[Edaily Reporter KIM SAE-MI ] The prospect of submitting a Biologics License Application (BLA) to the U.S. within the year for “Tobesimig” (ABL001), a bispecific antibody for bile duct cancer developed and licensed by ABL Bio Inc.(298380), has become uncertain. This follows a recommendation by the U.S. Food and Drug Administration (FDA) that a clinical trial demonstrating a survival benefit be conducted prior to BLA submission.

Compass Therapeutics, which has licensed the global rights to “Tobeshimig” (excluding South Korea) and is currently developing the drug, has expressed disagreement with the FDA’s recommendation and stated that it will continue further discussions. However, Compass’s stock price plummeted by more than 30% in a single day on the 22nd (local time), the day the FDA’s recommendation was made public.

FDA: “Demonstrate survival benefit prior to BLA submission”… Compass stock plunges 31.87%

According to the biotech industry on the 23rd, Compass Therapeutics announced that on the 22nd, the FDA recommended conducting a clinical trial to demonstrate a survival benefit before submitting a Biologics License Application (BLA) for tobesimig in patients with advanced biliary tract cancer who have received prior treatment. In response, Compass stated, “This was not the response we anticipated.”

Thomas Schutz, CEO of Compass, said, “We respect the FDA’s feedback, and our priority is to work with the FDA to determine the best path forward to support our planned BLA submission.”

However, Compass maintains that it does not agree with the FDA’s determination that a new clinical trial is necessary prior to BLA submission. Compass plans to continue preparing for BLA submission while engaging in further discussions with the FDA based on the efficacy confirmed in the Phase 2/3 clinical trial (COMPANION-002).

The market reaction was lukewarm. On the 22nd, Compass closed at $1.24 (1,684 won) on the Nasdaq, down $0.58 (31.87%) from the previous trading day’s close of $1.82 (2,471 won). Trading volume also surged to 27,202,788 shares. Based on the closing price, the company’s market capitalization shrank to $223 million (302.8 billion won). Based on a simple calculation using the previous trading day’s share price, this means approximately $100 million (135.8 billion won) in market capitalization vanished in a single day.

The market appears to have interpreted the possibility that the FDA might require additional survival trials as a de facto prerequisite for BLA submission as a risk of delay in the approval timeline.

ORR and PFS Improved, but OS Remains a Stumbling Block… “Need to Prove Survival Benefit”

The FDA’s demand for

proof

of

survival benefit

stems from the overall survival (OS) results of the COMPANION-002 trial.

COMPANION-002 is a Phase 2/3 clinical trial that randomly assigned 168 patients with previously treated, unresectable, advanced, metastatic, or recurrent biliary tract cancer in a 2:1 ratio to either the tobesimig/paclitaxel combination group (111 patients) or the paclitaxel monotherapy group (57 patients).

Based on the final independent central review (BICR), the objective response rate (ORR) was 18.0% (20 patients) in the combination group and 5.3% (3 patients) in the control group. Statistical significance was also achieved (p=0.0228). The ORR, initially reported as 17.1%, was revised upward to 18.0% after one patient was reclassified as having a partial response (PR).

The median progression-free survival (PFS) was 4.7 months in the combination group and 2.6 months in the control group. The hazard ratio (HR) was 0.44, indicating that the risk of disease progression or death was 56% lower in the tobesimig combination group (p<0.0001).

The issue lies with overall survival (OS). In an intention-to-treat (ITT) analysis of all randomized patients, the median OS was 8.9 months in the tobesimig combination group and 9.4 months in the control group. The hazard ratio (HR) was 1.05, with a p-value of 0.78, failing to reach statistical significance.

Compass has explained that the OS analysis was influenced by the fact that 31 patients (54%) in the control group were crossed over to the tobesimig combination therapy after disease progression. In fact, the median OS for patients who crossed over was 12.8 months, while the remaining 26 patients who did not receive tobesimig had a median OS of 6.1 months.

This is a post hoc subgroup analysis rather than a direct comparison based on random assignment. It is difficult to rule out the possibility of selection bias, as the health status of patients who were able to receive follow-up treatment after disease progression may have influenced the results. This is interpreted as the reason why the FDA viewed the lack of a direct survival benefit in the randomized ITT analysis as a significant concern.

From Compass’s perspective, the key issue is the extent to which the FDA will accept the argument that the difference in OS was diluted due to cross-treatment. If the FDA maintains its current position and requires a new survival trial, disruptions to the development schedule—which had aimed for a BLA submission within the year—will be inevitable. This is because a new clinical trial would require a significant amount of additional time, from patient recruitment to follow-up.

What is the impact on ABL Bio Inc.?

Tobesimig is a bispecific antibody developed by ABL Bio Inc. that simultaneously targets DLL4 and VEGF-A. Its mechanism of action involves simultaneously blocking the two pathways involved in tumor angiogenesis.

According to Compass’s second-quarter report this year, ABL Bio Inc. received an upfront payment of $5 million (6.8 billion won) and development milestones totaling $6 million (8.1 billion won) in exchange for licensing the global rights to Tobesimig, excluding South Korea. In the future, the company could receive up to $96 million (129.9 billion won) in development and regulatory milestones in the oncology field, up to $303 million (409.9 billion won) in commercialization milestones, and single-digit tiered royalties based on net sales.

It has not been disclosed at which stage—BLA submission, FDA acceptance of the BLA, or final marketing approval—these milestones will be triggered. Therefore, it is currently difficult to gauge the direct impact this FDA recommendation will have on ABL Bio Inc.’s remaining milestones. However, if the FDA requires additional survival studies as a prerequisite for BLA submission, the U.S. approval timeline could be delayed, potentially pushing back the timing of regulatory milestone payments and future sales royalties.

The next pivotal event is the European Society for Medical Oncology (ESMO) conference, scheduled for next month. Compass plans to present the full data from COMPANION-002 in an oral presentation at ESMO 2026 on the 24th of next month. As detailed data—including cross-over results and OS subgroup analyses—will be disclosed, this presentation is expected to provide insights into further discussions with the FDA and the direction of the future U.S. approval strategy.