nelmastobart (STT-003) / STCube Pharma - LARVOL DELTA

STCube Announces…Preclinical Results of BTN1A1-YAP1-Based Immuno-Oncology at AACR [Google translation] (HIT News) - "In the second poster, we presented the results of a 3D spheroid model experiment targeting colon cancer and lung cancer cell lines. The study contained the content that co-expression of BTN1A1 and YAP1 acts as a mechanism of anticancer drug resistance and that this can be inhibited by BTN1A1 inhibition....According to the company, the experiment confirmed that BTN1A1 inhibition reduces YAP1-related resistance and induces a T cell-driven immune response as a mechanism of action. Nelmastobart showed a strong anti-tumor effect when used in combination with TAS-102 (colon cancer) and docetaxel (lung cancer), and showed a significant effect especially in a resistant model in which YAP1 was overexpressed."

Preclinical • Colon Cancer • Lung Cancer

STCube Announces…Clinical Results of BTN1A1-YAP1-Based Immuno-Oncology at AACR [Google translation] (HIT News) - P1b/2 | N=59 | NCT05990543 | "In the first poster presentation, the results of the investigator-led phase 1b clinical trial targeting patients with metastatic colorectal cancer were introduced. This trial evaluated the efficacy and safety of the combination of nelmastobarb and capecitabine in patients with MSS colorectal cancer who had received three or more lines of treatment. Of the total 12 patients, 2 had a partial response (PR) and 10 had stable disease (SD), resulting in an objective response rate (ORR) of 17% and a disease control rate (DCR) of 100%. A follow-up phase 2 clinical trial is currently underway with 39 patients and is currently in the follow-up phase....Analysis of the correlation between clinical response and BTN1A1 expression showed that BTN1A1 expression was highest in the patient group that showed PR, and the expression level tended to be low in the patient group with SD or disease progression."

P1 data • Colorectal Cancer

BTN1A1 and YAP1 crosstalk: A key mechanism in tumor immune evasion and therapeutic targeting (AACR 2025) - "A549lung cancer cell lines were labeled and cultured as 3D spheroids with human peripheral bloodmononuclear cells (hPBMC), hSTC810, and docetaxel...Similarly, LS1034 colon cancer celllines were labeled and cultured as 3D spheroids with hPBMC, hSTC810, and TAS-102...By simultaneously downregulating YAP1-driven oncogenic pathways andenhancing immune activation, BTN1A1 inhibition offers a novel dual mechanism for combatinglung and colon cancers. These findings pave the way for future clinical exploration of BTN1A1as a key target in cancer immunotherapy."

IO biomarker • Late-breaking abstract • Colon Cancer • Colorectal Cancer • Lung Cancer • Oncology • Solid Tumor • BTN1A1 • YAP1

BTN1A1 and YAP1 expression as biomarkers in colon cancer: Phase 1b trial results of hSTC810 (AACR 2025) - "The subsequent Phase 1b/2 trial investigating BTN1A1 inhibition in combination with chemotherapy is currently ongoing. Colon cancer patients were enrolled in the study and treated with hSTC810 in combination with capecitabine to evaluate the efficacy and safety of the combination therapy. Findings from this Phase 1b trial suggest that targeting BTN1A1 with hSTC810 is a safe and promising therapeutic strategy for colon cancer, particularly in patients with highYAP1 expression. These results support further investigation in larger, randomized trials to confirm the efficacy and biomarker-driven utility of hSTC810 in colon cancer therapy."

Biomarker • Late-breaking abstract • P1 data • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BTN1A1 • YAP1

STCube introduces research results on BTN1A1, a new biomarker for colon cancer, at AACR [Google translation] (BioTimes) - "STCube announced on the 26th that it will present two abstracts at the '2025 American Association for Cancer Research Annual Meeting (AACR 2025)' to be held in Chicago, USA from April 25th to 30th....The STCube research team confirmed that BTN1A1 and YAP1 interact and co-localize in various solid cancers, and that YAP1 activates immune evasion function by inducing BTN1A1 expression. BTN1A1 was found to not only regulate the immune function of T cells, but also play an important role in the expression and activation of YAP1. STCube confirmed the therapeutic effect in colon cancer cell lines (combination therapy with nelmastovar and TAS-102) and lung cancer cell lines (combination therapy with nelmastovar and docetaxel) through 3D spheroid experiments."

