SD-101 is a proprietary investigational TLR9 agonist designed to elicit a potent and focused immune response to cancer, and provide multiple mechanisms of tumor killing.

SD-101 was specifically developed for cancer for highly efficient activation of the two principal TLR9 signaling pathways. One pathway leads to rapid Interferon-α production which in turn, stimulates a number of critical activities including activating natural killer cells, blocking tumor-mediated immune suppression, and promoting Th1 and CD8+ T cell homing into the tumor. The second pathway leads to efficient generation and activation of tumor-specific, cytotoxic CD8+ T cells. 

By delivering SD-101 directly into the tumor, we are focusing its activity on the injected tumors and its draining LN, which is intended to take advantage of high concentrations of tumor antigens that are present locally.  Notably, the cytotoxic CD8+ T cells generated in the SD-101 treated tumors have been observed to recognize and destroy both the injected tumor and distant tumor sites associated with metastatic disease. Additionally, the immune stimulation by SD-101 is not antigen specific and consequently, has the potential to be broadly effective in multiple tumor types.

Preclinical data support the use of TLR9 agonists in patients with solid tumors and hematologic malignancies. SD-101 has shown anti-tumor activities in multiple mouse tumor models alone and in combination with immune checkpoint inhibitors (e.g., anti-PD-1) (Wang, Campos et al. 2016; Sato-Kaneko F, Yao et al. 2017 Galotta, Assi et al 2018) 

In these models, the combination of SD-101 and PD-1 blockade result in improved expansion of highly functional cytotoxic T cells generated in the SD-101 injected tumor leading to a potentiated anti-tumor effect.

Clinical Program

Dynavax has an active clinical program developing SD-101 in a variety of cancer indications.  Two Phase 1 trials have been completed with SD-101 (Ribas, Medina et al. 2018 ; Frank, Reagan et al. 2018), which provided safety data and dose optimization for biological activity.  

Clinical Studies with SD-101 

SYNERGY-001 (DV3-MEL-01/Keynote 184)

On the basis of synergy observed in pre-clinical models studying the combination of SD-101 and anti-PD1 antibodies we are conducting a study of intratumoral SD-101 in combination with Keytruda®, an approved anti-PD-1 monoclonal antibody, in collaboration with Merck&Co., Kenilworth, NJ.

Title: A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Status: Recruiting

More information: Identifier NCT02521870


Investigator Sponsored Research

SD-101 is also being studied in novel combinations and additional tumor types by our academic collaborators.

Title: TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas

Status: Recruiting

More information: Identifier: NCT03410901

Title: TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma

Status: Recruiting

More information: Identifier NCT02927964

Title:   Phase I/II Trial of Epacadostat, Intralesional SD101, Radiotherapy in Patients With Lymphoma

Status: Recruiting

More information: Identifier NCT03322384  

Title:   Pembrolizumab in Combination With Intratumoral SD-101 Therapy

(patients with prostate cancer that has spread to other places in the body)

Status: Recruiting

More information: Identifier: NCT03007732