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 are able to focus cancer killing activities associated with TLR9 stimulation to the tumor and take advantage of high concentrations of tumor antigens from dying cells. This exposure to the tumor antigens generates 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 demonstrated anti-tumor activities in multiple mouse models alone and in combination with immune checkpoint inhibitors. These experiments have shown significant synergy between anti-PD-1 and SD-101. In addition to tumor volume reduction and improved survival rates, SD-101 greatly increases CD8+ T cell infiltration into tumors compared to anti-PD-1 alone.




Clinical Program

Dynavax is developing SD-101, a potent immune-stimulator, as a meaningful addition to the treatment of cancer patients. We believe this area will become increasingly dominated by combinations to improve response rates with checkpoint inhibitors and other standards of care, 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.

We are conducting a Phase 1/2 study (LYM-01) to assess the safety and proof of mechanism of intratumoral SD-101 in adults with untreated low-grade B-cell lymphoma in combination with low-dose radiation. LYM-01 is a dose escalation and expansion study where subjects receive treatment in a single radiated lesion. Data reported previously confirm the safety of SD-101 in a range of doses and its ability to elicit a systemic immune response as measured by local and abscopal (distant) tumor reductions over time. For additional information about LYM-01, please visit Identifier NCT02266147

In addition to LYM-01, SD-101 is currently being studied in combination with other agents in several ongoing clinical trials as outlined below.

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.

SD-101 and MK-1966

Merck & Co. is conducting a clinical study combining SD-101 and MK-1966, a monoclonal antibody against IL-10, in patients with advanced malignancies.

Title: A Phase 1/1b Trial of MK-1966 in Combination With SD-101 in Subjects With Advanced Malignancies

Status: Recruiting

More information: Identifier NCT02731742

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