[AACR 2026] ABL Bio advances bispecific ADCs, eyes dual-payload shift

SAN DIEGO, Calif. -- Hong Sook / Korea Biomedical Review correspondent --

ABL Bio presented preclinical data for its bispecific antibody-drug conjugate (ADC) candidates and outlined a shift toward dual-payload strategies, as competition in the ADC field increasingly centers on payload innovation.

The company, along with its U.S. affiliate Neok Bio, showcased two bispecific ADC programs  -- ABL206 (NEOK001) targeting B7-H3×ROR1 and ABL209 (NEOK002) targeting EGFR×MUC1  -- at the American Association for Cancer Research (AACR) Annual Meeting 2026.

Both candidates have received Investigational New Drug clearance from the U.S. FDA and are set to enter phase 1 trials. In preclinical studies, they showed improved anti-tumor activity and safety signals compared with conventional ADCs, the company said.

CEO Lee Sang-hoon said clinical development will be led in the United States through Neok Bio, with initial clinical data expected next year.

Speaking on the sidelines of AACR, Lee said ADC development is shifting from target-based competition to payload-driven innovation.

“Payloads, not targets, are becoming the key determinant of competitiveness,” he said. “Dual-payload strategies and indication-specific approaches will shape future global leadership.”

An interview with ABL Bio CEO Lee Sang-hoon was conducted at the AACR venue in San Diego, Calif., covering oncology R&D trends, pipeline differentiation, Neok Bio’s strategy, and future directions in cancer drug development. (KBR photo)

ADC trends at AACR center on three pillars: payloads, RAS, T-cell engagers

Q: What key trends in anticancer drug development stood out at this year’s AACR?

A:

The direction is very clear this year. Compared with last year, the biggest increase was in bispecific ADCs, with a particularly noticeable rise in dual-payload approaches. Rather than the emergence of entirely new targets, the focus has shifted to more effective killing of cancer cells using established targets.

Dual-payload strategies were barely visible at last year’s AACR, but within a year, a large body of preclinical data has emerged, signaling a clear shift in global drug development trends.

Q: What is driving this transition toward dual-payload strategies?

A:

Existing topoisomerase-based payloads have been widely used in clinical settings, leading to resistance issues. Global pharma companies recognize that relying solely on traditional topoisomerase approaches will not be sufficient for next-generation ADCs.

Overcoming resistance has become the central challenge in ADC development, and dual payloads have emerged as a potential solution. While targets may appear critical, anti-tumor efficacy is ultimately determined by the payload. Bispecific antibodies serve as delivery mechanisms, but the real competition lies in payload innovation.

Q: What is the most critical factor in developing dual-payload ADCs?

A:

Simply combining two payloads is not enough. A true dual payload must outperform payload A alone, payload B alone, and even the combination of A+B administered separately. However, many AACR datasets show improvements over A alone but not necessarily over B.

This means true synergistic combinations are difficult to identify, making it one of the biggest challenges in ADC development today. Beyond efficacy, developers must also address resistance and durability simultaneously.

Ultimately, the key lies in balancing toxicity and efficacy -- the therapeutic window. Without achieving this balance, dual-payload ADCs will not be clinically meaningful.

Q: Beyond ADCs, what other research trends stood out?

A:

The biggest keyword this year is RAS targeting. Combination strategies with RAS inhibitors are central. Second is T-cell engagers, particularly CD3-based bispecific and trispecific antibodies.

Together with dual-payload ADCs, these three areas form the core pillars of current anticancer drug development.

‘Direct competition with China is unrealistic, so Korea should focus on specialization’

Q: Chinese companies are gaining strong momentum in oncology, including ADCs. How do you view the competitive landscape?

A:

Realistically, head-on competition with China is difficult. The sheer number of companies and the emergence of highly competitive players make it challenging. In areas such as dual payloads and novel combinations, Chinese firms are moving extremely quickly.

Q: What strategy should Korean companies adopt?

A

: We cannot win through sheer volume. It’s like the Olympics  -- you can’t beat China in total medal count. But you can still win in specific events.

The key is to define and focus on specialized areas. Simply following others is not a viable strategy.

Q: What could be Korea’s area of specialization?

A:

If we cannot compete on speed and scale, we must create meaningful differentiation — whether in targets, payloads, or clinical strategy. We need a clear answer to why we are pursuing a specific approach.

Q: What is the key competitive edge of ABL209?

A:

ABL209 is an EGFR×MUC1 bispecific ADC — a relatively uncommon combination. Data suggest that MUC1 expression increases following resistance to RAS inhibitors, providing a strong scientific rationale for dual targeting.

Another key point is antibody design. We reduced EGFR binding affinity and engineered the antibody to avoid binding to shed antigens. Anti-tumor activity has also been confirmed in multiple patient-derived xenograft (PDX) models. While it uses a topoisomerase payload, resistance has not yet become a major issue for this target combination.

Q: How is ABL206 differentiated?

A:

ABL206 targets B7-H3×ROR1. B7-H3 is highly competitive globally, so our differentiation lies in combining it with ROR1. However, since ROR1 has shown limited efficacy in solid tumors, its clinical performance remains to be validated.

We received feedback from U.S. principal investigators (PIs) at AACR and are planning a strategy focused on indications where proof of concept (PoC) can be achieved quickly, even if the market size is smaller.

Q: What is their current development status?

A:

First-in-human dosing for both candidates is expected to begin by the end of next month. Most bispecific ADCs presented at AACR remain in preclinical stages, so we believe we are relatively ahead globally.

Q: What comes after topoisomerase-based ADCs?

A

: ABL206 and ABL209, which are entering clinical trials, utilize topoisomerase-based payloads. However, internally, we view this as the final topoisomerase-based strategy. Moving forward, we plan to shift away from relying on these approaches and focus on dual-payload strategies.

Q: How advanced is ABL Bio’s dual-payload strategy?

A:

About four dual-payload combinations are set to enter the animal testing phase, and we are evaluating approximately three additional combinations.

This reflects a shift in ADC development. Previously, a single payload was often applied across multiple cancer types. Now, the optimal payload is increasingly considered indication-specific.

Q: When will dual-payload data be disclosed?

A:

We are currently focused on generating preclinical data. Meaningful results are expected next year, with plans to present them at conferences such as AACR.

‘Neok Bio has a four-pronged strategy and will advance to phase 2 on its own’

Q: Can you elaborate on Neok Bio’s business strategy?

A:

Neok Bio has four commercialization scenarios: licensing out after phase 2, M&A, Nasdaq listing, and direct commercialization through local partnerships. At this stage, M&A is the most ideal scenario -- developing data through phase 2 and then being acquired.

However, we are also keeping the option of direct commercialization open. In the U.S., even small biotech firms can build commercial organizations using external resources. If the asset is competitive, self-commercialization becomes a realistic option.

To support this, we plan to raise investment in the U.S. next year to fund pipeline development through phase 2 and maintain strategic flexibility. Ultimately, the company will make decisions based on clinical results and market response.

Q: What are the key challenges ahead for ABL Bio’s oncology pipeline?

A:

Ultimately, everything comes down to clinical data. Preclinical results are only preliminary indicators and cannot fully prove differentiation.

ABL206 and ABL209 have demonstrated scientific rationale and preclinical potential. The next step is to confirm whether that differentiation translates into clinical outcomes.

For ABL206, the key question is how effectively ROR1 works in solid tumors. For ABL209, it is whether the target combination delivers meaningful clinical benefits in patients.

At the end of the day, drug development is about finding answers through clinical trials. Preclinical work has limits -- validation must come from clinical data. Without results, there is no meaning.

Hong Sook