HONG KONG – Singapore's Aslan Pharmaceuticals Ltd. and South Korea's Bukwang Pharmaceutical Co. Ltd. have jointly established a new company dedicated to the development of aryl hydrocarbon receptor (AhR) drug candidates. Named Jaguahr Therapeutics Pte. Ltd. – the unusual spelling a clear reference to "AhR" – it will be based in Singapore and will focus on developing immuno-oncology therapeutics for global markets based on the preclinical AhR antagonists in Aslan's early stage pipeline.

Under the terms of the agreement, the global rights to all of the assets related to AhR technology will be transferred to the new JV. Seoul-based Bukwang will inject $5 million into Jaguahr to fund the development of the AhR assets.

"Bukwang has a strong track record as one of South Korea's leading pharmaceutical companies," Carl Firth, founder and CEO of Aslan, told BioWorld. "The team has already demonstrated its intention to work together in a very collaborative way and that's a fundamental driver for us in selecting partners for our assets.

"It was important for us to identify a partner who shares our commitment to working quickly and smartly in order to progress these assets through early stage development efficiently and that's what we identified in Bukwang," he added.

Aslan's AhR antagonists have been discovered and developed by the company and its collaborator, Mark Graham. AhR is a druggable transcription factor that acts as a master regulator of the immune system. The enzymes IDO1, IDO2 and TDO are frequently overexpressed in multiple tumor types and convert tryptophan into kynurenine (KYN) in the tumor microenvironment. KYN signaling via AhR in dendritic cells and effector T cells converts them into regulatory T cells that act to suppress the immune response.

Research has demonstrated that the unique advantages of AhR antagonists include broadly inhibiting the signaling of all AhR ligands produced by any enzyme that metabolizes tryptophan, and robust activation of the immune response to kill cancer cells, according to Aslan.

"Targeting the AhR pathway is a novel approach in modulating tumor immune system and thus we see an enormous potential in drugs targeting AhR," said Riswanto, Bukwang's global business development manager. "Going forward, Bukwang's R&D strategy remains flexible with added interest in central nervous system (disorders) and immuno-oncology."

Determined to advance the development of AhR drug candidates quickly, Jaguahr will work to identify a lead development compound as early as next year.

"We have several chemical series and possible candidates," said Aslan's Firth. "We expect to put forward a candidate drug in 2020."

He told BioWorld that there is no set timeline for regulatory approvals yet, but the company hopes to file an IND in 2021.

"The initial market for filing will depend on where the first clinical studies are run, which has yet to be determined, but we would expect the IND to eventually be filed in major markets, including the U.S.," said Firth. "Jaguahr will be responsible for regulatory affairs in all markets, with additional support from Aslan and Bukwang teams."

Progressing pipeline

By setting up the new JV, Aslan will be able to call forth all its energy to develop the four compounds currently in its clinical pipeline: varlitinib, ASLAN-002, ASLAN-003 and ASLAN-004.

"Aslan has a broad clinical pipeline with a lead asset, varlitinib, in a pivotal study due to read out later this year," said Firth. "Our focus is and remains on progressing our clinical pipeline. When the AhR program approaches the clinic, we may consider bringing the asset back into our portfolio."

Varlitinib is an oral, reversible, small-molecule HER inhibitor. Aslan recently presented new data from the phase Ib open-label, dose-escalation study in combination with modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) chemotherapy to determine the safety, tolerability and maximum tolerated dose (MTD) in advanced solid tumors. The MTD of varlitinib combined with mFOLFIRI was 300 mg twice daily, administered orally. Durable response in HER2-positive ovarian clear cell cancer was seen and warrants further investigation.

Varlitinib has been granted orphan drug designations in the U.S. for gastric cancer and cholangiocarcinoma as well as in South Korea for biliary tract cancer.

ASLAN-002 is small-molecule inhibitor of RON and cMET receptor tyrosine kinases; ASLAN-003 is an orally active inhibitor of DHODH; and ASLAN-004 is a fully human monoclonal antibody that targets the IL-13Rα1. Both ASLAN-002 and ASLAN-004 are in phase I trials, while ASLAN-003 is in phase II studies.

A prominent pharmaceutical company in South Korea, Bukwang was established in 1960 and has been listed on the Korea Stock Exchange since 1988. The company mainly focuses on the treatment of liver, metabolic, central nervous system diseases and oncology. Two of its lead assets – a D2/5HT2A-R antagonist for schizophrenia and bipolar depression and a VEGFR2 inhibitor targeting gastric cancer – have entered phase III trials.

Aslan's shares (NASDAQ:ASLN) closed at $1.66 on Oct. 1, down by 4% from the previous day's $1.73 after news of the JV deal. Bukwang's stock (KRX:003000) closed at KRW13,800 (US$11.46) on Oct. 2.

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