Korea Stepping Up IO R&D To Catch Up With Global Players, Trends

Immuno-oncology deals and R&D by South Korean companies are picking up speed as they are put more focus on the hot sector in line with global trends.

South Korean companies are beginning to see progress in immuno-oncology research and development as they strive to catch up with major IO players and global trends.

IO has been one of the most promising and fastest growing fields of cancer research and also one of the most active areas in terms of licensing deals and acquisitions in the past few years. Such trends are expected to continue this year, with more advances expected in the R&D of I-O including combination therapies. (Also see "What Does 2018 Hold For Biopharma?" - Scrip, 29 Dec, 2017.)

In line with global R&D trends, South Korean companies are increasingly putting their focus on this hot area, with some of them yielding meaningful results in recent months, although their IO research still largely remains in the early stages.

Dong-A ST’s IO Deals

Among South Korean companies, Dong-A ST Co. Ltd. appears to be standing out in early stage R&D, reaching a couple of IO deals amid its ongoing general efforts to beef up novel drug development via open innovation. Earlier this month, the South Korean pharma agreed with AstraZeneca PLC on the sidelines of the JP Morgan Healthcare Conference in San Francisco to jointly research innovative immuno-oncology drugs.

Under the agreement, the two firms will jointly explore lead compounds and drug candidates from AstraZeneca's three immuno-oncology drug targets. The two will jointly own all the intellectual property and patents stemming from the joint research. Further details of the deal weren't disclosed.

The latest collaboration follows Dong-A’s sizable licensing and co-development agreement in December 2016 with AbbVie Biotechnology, a subsidiary of AbbVie Inc., for the South Korean pharma's early stage Mer tyrosine kinase inhibitor candidate. The deal was worth up to $525m plus sales royalties. (Also see "AbbVie Picks Up Dong-A Candidate As It Makes Immuno-Onc Inroads" - Scrip, 29 Dec, 2016.)

Under the deal, Dong-A ST and AbbVie will jointly develop the still preclinical stage molecule until submission of an IND to begin clinical trials. After this filing, AbbVie will exclusively own the global rights, excluding South Korea, for the development and commercialization of the asset.

Dong-A ST has been developing IO drug candidates largely via its novel innovative drug research center, which is primarily focusing on oncology and IO.

“Companies developing early-phase IO candidates can look to partner with companies with a larger presence in the IO space, like Dong-A ST has partnered with AbbVie and AZ. This increases exposure and speeds up development of these products in the major markets,” Datamonitor Healthcare analyst Hardik Patel told Scrip.

Genexine’s Deal, Other Progress

Another notable IO achievement from the country was the licensing out agreement reached by South Korean biotech Genexine Inc. in December last year. It inked a $548m-plus licensing out pact for its proprietary long-acting immuno-oncology drug candidate HyLeukin with the Shanghai-based I-MAB Biopharma.

HyLeukin, also known as GX-I7, is an immuno-oncology agent comprising an optimally engineered Interleukin-7 (IL-7) molecule based on Genexine’s proprietary long-acting protein platform technology, focusing on cancer, infectious diseases and lymphopenia. (Also see "Genexine Seals I-O Licensing Deal With I-Mab, Builds Momentum" - Scrip, 26 Dec, 2017.)

HPV therapeutic DNA vaccine GX-188E is Genexine's another IO drug candidate under clinical development. It is undergoing Phase II studies for cervical intraepithelial neoplasia and is also gearing up for a Phase Ib/II clinical trial in combination with Keytruda (pembrolizumab) for the treatment of patients with HPV-induced advanced non-resectable cervical cancer.

In September 2017, Chinese active pharmaceutical ingredients (API) manufacturer Zhejiang Huahai Pharmaceuticals Co. Ltd. agreed to invest $30m for a significant stake in the Korean biotech startup Eutilex Co. Ltd., plus an additional $8.5m to obtain exclusive rights to Eutilex's IO asset EU101. (Also see "Chinese API Maker Huahai Leaps Into IO Via Korean Startup" - Scrip, 7 Sep, 2017.)

EU101 is a monoclonal antibody agonist that binds 4-1BB. It is being studied alone and in combination with checkpoint inhibitors PD-1/PD-L1.

The South Korean biotech also has various 4-1BB CTL (adoptive T-cell therapy), CAR-T and eTCR-T pipeline assets as well as a monoclonal antibody pipeline.

