Study of Asgard’s new cancer immunotherapy modality demonstrates potent anti-tumor effects by turning tumor cells against themselves
New data “paves the way for first-in-human trials” of lead program AT-108, which is undergoing CMC development for GMP manufacturing
AT-108 is an off-the-shelf gene therapy that induces an immune response tailored against each unique patient’s cancer
LUND, Sweden, Sept. 5, 2024 /PRNewswire/ — Asgard Therapeutics, a privately held biotech company pioneering in vivo direct cell reprogramming for cancer immunotherapy, today announces the publication of key proof-of-concept data supporting its lead program, AT-108, in the high-impact, peer-reviewed journal, Science[1]. Novel data shows that AT-108 reprograms tumor cells, directly within the immunosuppressed tumor microenvironment, into an immunogenic cell fate, which mounts strong anti-tumor, antigen-specific responses and durable tumor shrinkage even upon metastatic rechallenge.
The study, co-led by Asgard Therapeutics and the Pereira Lab at Lund University, demonstrated efficient dendritic cell reprogramming in mouse models resistant to checkpoint blockade treatment and patient-derived tumor samples. The data provides preclinical proof-of-concept for an off-the-shelf, yet tumor-specific, first-in-class cancer immunotherapy, paving the way for first-in-human trials of AT-108. Reprogramming tumor cells so that they are converted into antigen-presenting dendritic cells “elicits systemic and long-term antitumor immunity,” stated the authors of the study. The study entitled, In vivo dendritic cell reprogramming for cancer immunotherapy, also shows the systematic selection of an optimal delivery system for expression of key reprogramming factors in the tumor, which led to the nomination of Asgard’s lead program.
Publication of the study follows Asgard’s €30 million Series A financing to advance its cell reprogramming platform, as the Company continues to make significant progress in preparing AT-108 for clinical development. Asgard recently commenced activities to establish CMC process for scale-up manufacturing of GMP-grade AT-108 for Phase I/II trials.
Cristiana Pires, Co-founder and Chief Executive Officer of Asgard Therapeutics, said: “This study demonstrates that Asgard’s platform converts tumor cells into dendritic cells within living organisms – and not just in vitro. This publication in such a high-impact journal as Science demonstrates the enormous potential of our cell reprogramming approach and the quality of our scientific methodology. Together with ongoing work to establish manufacturing process for lead program, AT-108, we are focused on completing IND-enabling studies, including pharmacokinetic and GLP toxicology studies, in advance of our near-term objective of filing a clinical trial application for testing of AT-108 in patients.”
Co-Lead author Fábio Rosa, PhD, Co-founder and Head of Research of Asgard Therapeutics, commented: “We are very pleased with the publication of this joint effort with Filipe Pereira and his team at Lund University, as it represents a significant milestone for the company ahead of clinical development. The new findings support the selection of a replication-deficient adenoviral vector for AT-108, demonstrating its proof-of-concept and prompting the start of advanced preclinical development. We were very excited to see that AT-108 induces complete tumor regressions and protects mice from tumor re-challenge – even in the metastatic setting.”
The reprogramming of tumor cells to cDC1-like cells restores tumor antigen presentation and remodels the tumor microenvironment, reducing exhausted and regulatory populations, and promoting infiltration and activation of cytotoxic T cells. Importantly, in vivo dendritic cell reprogramming induces complete responses as a monotherapy and synergizes with immune checkpoint blockade in aggressive immune-deserted tumor models. The finding of an abscopal effect on distant non-treated tumors highlights that benefits extend beyond the primary tumor.
Alongside the Pereira Lab from where the technology spun-out, Asgard collaborated with additional researchers at Lund University, Inge Marie Svane and Özcan Met from CCIT-DK, Denmark, and Irina Agarkova and team from InSphero, Switzerland to complete the study. The Company’s research has received support from Eurostars-2 Joint Program with co-funding from the European Union’s Horizon 2020 research and innovation program, Sweden’s Innovation Agency, E!115376 REPRINT Grant 2021-03371, and the Strategic innovation programs, Swelife.
Notes to Editors
About Asgard Therapeutics
Asgard Therapeutics is a privately held preclinical stage biotech company pioneering in vivo direct cell reprogramming for cancer immunotherapy. The company builds on ground-breaking and proprietary reprogramming technologies to develop gene therapy products designed to set in motion efficient and personalized immune responses. Backed by Johnson & Johnson Innovation – JJDC, Inc., RV Invest, Novo Holdings, Boehringer Ingelheim Venture Fund, and Industrifonden, Asgard Therapeutics aims to establish a pipeline of off-the shelf cancer immunotherapies that trigger personalized anti-cancer immune responses for the benefit of cancer patients in need. For more information, please visit: www.asgardthx.com.
About AT-108
AT-108 is a first-in-class, off-the-shelf gene therapy that directly reprograms tumor cells into a rare subset of dendritic cells critical for mounting efficient cytotoxic T cell responses, cDC1 cells (conventional dendritic cells type 1), which forces the tumor cells to present their tumor antigens, ultimately leading to a personalized anti-tumor immune response. It is based on a replication-deficient adenoviral vector that delivers three proprietary reprogramming factors into tumor cells, rewiring their gene expression signatures and thus “programming” them to become antigen-presenting cDC1-like cells.
1. http://www.science.org/doi/10.1126/science.adn9083
SOURCE Asgard Therapeutics
