SAIL66 / Roche - LARVOL DELTA

CLDN6 Expression Plasticity in Ovarian Cancer: Insights into Therapeutic Optimization for CLDN6-Targeted Immunotherapy. (PubMed, Cancer Res Commun) - "Post-carboplatin analysis revealed increased CLDN6 expression, EMT-related gene changes, and enhanced T-cell infiltration, which were associated with the synergistic effect of SAIL66. Our study provides insights into the biology and plasticity of CLDN6-positive cells in EOC heterogeneity and highlights the clinical significance of CLDN6-targeting therapies for ovarian cancer treatment."

IO biomarker • Journal • Epithelial Ovarian Cancer • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • CLDN6

Progress made in R&D activities during the period from January 1, 2025 to December 31, 2025 was as follows. (Chugai Press Release) - "We made a management decision to discontinue the in-house development of a RAS inhibitor LUNA18, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-CD137 agonistic switch antibody STA551, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-latent TGF-β1 monoclonal antibody SOF10, considering obtained data up to date and the portfolio status. We made a management decision to discontinue the in-house development of an anti-CLDN6/CD3/CD137 trispecific antibody SAIL66, considering obtained data up to date and the portfolio status."

Discontinued • Gastric Cancer • Non Small Cell Lung Cancer • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thoracic Cancer

A Phase 1 Study of SAIL66 in Patients With CLDN6-positive Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=231 | Active, not recruiting | Sponsor: Chugai Pharmaceutical | Recruiting ➔ Active, not recruiting

Enrollment closed • Solid Tumor • CLDN6

A Phase 1 Study of SAIL66 in Patients With CLDN6-positive Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=231 | Recruiting | Sponsor: Chugai Pharmaceutical | Trial completion date: Dec 2028 ➔ Oct 2029 | Trial primary completion date: Dec 2028 ➔ Oct 2029

Trial completion date • Trial primary completion date • Oncology • Solid Tumor • CLDN6

Chugai’s SAIL66, under Development for CLDN6 Positive Solid Tumors, Non-Clinical Research Results Published in the Journal for ImmunoTherapy of Cancer (Chugai Press Release) - "The following findings were demonstrated in this research, which suggest that SAIL66 may be useful as a treatment for CLDN6 positive solid tumors...Creation of SAIL66, which is a novel tri-specific T-cell engager (TCE) for Claudin-6 (CLDN6), CD3, and CD137, applying Dual-Ig®technology, Chugai’s proprietary antibody engineering technology; SAIL66 binds to CLDN6, which is specifically expressed on tumor tissue, and does not bind to other CLDN family proteins (CLDN3, 4, or 9) with similar amino sequences; in vitro, SAIL66 was shown to strongly activate T cells and exert cancer cell cytotoxicity by not only triggering CD3 signaling like conventional TCEs, but also by providing CD137 co-stimulation."

Preclinical • Solid Tumor

SAIL66, a next generation CLDN6-targeting T-cell engager, demonstrates potent antitumor efficacy through dual binding to CD3/CD137. (PubMed, J Immunother Cancer) - "Our data demonstrate that SAIL66, designed to engage CLDN6, CD3, and CD137, has the potential to enhance antitumor activity and provide a potent therapeutic option for patients with ovarian and other solid tumors expressing CLDN6. Clinical trials are currently underway to evaluate the safety and efficacy of SAIL66."

IO biomarker • Journal • Oncology • Ovarian Cancer • Solid Tumor • CD4 • CD8 • CLDN6 • TNFRSF9

CLDN6: Biological insight into therapeutic potency of SAIL66, a next generation of T-cell engager targeting CLDN6 (AACR 2024) - P1 | "As a result, significant tumor regression was observed in mice treated with SAIL66 in combination with carboplatin.Conclusion and Ovarian cancer is characterized by significant tumor heterogeneity. In a HuNOG tumor-bearing mouse model transplanted with CLDN6-positive ovarian cancer cells (OV90, OVCAR3), SAIL66 showed potent antitumor activity as a single agent. Surprisingly, CLDN6 expression in transplanted tumors was significantly lower compared to in vitro cultured cells, suggesting that CLDN6 expression is highly variable. In vitro, CLDN6 expression reversibly fluctuated depending on cell density, and its expression was consistent with the expression of epithelial-mesenchymal transition (EMT) and stemness-related genes."

IO biomarker • Oncology • Ovarian Cancer • Solid Tumor • CLDN6 • TNFRSF9

SAIL66, a next generation T cell engager targeting CLDN6, potentiates efficacy by binding to CD3/CD137 (AACR 2024) - P1 | "To enhance immune activation and achieve successful clinical outcomes against solid tumors expressing CLDN6, we generated SAIL66, a CLDN6-targeting next generation TCE, using a new technological format called Dual-Ig®. SAIL66 is a tri-specific monoclonal antibody designed to bind to CLDN6 on cancer cells with one Fab arm and to both CD3 and CD137 with the other Fab arm. The preclinical characterization of SAIL66 was performed in a series of in vitro and in vivo studies which included comparisons to a conventional TCE targeting CLDN6 and CD3."

Clinical • IO biomarker • Oncology • Solid Tumor • CLDN3 • CLDN4 • CLDN6 • TNFRSF9

SAIL66, a next generation of T cell engager targeting CLDN6, potentiates efficacy (SITC 2023) - P1 | "Conclusions SAIL66 offers a novel therapeutic option by incorporating CD137 co-stimulatory signaling in addition to CD3 signaling for the treatment of patients with cancer expressing CLDN6. Clinical studies of SAIL66 are currently underway for patients with solid cancer (NCT05735366)."

Clinical • IO biomarker • Oncology • Solid Tumor • CLDN3 • CLDN4 • CLDN6 • TNFRSF9

A Phase 1 Study of SAIL66 in Patients With CLDN6-positive Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=178 | Recruiting | Sponsor: Chugai Pharmaceutical | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Oncology • Solid Tumor • CLDN6

A Phase 1 Study of SAIL66 in Patients With CLDN6-positive Locally Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=178 | Not yet recruiting | Sponsor: Chugai Pharmaceutical

Metastases • New P1 trial • Oncology • Solid Tumor • CLDN6