Biomarker • Preclinical • Colon Cancer • Lung Cancer

STCube receives IND approval for nelmastobart in metastatic colorectal cancer in Korea (Korea Biomedical Review) - "STCube said Thursday it received approval from the Ministry of Food and Drug Safety (MFDS) for its investigational new drug (IND) application to initiate a phase 1b/2 clinical trial of nelmastobart, a novel immune checkpoint inhibitor targeting BTN1A1, in patients with metastatic colorectal cancer....The trial will be conducted at five university hospitals across Korea, with Institutional Review Board (IRB) review already underway at Korea University Anam Hospital. STCube plans to promptly submit IRB applications to the remaining hospitals to accelerate the clinical process. The study will evaluate the safety and efficacy of nelmastobart in combination with TAS-102 and bevacizumab in patients with metastatic or recurrent colorectal cancer who are refractory or intolerant to oxaliplatin- and irinotecan-based chemotherapy."

Trial status • Colorectal Cancer

Nelmastobart in Combination with Trifluridine/Tipiracil and Bevacizumab in Metastatic/Recurrent Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=70 | Not yet recruiting | Sponsor: STCube, Inc.

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor

STCube, Colorectal Cancer Phase 1b/2 IND Submission to MFDS… Biomarker-based Clinical Trial Promotion [Google translation] (HIT News) - "STCube announced on the 18th through a public disclosure that it had submitted a phase 1b/2 clinical trial plan (IND) for the treatment of metastatic colorectal cancer with the next-generation immunotherapy drug 'Nelmastobart' to the Ministry of Food and Drug Safety....According to the company, this clinical trial will be conducted on patients with metastatic or recurrent colorectal cancer who are refractory or intolerant to oxaliplatin and irinotecan-based chemotherapy. It will evaluate the efficacy and safety by adding nelmastobart to the standard treatment, trifluridine/tipiracil (TAS-102) and bevacizumab combination therapy. The company said it will be conducted at five university hospitals in Korea, including Korea University Anam Hospital."

New P1/2 trial • Colorectal Cancer

BTN1A1 expression in colon cancer: Implications for immunotherapy and patient stratification. (ASCO-GI 2025) - P1 | "Recently, Nelmastobart, an antibody targeting BTN1A1, successfully completed a Phase 1 clinical trial at three sites in the United States and two in the Republic of Korea, spanning 98 weeks... This Phase 1 clinical trial demonstrated that antibody-mediated BTN1A1 blockade effectively suppresses tumor growth in patients with BTN1A1-positive CRC. These findings suggest that BTN1A1-targeted therapies could provide a viable treatment option for patients with colon cancers that are refractory or resistant to anti-PD-1/PD-L1 therapies."

Clinical • IO biomarker • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BTN1A1

Nelmastobart (hSTC810) combined with capecitabine therapy in metastatic colorectal cancer with resistance or intolerance to oxaliplatin and irinotecan-based chemotherapy: A phase 1b clinical trial. (ASCO-GI 2025) - "The combination of hSTC810 and capecitabine is well tolerated at the MTD, without unexpected AEs and shows promising antitumor activity in patients with heavily treated mCRC. The phase 2 study is currently in progress."

Clinical • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BTN1A1

STCube, Colon Cancer Treatment Clinical Phase 1b Clinical Trial Proves Improved Survival Rate [Google translation] (HIT News) - P1b/2 | N=59 | NCT05990543 | "STCube explained that the research team...will present...at the 'ASCO GI 2025...According to the company, the safety evaluation results of Phase 1b showed that no unexpected adverse reactions were observed in patients with advanced metastatic colorectal cancer with nelmastobart combination therapy...The objective response rate (ORR) of the efficacy evaluation results was 17%, with 2 out of 12 patients reporting partial response (PR). The clinical benefit rate (CBR) at 16 weeks (4 months) was 66.7% (8/12 patients), and the mPFS of 4.4 months was achieved at the time of the abstract data cutoff....STCube announced that it is preparing to apply for a colorectal cancer clinical trial (SIT, company-led clinical trial) of nelmastobart in the first quarter of this year..."

