SD-101 is a proprietary investigational TLR9 agonist designed to elicit a potent and focused immune response to cancer. By targeting TLR9 in both the early and late endosomes of plasmacytoid dendritic cells, SD-101 is intended to stimulate multiple mechanisms of tumor killing.

SD-101 was designed 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 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 can potentially focus cancer killing activities associated with TLR9 stimulation to the tumor and take advantage of high concentrations of tumor antigens from dying cells. Exposure to the tumor antigens can generate memory T cells that maintain long-lasting therapeutic effects. By stimulating the natural immune response SD-101 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 models alone and in combination with immune checkpoint inhibitors. These experiments suggest there could be synergies created between anti-PD-1 and SD-101. Based on data to date, SD-101 may increase CD8+ T cell infiltration into tumors compared to anti-PD-1 alone.




Clinical Program

Dynavax is developing SD-101, a TLR 9 agonist designed to stimulate the immune system, potentially generating an anti-tumor response in cancer patients. We believe combination therapies consisting of checkpoint inhibitors and other standards of care will become the primary method of treatment, and we are seeking to improve response rates without increasing toxicities.  SD-101 has completed two Phase 1 trials which provided safety data and dose optimization for biological activity. The Phase 1 studies also showed dose dependent increases in interferon induction in patients treated with SD-101.

Combination Drug Studies with SD-101

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 Phase 1b/2, Open-label, Multicenter, Dose Escalation and Expansion Trial of Intratumoral SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma

Objective:  To evaluate the safety, tolerability and preliminary efficacy of intratumoral SD-101 injections in combination with pembrolizumab in patients with advanced or metastatic melanoma.

Status: Recruiting

More information: Identifier NCT02521870

An expansion of this study into squamous cell head and neck cancer, a tumor type amenable to intratumoral injection, is planned.

Investigator Sponsored Research

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

Title: Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With Ibrutinib and Local Radiation in Relapsed or Refractory Low-Grade Follicular Lymphoma

Status: Recruiting

More information: Identifier: NCT02927964

Title: Phase 2 Trial Pembrolizumab or Pembrolizumab in Combination With Intratumoral SD-101 Therapy in Patients With Hormone-Naïve Oligometastatic Prostate Cancer Receiving Definitive Prostatic Radiation and Intermittent Androgen Deprivation Therapy

Status: Open, not yet recruiting

More information: Identifier NCT03007732