Abtis Co. Ltd., Dong-A ST’s newly incorporated subsidiary since December 2023, is making headway with its leading Claudin18.2-targeting antibody-drug conjugate (ADC) candidate, AT-211, according to Abtis CEO Taedong Han.

“About 80% of gastric cancers do not have HER2 overexpression, but 77% overexpressed Claudin18.2,” Han told Bio Korea 2024 audience members on May 9, stressing that AT-211 was found to be highly potent against cancer cells expressing Claudin18.2 in ADC cell viability studies.

Abtis, Dong-A ST, and ST Pharm Co. Ltd. are South Korean affiliates of Dong-A Socio Holdings, which has been involved in several cancer collaborations announced recently, including one between Dong-A ST and Shaperon Inc., of Seoul, South Korea, for nanobody-based drugs, and another for ST Pharm and Interon Laboratories Inc., of Newton, Mass., to discover small-molecule TNFR inhibitor candidates. Dong-A ST also made a ₩25 billion (US$18.45 million) investment on May 20 in Seoul, South Korea-based Idience Co. Ltd., an Ildong Pharmaceutical Co. Ltd. subsidiary, to become Idience’s second largest shareholder, as reported by BioWorld.

In the meantime, Abtis is focusing on AT-211, with pharmacokinetics studies further highlighting its linker to be highly stable in vivo, according to Han, and AT-211 showing higher stability than Astellas Pharma Inc.’s zolbetuximab. The therapy also had the highest therapeutic index among Claudin18.2-based ADC competitors, he said.

Suwon, South Korea-based Abtis’ assets are developed with its linker platform called Abclick.

“Three competitors [have] ongoing phase I studies in the U.S.,” Han said. “Abtis expects to enter the U.S. market as fourth or fifth” in development upon the U.S. FDA approving an IND sometime this year. 

Abtis is preparing IND submissions for AT-211 to launch U.S.- and Korea-based phase I studies in 2025 for solid tumors, including gastric, gastroesophageal junction and pancreatic cancer. The goal is to gain FDA approval of the candidate by 2032.

In its “Vision 2032” roadmap to become a “global top five ADC company” by 2032, Abtis is targeting $1 billion in corporate value through a potential public listing. As a privately held firm, short- to mid-term goals include building a fourth-generation linker platform, discovering new ADC projects and building an ADC contract development and manufacturing organization and ADC-biosimilar business by 2029.

Sang Jeon Chung founded Abtis in 2016, serving as chief scientific officer, as well as a professor at Sungkyunkwan University in Seoul, South Korea. Han became head of Abtis in February 2024, following his previous post of vice president at Dong-A ST from 2020 to early 2024. Prior to that, Han was principal researcher at Yuhan Corp. for more than 20 years, with a PhD in medicinal chemistry from Seoul-based Kyunghee University.

ADC trends and strategies: Abtis CEO

At Bio Korea, Han gave an overview of ADC trends and strategies, including the rise of Asia-based biotechs leading the increasing number of ADC deals worldwide.

By biotech prowess, Seagen Inc., Roche Holding AG, Gilead Sciences Inc., Immunogen Inc. and Abbvie Inc. landed in the top five for the number of drugs in development, followed by ADC Therapeutics SA, Daiichi Sankyo Co. Ltd., Mersana Therapeutics Inc., Astellas and Pfizer Inc., to round out the top 10.

Analysis by geographic distribution, however, showed Asia-based ADC biotechs outnumbered those from both the U.S. and Europe from 2019 to 2022, taking over U.S.-based companies that were dominant from 2000 to 2018.

Heralded as a next-generation cancer modality, ADCs are targeted cancer therapies comprising three parts: monoclonal antibody, linker and payload.

The global ADC market is expected to reach $25.46 billion by 2032.

“We saw the biggest growth in small-molecule drugs for cancer,” Han noted, “but the biggest deals were for ADCs. These deals occurred largely at the discovery stage, rather than in phase I or in the clinic, in the form of collaborations and co-development deals.”

Analysis of cancer deals from January 2018 to December 2022 showed small-molecule therapies transactions accounted for the largest share, with 562-related deals, followed by deals for cell and gene therapies (251), monoclonal antibodies (230) and multi/bispecific antibodies (89).

ADC-related deals came in fifth (87), followed by protein and peptide technologies (60) and vaccines (42).

By deal value and modality, however, ADCs outdid the rest, with 42 related deals accruing up to $2.25 billion from 2018 and 2022. In the same time frame, 58 cell and gene therapy deals totaled $1.2 billion. Forty-four multispecific and bispecific antibody deals totaled $886 million.

Most ADC deals were for preclinical candidates, with 52 agreements inked for discovery-stage assets and 22 for preclinical candidates. Five ADC deals were for phase I assets, four were for phase II assets and two were phase III assets. In totality, the biggest ADC transaction value was anchored in two launched therapies. 

To date, 15 ADCs have been approved worldwide, of which two were withdrawn by 2024.

Of approved ADC therapies, HER2-targeting Kadcyla (trastuzumab emtansine), from Roche's Genentech unit, posted $2.17 billion in sales in 2021, followed by Seagen and Takeda Pharmaceutical Co. Ltd.’s CD30-targeting Adcetris (brentuximab vedotin) with $1.3 billion, and Astrazeneca plc and Daiichi Sankyo's HER2-targeting Enhertu (trastuzumab deruxtecan) with $426 million. 

A total of 864 ADC candidates were reported by 2024, Han said. Of the 864, about half (427) were in active preclinical research, and 17% (143) reached the clinic. By study phase, about 10% were in phase III; 40% were in phase II; 4% were in phase I/II; and 26% were in phase I. “Most phase II assets are not new [assets] but [actually existing] ADCs seeking expanded indications,” Han explained.

In 2022, 33 new ADC candidates entered the clinic. Solid tumors were the most popular indication for the 33 assets (29), followed by blood cancers (4). Top antigen targets for the 33 were HER2, TROP2 and STING, followed by TAA, B7-H3, PD-L1, Nectin4 and EGFR, among others.

For payloads, Han noted that “half of clinically active ADCs used tubulin inhibitor payloads … [and] topoisomerase I inhibitors have overtaken DNA damaging agents to become the second most prevalent payload class active in the clinic.”

Along with TOP inhibitors like exatecan, tubulysin and SN-38, popular payloads included tubulin, including eribulin and MMAE; DNA damaging agents like duocarymycin, pyrrolobenzodiazepine and anthracycline; immune-stimulating antibody conjugates such as TLR8, TLR9 and STING; and RNA polymerase II like alpha-amanitin.

As for linkers, valine-citrulline was “by far the most popular linker” at all stages of development, Han said, although “a large percentage of ADC programs did not disclose linkers.”