New trial • P1 data • Colon Cancer • Colorectal Cancer

STCube to Participate in ASCO GI Next Month… Announcement of Colon Cancer Immunotherapy Treatment Strategy [Google translation] (BioTimes) - "STCube announced on the 27th that two research abstracts on 'Nelmastobart (hSTC810)' were accepted for poster presentation at ASCO GI 2025. At this conference, Stephen Yoo...will present on ‘BTN1A1 expression in colon cancer: Implications for immunotherapy and patient stratification’. The results of this study suggest that BTN1A1-targeted therapy can enhance the response to immunotherapy in colon cancer. In addition, Professor Lee Soo-hyun...will present on the topic of 'Nelmastobart (hSTC810) combined with capecitabine therapy in metastatic colorectal cancer with resistance or intolerance to oxaliplatin and irinotecan-based chemotherapy: A phase 1b clinical trial."

Clinical data • Colon Cancer • Colorectal Cancer

STCube to Participate in ’JP Morgan Healthcare Conference’… “Planning to Negotiate Technology Exports“ [Google translation] (BioTimes) - "STCube announced on the 9th that it will be having business meetings with several global top big pharmas at JP Morgan in January next year for the technology export of 'Nelmastobart '. Nelmastobart is a first-in-class (first within the group) BTN1A1 target immune checkpoint inhibitor, which is STCube's main pipeline....STCube plans to expand the indications of Nelmastobart starting with colorectal cancer and small cell lung cancer."

Clinical • Colorectal Cancer • Small Cell Lung Cancer

STCube, Phase 2a Clinical Trial for Terminal Small Cell Lung Cancer Confirms Partial Response in 2 Out of 3 Patients [Google translation] (BioTimes) - P1b/2a | N=130 | NCT06016270 | Sponsor: STCube, Inc. | "On the 18th, STCube announced that out of the three patients who underwent tumor evaluation in the phase 2a clinical trial of Nelmastobart, an anti-BTN1A1 immune checkpoint inhibitor, two had partial remissions (PR) and one had stable disease (SD), demonstrating high anticancer efficacy....No dose-limiting toxicity (DLT) or maximum tolerated dose (MTD) was observed at any dose, suggesting that combination therapy with nelmastobart, which inhibits BTN1A1, will create a new history in the treatment of intractable cancer."

P2a data • Small Cell Lung Cancer

A phase I study of hSTC810 (Nelmastobart), an anti-BTN1A1 antibody, in patients with advanced solid tumors (SITC 2024) - "A copy of the letter of approval and the IRB/IEC membership roster were received by the Sponsor prior to any drug shipment. 2 Ethical Conduct of the Study The study was conducted in accordance with the Declaration of Helsinki and with all applicable laws and regulations of the locale and country where the study was conducted, and in compliance with Good Clinical Practice Guidelines."

Clinical • Late-breaking abstract • Metastases • P1 data • Biliary Cancer • Breast Cancer • Cholangiocarcinoma • Colorectal Cancer • Lung Cancer • Melanoma • Microsatellite Instability • Oncology • Solid Tumor • BTN1A1 • MSI

Spatial biology insights into simultaneous targeting of BTN1A1 and YAP in cancer: enhanced efficacy in 3D cultures and mouse models (SITC 2024) - "This phenomenon was confirmed in organoid and mouse models, and Opal multiplex immunofluorescence analysis showed that hSTC810 treatment effectively eliminated normal and YAP1-positive tumors. Conclusions In vitro and in vivo data demonstrate that YAP increases the expression of BTN1A1. Our study suggests that anti-BTN1A1 treatment may serve as a novel immune checkpoint to overcome antitumor resistance in tumors prone to resistance."

IO biomarker • Preclinical • Oncology • BTN1A1 • PD-L1 • YAP1

Development and efficacy of a bispecific antibody targeting BTN1A1 and PD-L1 in cancer immunotherapy (SITC 2024) - "Conclusions In vitro and in vivo data show that treatment with bispecific antibodies (hSTC810 and anti-PD-L1) significantly enhances antitumor activity compared to treatment alone. Our findings suggest that this represents a new immune checkpoint capable of overcoming antitumor resistance by targeting a broad spectrum of colon cancers using bispecific antibodies."

