Antibody-Drug Conjugate (ADC) platform corporations IntoCell(287840) is shifting its business center of gravity from a "company that sells technology" to a "company that also directly creates new drug candidates."
IntoCell plans to increase the number of ADC candidates it develops in-house this year from five to 10. It judged that it has become difficult to sign large technology export deals with global pharmaceutical companies based on new linker or payload technology alone. It said it must directly secure new drug candidates, the so-called "assets," with real efficacy and safety data.
IntoCell held a press briefing on the 19th at the CCMM Building in Yeouido, Seoul, and unveiled this pipeline expansion strategy and the status of new technology development.
Park Tae-gyo, IntoCell's CEO, said, "We have finalized the targets for two of the five new candidates to be added, and we are reviewing the remaining three."
The first follow-up pipeline, a 5T4-targeting ADC, entered preclinical studies in May. The goal for the DLL3-targeting ADC is to begin preclinical studies in 2027. The company is reviewing PSMA and HER3 among the remaining three target candidates and plans to finalize them within the year.
ADC is a therapy that attaches a drug that kills cancer cells to an antibody that homes in on cancer cells. If the antibody is a "guidance system" that seeks out cancer cells, the drug (payload) is the "warhead," and the ring that connects the two is the linker. Until now, IntoCell's main business was transferring this linker and payload technology to other pharmaceutical and bio corporations.
However, going forward, the strategy is to also increase the share of technology exports in which it develops its own candidates through preclinical or early clinical stages to secure data directly. Seo Young-seok, IntoCell's chief financial officer (CFO), said, "Fully developing our own new drugs to the end is a goal for the 2030s and beyond."
◇ A new "warhead" that cleared patent hurdles… performance comparison with Enhertu
To expand the pipeline, the technologies to be applied must also diversify. IntoCell unveiled a new payload on the day.
The payload is the drug that actually attacks cancer cells after the ADC enters them. Even if the antibody precisely finds cancer cells, it is difficult to achieve sufficient therapeutic effect unless the payload's performance supports it.
IntoCell has focused on the Nexatecan (NxT) series payloads it developed in-house. However, the existing key candidate "NxT3" faced limitations in use due to prior patent issues by a Chinese corporation.
IntoCell developed "NxT32" and "iNxT3" to replace it. In particular, unlike existing Nexatecan, iNxT3 is characterized by improved physicochemical properties through increased water solubility. If a drug is excessively lipophilic, the ADC itself may aggregate or the likelihood of affecting normal cells may increase.
According to animal study results disclosed by the company, in a 5T4 model, an ADC applying iNxT3 showed stronger tumor suppression even at one-fourth the dose compared to a DXd-based ADC used in "Enhertu (trastuzumab deruxtecan)." Enhertu is a HER2-targeting ADC discovered by Daiichi Sankyo and co-developed and commercialized with AstraZeneca.
Park said, "We did not develop the new payload simply as a substitute for existing drugs; we secured a new weapon to apply across multiple pipelines going forward."
However, since these are animal study results, whether the same effect will appear in people must be confirmed through clinical trials.
◇ It is not enough to increase only the warheads… "link" TBA linker in the final stage
If the new payload broadened the options for warheads to attack cancer cells, the linker is the technology that increases the ways to connect that warhead to the antibody.
IntoCell's existing main linker, "OHPAS," has strengths in consolidating drugs with specific structures. However, it is difficult to apply to drugs with different structures, such as iNxT3.
IntoCell is developing the "TBA linker" to overcome this limitation. Once development is complete, drugs with alcohol groups, like iNxT3, can also be consolidated to antibodies. An alcohol group is a specific chemical structure attached to a drug molecule and is one of the factors that determines through which linker it can bind to an antibody.
IntoCell said that in a HER3 animal model, an ADC combining TBA and iNxT3 showed a level of tumor suppression similar to that of an ADC using the existing GGFG linker. It is currently conducting final optimization to ensure strong action against cancer cells while reducing effects on normal cells.
◇ "Different combinations for each pipeline… spreading development risk"
Another reason IntoCell is expanding its technology options is to diversify development risk.
In ADCs, efficacy and safety vary depending on which payload and linker are combined with which antibody. If a problem arises with a single linker or payload, multiple candidates applying it may be affected together.
IntoCell plans to apply different linkers and payloads to each candidate going forward. For the ongoing clinical B7-H3 target "ITC-6146RO," it is applying the existing OHPAS series technology, and for follow-up pipelines such as 5T4 and DLL3, it will combine the new payload with other linkers such as TBA or GGFG.
The strategy is to develop multiple technology combinations and candidates simultaneously rather than betting the company's future on a single technology.
While expanding its own pipeline, it will also continue to expand its existing technology export business. IntoCell signed confidentiality disclosure agreements (CDAs) with four overseas corporations and four domestic corporations, and with three of each it has even concluded material transfer agreements (MTAs) and is conducting technical reviews.
In the past month, it signed a commercial license agreement (CLA) with Samsung Bioepis for a nectin-4-targeting ADC. The two companies first advanced the research collaboration agreement signed in 2023 to discover up to five ADC candidates into an actual business contract.
IntoCell's in-house pipeline ITC-6146RO is in phase 1a at three hospitals in Korea. The company expects to be able to review interim data around the end of the year.