Ascendis files IND for sustained-release, anti-cancer TLR drug

FDA Building 2
Resiquimod could activate intratumoral antigen presenting cells and induce immune stimulatory cytokines. (FDA)

Ascendis Pharma has filed to run a clinical trial of an intratumoral, sustained-release formulation of resiquimod. The TLR agonist has shown preclinical promise as a cancer therapy, but its clinical use has been held back by tolerance, poor solubility and adverse effects associated with systemic delivery.

Denmark’s Ascendis has applied its TransCon platform to the molecule to address the barriers to use. The technology connects an unmodified drug to an inert carrier via a temporary linker. When bound to the carrier, the drug is inactive and shielded from clearance. The link between the drug and carrier gradually breaks down in the body, driving the steady release of the therapeutic molecule.

Ascendis validated the technology with TransCon hGH, a prodrug of human growth hormone that has a PDUFA action date of June 25. If approved, TransCon hGH could challenge Pfizer’s Genotropin and its near-approval successor somatrogon for the pediatric growth hormone deficiency market.

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With TransCon hGH nearing approval, Ascendis is expanding beyond the rare endocrinology diseases that have served as a proving ground for its technology. The IND filing for TransCon TLR7/8 Agonist is a key step in that process.

The filing, the first oncology IND from Ascendis, moves the company toward the initiation of a clinical trial of its intratumoral, sustained-release formulation of resiquimod. Ascendis designed the therapy to release resiquimod for several weeks following a single injection. By injecting the therapy into the tumor, Ascendis expects to see minimal systemic exposure to resiquimod.

In theory, the sustained exposure of tumor cells to resiquimod, coupled with minimal presence of the drug in healthy tissues, could enable Ascendis to activate intratumoral antigen-presenting cells and induce immune stimulatory cytokines without causing intolerable systemic adverse events.

Other researchers have come at the barriers to systemic use of resiquimod from different angles, including through nanoparticle encapsulation. The work has generated evidence that resiquimod is complementary to PD-1 checkpoint inhibitors.