Although both HBI-2376 and the HBI-8000 lead program are both oncology-focused, Merianos said that does not mean that Huya is putting a higher emphasis on oncology in its future development plans. It is also looking to strengthen its cardiovascular portfolio, he said.

Two products in the cardiovascular field in its pipeline include HBI-3000, a multi-ion channel blocker in development for the treatment of cardiac arrhythmias which can be used to treat patients with atrial fibrillation, and HBI-3802, a small molecule which showed unique preclinical activity in regenerating cardiac muscle cells damaged by ischemia.

For HBI-3000, its phase I study conducted in the UK was successfully completed at the end of February this year. A phase II dose escalation study of this compound in acute AF is planned.

China will also continue to be the company’s point of focus despite it having presence in other parts of Asia including Japan and South Korea, as well as abroad in the U.S, and similar licensing deals like the HBI-2376 could be seen in the future.

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