Clinical • IO biomarker • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BTN1A1

STCube Announces Clinical Results of Nelmastobart at SITC 2024 [Google translation] (Medipana) - "STCube, a developer of immuno-oncology drugs, announced on the 7th that it will be presenting a poster on the dual mechanism of action of BTN1A1 and the updated clinical analysis results of the anti-BTN1A1 immune checkpoint inhibitor Nelmastobart at the 'Society for Immuno-Oncology Conference (SITC 2024)' in November....The regular abstract topic of STCube is 'Spatial Biology Insights into Simultaneous Targeting of BTN1A1 and YAP in Cancer' and it is about the dual mechanism of action of BTN1A1."

Clinical data • Oncology

STCube, Metastatic Colorectal Cancer Researcher Confirms Excellent Anticancer Effect in Phase 1b [Google translation] (BioTimes) - P1b | N=59 | NCT05990543 | "STCube...announced...the phase 1b patient administration of the phase 1b/2 clinical trial of 'Nelmastobart', a colon cancer researcher-led trial, has been completed. As the phase 2 clinical trial is expected to proceed quickly as the improvement effect exceeding the existing standard treatment has been confirmed in the patient group administered the drug...all 12 phase 1b patients are undergoing administration and follow-up observation. The recommended phase 2 dose (RP2D) of the clinical trial was selected as nelmastobart 800 mg and capecitabine 1000 mg/m2, which are expected to have no adverse drug reactions and high efficacy...Phase 2 will recruit 39 patients and is scheduled to begin dosing soon. The primary endpoint of Phase 1b/2 is progression-free survival (PFS) in the nelmastobart and capecitabine combination group....'the patient registration rate is high, so phase 2 is expected to proceed quickly in the second half of the year.'"

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of hSTC810 With Advanced/Metastatic Solid Tumors (STCUBE-001) (clinicaltrials.gov) - P1 | N=47 | Completed | Sponsor: STCube, Inc. | Active, not recruiting ➔ Completed | Trial completion date: Aug 2024 ➔ Feb 2024

Metastases • Monotherapy • Trial completion • Trial completion date • Oncology • Solid Tumor

Combination of hSTC810 and capecitabine therapy in metastatic colorectal cancer with resistance or intolerance to oxaliplatin and irinotecan-based chemotherapy: A single arm, phase 1b/2, multicenter study. (ASCO-GI 2024) - P1b/2 | "BTN1A1 has been shown to inhibit anti-CD3-induced cytokine production and T-cell proliferation and also inhibit anti-CD3-induced p38 mitogen-activated protein kinase (MAPK), cAMP response element-binding protein (CREB) and target of rapamycin (TOR) phosphorylation in human T-cells. An exploratory study is underway to investigate the impact of hSTC810 on the tumor microenvironment and cytokines, utilizing both tissue biopsies and blood sampling. Clinical trial information: NCT05990543."

Clinical • IO biomarker • Metastases • P1/2 data • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A Study of hSTC810 in Combination With Paclitaxel in Relapsed or Refractory Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=130 | Recruiting | Sponsor: STCube, Inc. | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

A Study of hSTC810 With Advanced/Metastatic Solid Tumors (STCUBE-001) (clinicaltrials.gov) - P1 | N=66 | Active, not recruiting | Sponsor: STCube, Inc.

Metastases • Monotherapy • Trial completion date • Trial primary completion date • Oncology • Solid Tumor

A Study of hSTC810 With Advanced/Metastatic Solid Tumors (STCUBE-001) (clinicaltrials.gov) - P1 | N=66 | Active, not recruiting | Sponsor: STCube, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

BTN1A1-Targeted Immunotherapy Combined with Standard Therapy in Small Cell Lung Cancer (SCLC) and Colorectal Cancer (SITC 2023) - "The organoids were examined for morphologic disruption following hPBMC, hSTC810, and Paclitaxel treatment by assessing the organoid size and formation rate...Conclusions In vitro, in vivo, and clinical data show that hSTC810 treatment results in the activation of innate immune response pathways and enhances anti-tumor activity when combined with anti-PD-L1 therapy. Our results suggest that BTN1A1 is a novel immune checkpoint that can be targeted to overcome resistance to conventional therapies in SCLC patients."

IO biomarker • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • CD8