Meanwhile, ImmuneOncia Therapeutics Inc., a joint venture between leading South Korean pharma Yuhan Corp. and US-based Sorrento Therapeutics Inc., is known to be the only South Korean pharma that is progressing with development of PD-L1 inhibitors. Its most advanced program is IMC-001, a fully human anti-PD-L1 monoclonal antibody, which shows robust efficacy both in vitro and in vivo. It is in investigational new drug (IND) application-enabling studies and is expected to enter clinical development soon. (Also see "ImmuneOncia: A PD-L1 Latecomer Hoping To Break Into The Market" - Scrip, 16 Nov, 2017.)

ImmuneOncia’s pipeline also includes anti-CD47 mAb and bispecific antibodies.

Clinical Trial Progress

South Korea has also seen a progress in IO clinical trials.

SillaJen Inc. is the only South Korean company which is progressing late phase global clinical trials of its IO drug candidate, conducting a global Phase III study for its oncolytic immunotherapy Pexa-vec (pexastimogene devacirepvec) with its partners for hepatocellular carcinoma.

A Phase III study, PHOCUS, of Pexa-Vec in patients with HCC started in 2016, with the first European patient being enrolled in April 2017. Transgene SA, an Institut Mérieux subsidiary, has exclusive rights to develop and commercialize Pexa-Vec in Europe, while the licensor SillaJen Inc. is focused on developing Pexa-Vec for the North American market. SillaJen has also licensed rights in China and Hong Kong to Lee's Pharmaceutical Holdings Ltd.

In July last year, SillaJen and Lee's Pharmaceutical received approval from the China FDA to conduct a Phase III study for advanced liver cancer using Pexa-Vec.

It is also collaborating with research institutes and global pharmas for Pexa-Vec's use as a combination cancer therapy. In August 2017, it reached agreement with the National Cancer Institute for the development of a combination therapy for colorectal cancer. The two sides will evaluate the combination of SillaJen's Pexa-Vec with anti-PDL1 and anti-CTLA4 antibodies in an early phase clinical trial in patients with advanced colorectal cancer.

Meanwhile, BR-VigenCell, which is a subsidiary of Boryung Pharmaceuticals Co. Ltd., received IND approval from the MFDS in December last year to begin a Phase II study of its T-cell immunotherapy (Epstein Barr-virus-cytotoxicity T lymphocytes) to treat Epstein Barr-virus positive NK/T-cell lymphoma patients.

Global IO Trends

Datamonitor analyst Patel noted that the mechanisms targeted by these drug candidates may not be among the most prominent mechanisms that are closest to market.

According to Datamonitor Healthcare's Immuno-oncology Overview published in December, the PD-1/PD-L1 inhibitor and TCR/CAR-T therapy drug classes lead development of all immuno-oncology drugs. However, several novel mechanisms of action are also in early-phase development.

Developers of approved PD-1/PD-L1 inhibitors – Bristol-Myers Squibb, Merck & Co, Roche, AstraZeneca, and Pfizer – currently dominate the immuno-oncology field in terms of the number of ongoing, conducted, and planned trials.

Furthermore, PD-1/PD-L1 inhibitors remain a focal point of immuno-oncology combinations, with various types of combination approaches being studied.

Of the 4,153 immuno-oncology trials identified in the Trialtrove database, 1,927 trials (47%) are testing a combination featuring an immuno-oncology drug.

Meanwhile, South Korea ranked the 13th country in terms of the number of immuno-oncology clinical trials, among the top 25 countries where I-O trials are being conducted, Datamonitor said.

More Korean Companies Diving Into I-O

Amid the increasing importance of IO, companies like ViroMed Co. Ltd. and LG Chemhave recently declared that they will expand or enter their immuno-oncology R&D.

During the JP Morgan Healthcare Conference 2018 in San Francisco, LG Chem, which has merged with LG Life Sciences, presented information that it will focus its R&D capacity in the immuno-oncology and metabolic disease areas as well as speed up expanding novel drug pipelines using open innovation.

Meanwhile, ViroMed unveiled plans in November last year to develop three more CAR-T therapy candidates, and to initiate clinical trials of these for blood and solid cancer during 2020 to 2022. (Also see "ViroMed Steps Up Global Ambitions With New Gene Therapy Pipeline" - Scrip, 23 Nov, 2017.)

From the editors of PharmAsia News.

[Editor’s note: For more information, see Datamonitor Healthcare’s in-depth report on Immuno-oncology Overview .]

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