On November 6, 2018 Immune Design (Nasdaq: IMDZ), an immunotherapy company focused on next-generation therapies in oncology, reported multiple presentations showcasing G100, its potent intratumoral TLR4 agonist, at the annual meeting for the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) being held in Washington D.C. this week (Press release, Immune Design, NOV 6, 2018, View Source [SID1234530792]). The presentations, which include both clinical and preclinical study data, further support the activity of G100 in follicular lymphoma patients and the potential combinability of G100 with other novel immune-modulatory agents.

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"These additional positive clinical data continue to support the ability of G100 to trigger a systemic therapeutic effect when injected into a single tumor in follicular lymphoma patients," said Carlos Paya, M.D., President and Chief Executive Officer of Immune Design. "In addition, we are pleased to observe that G100 can be synergistic with novel therapies such as anti-OX40 antibodies and adoptive T-cell therapies."

Key data to be presented:

The higher dose (20ug) of intratumorally-administered G100 is active, as determined by clinical outcomes and increased biomarker activity in patients with follicular lymphoma

Data from a new cohort of 18 follicular lymphoma patients treated with G100 at 20ug with low-dose radiation further confirms that G100 is active in the absence of an anti-PD-1 antibody and continues to have a favorable safety profile.
Comparison of data from these 18 patients treated with G100 at 20ug versus data from 16 patients previously treated with 10ug shows:
Positive trend toward more rapid overall clinical responses, including in abscopal (untreated) lesions.
Increased TILs and decreased lymphoma-associated CD20 cells in tumors following G100 treatment, which are biomarkers previously associated with improved clinical responses.
Higher ORR (60%) is observed in patients stratified by baseline tumor high TLR4 expression.
Consistently favorable safety profile.
Based on these positive data, Immune Design has selected the 20ug dose of G100 for further clinical development.

Synergistic anti-tumor effects of G100 with anti-OX40 antibodies

Combination of intratumoral G100 and systemic anti-OX40 monoclonal antibody is synergistic in aggressive lymphoma and melanoma preclinical models.
Improved anti-tumor activity in comparison to either agent alone.
Increased biomarker levels that correlate with effectiveness, such as TILs and the ratio of CD8/CD4 tumor-specific T cells.

G100 enhances the efficacy of adoptive T-cell therapy

Combination of intratumoral injection of G100 and adoptive T-cell therapy was found to be synergistic in pre-clinical tumor models.
Tumor eradication observed in 70% of mice treated compared to no tumor regression with either approach alone.
Median survival was significantly improved with the combination regimen.
About G100

G100 is Immune Design’s lead product candidate and contains a potent synthetic small molecule toll-like receptor-4 (TLR-4) agonist called Glucopyranosyl Lipid A (GLA). G100 activates innate and adaptive immunity in the tumor microenvironment to generate an immune response against the tumor’s preexisting diverse set of antigens. A growing set of clinical and preclinical data have demonstrated the ability of G100 to activate tumor-infiltrating lymphocytes, macrophages and dendritic cells, and promote antigen-presentation and the recruitment of T cells to the tumor. The induction of local and systemic immune responses has been shown to result in local and abscopal (shrinking of tumors outside the scope of the localized treatment) tumor control. G100 is currently in development to treat patients with relapsed follicular lymphoma (FL), a sub-type of Non-Hodgkin lymphoma. Immune Design intends to start a study in earlier-stage lymphoma patients in combination with rituximab, a standard treatment for lymphomas, and is evaluating studies in other B-cell malignancies beyond FL, as well as potential solid tumor indications