BTN1A1 effective in PD-L1–negative, resistant tumors

STCube, ‘BTN1A1 shows efficacy in PD-L1–negative, PD-1 resistant tumors’

STCube CSO Seung-han Yoo and Professor Soo-hyeon Lee (Korea University Anam Hospital)

BTN1A1-based investigator-initiated trial results unveiled at ESMO 2025

Biomarker-based treatment strategies seek to overcome limitations of PD-1 inhibitors

STCube is venturing into one of immuno-oncology’s uncharted territories.

 

The company has been exploring therapeutic responses of its first-in-class BTN1A1-targeting drug candidate, Nelmastobart, in patients with PD-L1–negative or PD-1-resistant tumors, marking the first step toward realizing precision immunotherapy.

 

At the European Society for Medical Oncology (ESMO) 2025 Congress, STCube presented two studies: an investigator-initiated trial and a preclinical study.

 

The investigator-initiated trial demonstrated a correlation between BTN1A1 expression levels and progression-free survival, while the preclinical study showed the complementary effect of BTN1A1 inhibition when combined with chemotherapy.

 

Dailypharm met with Seung-han Yoo, Chief Scientific Officer (CSO) of STCube, and Soo-hyeon Lee, Professor of Medical Oncology at Korea University Anam Hospital, in Berlin to discuss the significance of the research and future plans.

 

Poster Presentation by Professor Soo-hyeon Lee (Korea University Anam Hospital)

“Efficacy observed in PD-L1–negative patients, new potential found for precision immunotherapy” According to the company, BTN1A1 is a target first identified globally by STCube and is an immune checkpoint protein that acts independently of PD-L1.

 

BTN1A1 shows minimal expression in normal tissues but high expression in tumor cells, making it both a therapeutic target and a potential predictive biomarker.

 

CSO Yoo explained, “BTN1A1 is highly expressed in tumors where PD-L1 is rarely expressed, particularly colorectal cancer and non-small cell lung cancers.

 

It has the potential to open a new response pathway in patient groups unresponsive to existing immune checkpoint inhibitors.” The ESMO presentation featured interim analysis results from an ongoing Phase 1b/2 investigator-initiated clinical trial for metastatic colorectal cancer at Korea University Anam Hospital, focusing on differences in progression-free survival by degree of BTN1A1 expression.

 

The preclinical poster confirmed that BTN1A1 expression actually increases after chemotherapy.

 

CSO Yoo stated, “Unlike how PD-L1 is primarily expressed in rapidly growing tumor cells, BTN1A1 is highly expressed in slow-growing cells that remain after treatment—specifically, dormant tumor cells.

 

This allows for a complementary effect when combined with chemotherapy.” He added, “In the study, tumor suppression was significantly enhanced when BTN1A1 inhibitors were co-administered with standard anticancer drugs like FOLFOX (folinic acid + fluorouracil + oxaliplatin) and FOLFIRI (folinic acid + fluorouracil + irinotecan) for colorectal cancer, FOLFIRI for lung cancer, and docetaxel for lung cancer.

 

The findings suggest we could consider adopting a combination strategy for patients resistant to PD-1 inhibitors.” “Extends revival in BTN1A1-High patients...

 

will acclerate biomarker clinical trials” A correlation between BTN1A1 expression levels and clinical response was also observed in the ongoing colorectal cancer investigator-initiated clinical trial (Phase 1b/2) at Korea University Anam Hospital.

 

STCube CSO Seung-han Yoo

CSO Yoo, analyzed, “The higher the BTN1A1 expression, the more pronounced the response.

 

The median progression-free survival (mPFS) was 6.3 months in the patient group with a BTN1A1 H-Score of 250 or higher, 4.2 months in the 150-249 group, and 4.0 months in the group below 150.” These results represent an improvement over the average 2-3 months seen with existing standard third-line therapies.

 

Based on this, the company is actively advancing its biomarker-based clinical strategy targeting BTN1A1-positive patients and is preparing to initiate dosing in its company-led Phase II trial for non-small cell lung cancer by the end of this year.

 

On this day, Professor Lee summarized the clinical significance of the BTN1A1 inhibitor into four points, in addition to the explanation provided by CSO Yoo.

 

“It presents new possibilities for cancer types unresponsive to existing PD-1-centric therapies and can serve as a combination partner for PD-1-resistant or refractory patients.

 

Alongside the significance of biomarker-based clinical design, its minimal toxicity when combined positions it to evolve into a safe immuno-oncology platform.” Professor Lee further evaluated, “While PD-1 combination therapy can sometimes cause unexpected immune-related adverse reactions, BTN1A1 inhibitors do not add toxicity when combined with existing drugs.

 

In fact, their high safety profile makes them suitable as new combination partners.” Lee added that no immune-related adverse reactions were reported in actual patient administration, but noted that confirming long-term and large-scale safety remains a subsequent task.

 

“Will build data and explore global collaboration… to realize precision immunotherapy” The company plans to use these results as clinical evidence for its BTN1A1-based precision immunotherapy platform and accelerate the expansion of its subsequent pipeline.

 

Specifically, it intends to secure additional clinical data for colorectal and lung cancer by early next year and then formally initiate technology transfer discussions with global pharmaceutical companies.

 

In the long term, the strategy is to build a precision immunotherapy portfolio centered on BTN1A1 inhibitors to address unmet needs in the post-PD-1 market.

 

CSO Yoo added, “BTN1A1 could be the missing link explaining immune responses not accounted for by PD-L1.

 

We will work step-by-step to demonstrate the potential of precision immuno-oncology through clinical data.”