Oncolytic Adenovirus in Phase 1 has extended half-life TGF-ß trap
La Jolla, Calif., Dec. 8, 2021 – EpicentRx, Inc., a clinical-stage biotechnology company at the forefront of oncolytic viruses and small molecules for the treatment of cancer and other inflammatory-driven diseases, today announced publication of an original article entitled “Toxicology and biodistribution of AdAPT-001, a replication-competent type 5 adenovirus with a trap for the immunosuppressive cytokine, TGF-beta” in the American Journal of Cancer Research issue 2156-6976. Click here to access the article online.
This article presents proof-of-concept preclinical data on the biodistribution and toxicity of single dose AdAPT-001 administration in tumor bearing animals and its demonstration of long-term TGF-β trap persistence in the serum over the length of a 14-day study after intravenous and intratumoral administration in the absence of TGF-β trap-related toxicity. This confirmation of the long serum half-life of the TGF-β trap bolsters clinical confidence that even one dose of AdAPT-001 may demonstrate prolonged activity in patients.
AdAPT-001 is a cancer-targeting genetically modified adenovirus armed with an inserted TGF-β trap under investigation in an ongoing Phase 1 clinical trial called BETA PRIME (ClinicalTrials.gov Identifier: NCT04673942), so-named because it elicits adaptive T cell responses.
The TGF-β trap is an extended half-life decoy receptor that binds to TGF-β and counteracts its immunosuppressive effects. To date, in the first-in-human BETA PRIME study, all single AdAPT-001 doses have been well tolerated and no drug-related adverse events have been observed in accord with preclinical data. Study enrollment is ongoing.
The second part of the BETA PRIME study, for which enrollment has not yet begun, will involve repeat AdAPT-001 dosing and expand to include combination with an immune checkpoint inhibitor (ICI). According to the hypothesis of the study, the TGF-β trap will render tumor cells susceptible to ICIs even if they were previously non-responsive since abnormal TGF-β signaling contributes to immune checkpoint inhibitor resistance.
“Of the several strategies that have been developed and evaluated to inhibit TGF-β in clinical trials, namely monoclonal, neutralizing, and bifunctional antibodies, antisense oligonucleotides, TGFβ-related vaccines, and receptor kinase inhibitors, AdAPT-001 may be the most potent of all,” said Tony R. Reid, M.D., Ph.D., Chief Executive Officer of EpicentRx. “Its combination virotherapy and gene therapy approach creates a kind of positive feedback loop where the TGF-β trap dose is amplified by replication of the virus and the TGF-β amplifies the antitumor activity of the virotherapy.”
AdAPT-001 is an oncolytic virus which is part of the company’s proprietary AdAPT Immunotherapy Platform, a platform developed on a genetically modified version of the human adenovirus that has been uniquely designed to preferentially infect and kill cancer cells. Currently in an ongoing Phase 1 trial for solid tumors, AdAPT-001 encodes a ligand trap comprised of the ligand-binding domain of the TGF-β receptor, which is fused to the portion of the human antibody known as the Fc domain.
About EpicentRx, Inc.
EpicentRx is a leading-edge biopharmaceutical company with a complementary pipeline of small molecule and cancer targeting virus platforms that represent the next frontier in treating patients with diseases of significant unmet need. With two platforms, CyNRGY and AdAPT, EpicentRx has developed novel therapies and drug delivery devices with emphasis on not just treating the disease but improving quality of life. For more information, visit www.epicentrx.com.