Once hailed as a "next-generation anticancer drug" amid a fierce race to out-license technology, the Antibody-Drug Conjugate (ADC) is at a new crossroads, analysts said. The core of the next competition is not how many are developed, but who first overcomes the limits of current ADCs.
At the 4th Samsung Medical Center·Aimed Bio Antibody-Drug Conjugate (ADC) Conference held at the Westin Seoul Parnas in Gangnam-gu, Seoul, on the 28th, Chair Nam Do-hyun Aimed Bio(0009K0), Chair Kim Yong-ju LigaChem Biosciences(141080), CEO Park Tae-gyo IntoCell(287840), CEO Lee Sang-hoon ABL Bio(298380), and CEO Lee Sung-joo Orum Therapeutics(475830) agreed that the base of Korea's ADC industry has rapidly expanded over the past year.
Chair Nam said, "This year, it has reached the point where it feels odd if a domestic pharma or biotech company is not doing ADC."
But as the industry has grown, competition has become more intense. This is no longer an era when business viability comes just from making one ADC. Companies need to find better targets, reduce toxicity, and develop technology that delivers drugs precisely to where they are needed. At the same time, they must consider how to expand beyond ADCs to next-generation therapeutic technologies.
◇ Round 2 of the ADC race… focus on linkers and payloads to cut toxicity
The biggest limitation of current ADCs is toxicity.
An ADC is a therapy that links a drug that kills cancer cells to an antibody that homes to cancer cells. In theory, because the antibody finds the cancer cell and delivers the drug, it can reduce the impact on normal cells. But in actual clinical settings, unanticipated hematologic toxicity and other adverse events often emerge, preventing sufficiently high dosing.
Chair Kim Yong-ju said LigaChem Biosciences is strengthening efforts to analyze the correlation between in vivo drug exposure and toxicity by leveraging its large-scale clinical pharmacokinetic (PK) and pharmacodynamic (PD) data. The aim is to go beyond asking "which drug is effective" and use data to identify under what conditions toxicity appears.
IntoCell CEO Park Tae-gyo said, "By mechanism, ADCs are targeted therapies, but the way currently made ADCs actually behave is as cytotoxic chemotherapies," adding, "The technology has not advanced enough yet, which is why they are not being evaluated that way." Cytotoxic chemotherapies broadly attack rapidly dividing cells, while targeted therapies aim at specific proteins or genetic alterations present in cancer cells.
ADCs are largely composed of an antibody, linker, and payload. The antibody is the "guidance system" that homes to cancer cells, the linker connects the antibody and the drug and serves as the bridge that allows the drug to be released at the right time, and the payload is the anticancer component that actually kills cancer cells. Until now, ADC technology competition has focused on how precisely these three elements are combined.
But there is growing sentiment that it is no longer easy to differentiate just by combining these elements.
Chair Kim said, "The technology to conjugate a drug to an antibody is now something anyone can do," adding, "By itself, it is hard to differentiate." He continued, "To solve the innate problems of ADCs, we should focus more on linkers and payloads, which still have greater room for optimization."
As the ADC market expands, attempts to combine various technologies—such as bispecific antibodies or "dual payloads" that carry two types of anticancer agents—are also increasing.
ABL Bio is a representative example. CEO Lee Sang-hoon said, "We are a company that, while developing antibodies, came to combine bispecific antibodies with ADCs," adding, "We are currently studying whether leveraging the ability of bispecific antibodies to penetrate deep into tumor tissue can improve payload delivery efficiency."
Some urged caution. CEO Park said, "For ADCs, the antibody, linker, drug, and even the combinations of linkers and drugs each need to be optimized," adding, "On top of that, stacking bispecifics or other elements to optimize every combination simultaneously is, in reality, far too complex."
In other words, just because a bispecific antibody homes to cancer cells better does not mean that attaching it to an ADC will yield an optimal therapy. Park said, "It is necessary to take on new technologies, but we must soberly assess the chances of success," adding, "It is important to focus on the direction with the highest likelihood of success."
◇ ADCs alone aren't enough… "We look for the technology needed in five years"
The discussion goes a step further: preparing for "what comes after ADCs."
Chair Kim Yong-ju said recent efforts at LigaChem Biosciences are widening the view beyond ADCs, adding, "We want to keep only what ADCs do well and change everything else."
For now, the focus is on how to deliver drugs. Kim said, "These days we are meeting many companies with diverse drug delivery technologies," adding, "By changing formulations or using new carriers, there may be a chance to modulate in vivo exposure and reduce toxicity."
Orum Therapeutics is developing DACs that combine ADCs with targeted protein degradation (TPD) technology. CEO Lee Sung-joo said, "We were focused only on cancer drugs, but recently we started applying our technology to other areas," adding, "When we said in 2019 that we would do DACs, many asked why we were doing that. Among the things people ask 'why' about now, we are constantly thinking about which technologies will be needed in five years."
CEO Lee Sang-hoon stressed that to do so, companies must closely watch changes in the external market. He said, "ABL Bio's blood-brain barrier (BBB) shuttle technology and small interfering RNA (siRNA) research began that way," adding, "In discussions with global pharma, we picked up signals that existing antibody technology alone might be insufficient, and we linked that to a new research direction."
All of this ultimately requires money. Although LigaChem Biosciences recently secured about 500 billion won through the Public Growth Fund, Chair Kim said he is actually "worried because there are too many places to spend it." He said, "We are currently conducting multiple ADC clinical trials, and the number of programs entering the clinic continues to grow," adding, "Once you run trials, you realize just how much money it takes."
Orum Therapeutics, which holds about 250 billion won in cash, also plans to invest most of it in developing new payloads and clinical research. CEO Lee Sung-joo said, "The reason we raised convertible preferred stock (CPS) at the end of last year was not because we immediately needed funds," adding, "We secured capital with the mindset that when a good wave comes, you have to ride it."
There were also calls for investors to be more actively involved in the ADC industry. Chair Kim said, "ADC chemistry, manufacturing and controls (CMC) is 'hell,'" adding, "Clinical physicians and investors must be at the table for these discussions."